Editorials
not allow this conclusion. Differences were minimal and the ICU mortality is not a sufficiently robust outcome measure, as influenced as it is by differences in discharge ICU policies and current trend toward earlier ICU discharge. As a more general reflection, we should consider if our insistence on prognostication models based on few variables recorded at an early stage of acute disease is worth the investment they require. In research, analysis of large datasets with multivariable models combining different features is needed to estimate prognosis (10). Yet, variations in outcome cannot be entirely explained even using sophisticated modeling of prognostic variables, which limits application of statistical prediction when decisions are made about early management (11). Probability estimates may help physicians and patients in deciding upon further management, if sufficient time is allocated to gain relevant prognostic information, to evaluate response to treatment (or lack thereof) and to consider patients’ values (12). But perhaps, paraphrasing Taleb (1, 2), “we should concentrate on the consequences of critical illness, which can be known (13, 14), rather than on the probability that they will occur, which can’t.”
REFERENCES
1. Samuel G: The perils of prediction. New York, The Economist, 2007. Available at: http://www.economist.com/node/9253918. Accessed September 28, 2014 2. Taleb NL: The Black Swan: The Impact of the Highly Improbable. Random House, 2007
3. Amos J: L’Aquila Quake: Italy Scientists Guilty of Manslaughter. BBC News, 2012. Available at: http://www.bbc.com/news/worldeurope-20025626. Accessed September 28, 2014 4. Teasdale GM, Nicoll JA, Murray G, et al: Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 1997; 350:1069–1071 5. Adhikari NK, Fowler RA, Bhagwanjee S, et al: Critical care and the global burden of critical illness in adults. Lancet 2010; 376:1339–1346 6. Gostin LO: Legal and ethical responsibilities following brain death: The McMath and Muñoz cases. JAMA 2014; 311:903–904 7. Wijdicks EFM, Kramer AA, Rohs T Jr, et al: Comparison of the Full Outline of UnResponsiveness Score and the Glasgow Coma Scale in Predicting Mortality in Critically Ill Patients. Crit Care Med 2015; 43:439–444 8. Sharshar T, Citerio G, Andrews PJ, et al: Neurological examination of critically ill patients: A pragmatic approach. Report of an ESICM expert panel. Intensive Care Med 2014; 40:484–495 9. Sharshar T, Porcher R, Siami S, et al; Paris-Ouest Study Group on Neurological Effect of Sedation (POSGNES): Brainstem responses can predict death and delirium in sedated patients in intensive care unit. Crit Care Med 2011; 39:1960–1967 10. Teasdale G, Maas A, Lecky F, et al: The Glasgow Coma Scale at 40 years: Standing the test of time. Lancet Neurol 2014; 13:844–854 11. Servadei F: Coma scales. Lancet 2006; 367:548–549 12. Downar J: Even without our biases, the outlook for prognostication is grim. Crit Care 2009; 13:168 13. Elliott D, Davidson JE, Harvey MA, et al: Exploring the scope of post– intensive care syndrome therapy and care: Engagement of non–critical care providers and survivors in a second stakeholders meeting. Crit Care Med 2014; 42:2518–2526 14. Stevens RD, Hart N, Herridge M (Eds): Textbook of Post-ICU Medicine: The Legacy of Critical Care. Oxford, England, Oxford University Press, 2014
Multimodal Monitoring After Traumatic Brain Injury: Useless or Useful?* J. Paul Muizelaar, MD, PhD Department of Neurosurgery Marshall University Huntington, WV
I
t has been almost 40 years ago that intracranial pressure (ICP) monitoring was introduced as a “standard” after severe traumatic brain injury (TBI) (1), and it has been 23 years since we first documented the role of cerebral ischemia (2). Although there are many alleged pathways and factors leading to further, so-called secondary damage after the initial impact, clinical trials designed to interrupt these pathways *See also p. 445. Key Words: cerebral ischemia; multimodal monitoring; severe traumatic brain injury The author has disclosed that he does not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000792
506
www.ccmjournal.org
and so improve outcome after TBI have been unsuccessful. In this respect, it is interesting to note that many “authorities” in TBI feel that the failures of these clinical trials must be directly related to the fact that severe TBI is heterogeneous, pleading for exploration of an array of biomarkers to better classify the different types of TBI in order to design more targeted treatment trials (3). However, when we consider a rather simple and “uniform” type of non-TBI (e.g., embolic stroke), we find that all clinical trials targeting different pathways shown to play a role in ischemic stroke in animal models have failed. The only exception is simple and timely restoration of blood flow to the brain with tissue plasminogen activator clot lysis (4)! Similarly, only averting hypocarbia (via avoidance of hyperventilation that leads to cerebral ischemia) has made a difference in outcome after severe TBI (5, 6). Thus, it currently appears that preventing ischemia or hypoperfusion is the only line of defense with clinical relevance remaining. How do we define ischemia, and how do we monitor for it? In this issue of Critical Care Medicine, it is interesting that in the article by Bouzat et al (7), “hypoperfusion” measured by perfusion CT (PCT) was defined as cerebral blood flow (CBF) February 2015 • Volume 43 • Number 2
Editorials
below 35 mL/100 g/min. This is far above the accepted threshold for infarction of 18 mL/100 g/min in both animals (8) and humans (2). Nevertheless, even with this unusually high threshold, there was a good statistical correlation between hypoperfusion and increased ICP, low brain tissue oxygen tension (Pbto2), and increased lactate/pyruvate ratio (LPR) as measured with hourly cerebral microdialysis samples. Would these correlations have been stronger if a more traditional threshold for hypoperfusion, or even ischemia, were used? As described, the clinician cannot use PCT as an “alarm” for upcoming trouble, as there is too much overlap of findings with or without PCT hypoperfusion (e.g., ICP > 20 mm Hg in 30%, or Pbto2 < 20 mm Hg in 20% with hypoperfusion vs 13% and 9%, respectively, without hypoperfusion) and PCT seems clinically useless. CBF measurements with PCT play an important role in the acute management and decision making in acute ischemic stroke. However, it is unlikely that it will ever play such a role in the acute management of severe TBI. With “spot” measurements with 133Xe or stable xenon CT CBF measurements, we found that frank ischemia occurs mostly in the first 8 hours postinjury and becomes rare after 24 hours (2, 9). This was later confirmed in numerous other studies using a variety of techniques for measuring CBF. The median time of PCT after injury in the study by Bouzat et al (7) was 27 hours. It is a much lower priority in trauma patients who usually need extensive diagnostic studies and resuscitation compared with patients with stroke. On the other hand, we recognize that while a patient’s CBF may be adequate for 23½ hours per day, the half hour in which it is inadequate may cause irreparable damage. Unfortunately, an intermittent monitoring tool such as PCT will never be able to reliably diagnose that critical half hour. Hence, the quest for continuous monitoring techniques for signs of inadequate CBF or oxygen supply to the brain. As various techniques have come and gone, it appears that the “battle” has been decided in favor of continuous Pbto2 monitoring (e.g., Licox), even though it is our impression that is not much used in the United States. The threshold values (10, 15, or 20 mm Hg) for this technique are not firmly established, but the trend and actual values are clear indicators of where we should focus our attention. The LPR can be interpreted as another indicator of ischemia/hypoxia, although disturbed mitochondrial metabolism in the absence of these factors can also produce abnormal values (10). However, we feel that the yield of adding LPR in the accompanying article, albeit statistically significant, is not clinically useful. We have never been supporters of the microdialysis technique for clinical purposes, and this article does
Critical Care Medicine
not change our position on this point, considering the cost, risk, and inconvenience of this technique. Thus, although the yield of even simple ICP monitoring has been questioned recently (11), we feel that the combination of ICP, cerebral perfusion pressure, and Pbto2 monitoring is the most useful and practical. However, monitoring alone is not enough and bold new approaches to correcting hypoperfusion may have to be pursued. We have recently described the successful use of catheter angiography for the diagnosis of vasospasm and its treatment with balloon angioplasty and intra-arterial injection of verapamil after severe head injury (12). This innovative treatment was subsequently endorsed by Faculty of 1000 (13) and so multimodality monitoring has become useful!
REFERENCES
1. Miller JD, Becker DP, Ward JD, et al: Significance of intracranial hypertension in severe head injury. J Neurosurg 1977; 47:503–516 2. Bouma GJ, Muizelaar JP, Choi SC, et al: Cerebral circulation and metabolism after severe traumatic brain injury: The elusive role of ischemia. J Neurosurg 1991; 75:685–693 3. Manley GT, Maas AI: Traumatic brain injury: An international knowledge-based approach. JAMA 2013; 310:473–474 4. del Zoppo GJ, Poeck K, Pessin MS, et al: Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 1992; 32:78–86 5. Muizelaar JP, Marmarou A, Ward JD, et al: Adverse effects of prolonged hyperventilation in patients with severe head injury: A randomized clinical trial. J Neurosurg 1991; 75:731–739 6. Dumont TM, Visioni AJ, Rughani AI, et al: Inappropriate prehospital ventilation in severe traumatic brain injury increases in-hospital mortality. J Neurotrauma 2010; 27:1233–1241 7. Bouzat P, Marques-Vidal P, Zerlauth J-B, et al: Accuracy of Brain Multimodal Monitoring to Detect Cerebral Hypoperfusion After Traumatic Brain Injury. Crit Care Med 2015; 43:445–452 8. Jones TH, Morawetz RB, Crowell RM, et al: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 1981; 54:773–782 9. Bouma GJ, Muizelaar JP, Stringer WA, et al: Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 1992; 77:360–368 10. Verweij BH, Muizelaar JP, Vinas FC, et al: Impaired cerebral mitochondrial function after traumatic brain injury in humans. J Neurosurg 2000; 93:815–820 11. Chesnut RM, Temkin N, Carney N, et al; Global Neurotrauma Research Group: A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012; 367:2471–2481 12. Shahlaie K, Boggan JE, Latchaw RE, et al: Posttraumatic vasospasm detected by continuous brain tissue oxygen monitoring: Treatment with intraarterial verapamil and balloon angioplasty. Neurocrit Care 2009; 10:61–69 13. Marion D: Recommendation of [Shahlaie K, Boggan JE, Latchaw RE, et al, Neurocrit Care 2009; 10:61–69]. F1000Prime Article Recommendations 2008. Available at: http://f1000.com/ prime/1123087. Accessed July 10, 2014
www.ccmjournal.org
507
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
not allow this conclusion. Differences were minimal and the ICU mortality is not a sufficiently robust outcome measure, as influenced as it is by differences in discharge ICU policies and current trend toward earlier ICU discharge. As a more general reflection, we should consider if our insistence on prognostication models based on few variables recorded at an early stage of acute disease is worth the investment they require. In research, analysis of large datasets with multivariable models combining different features is needed to estimate prognosis (10). Yet, variations in outcome cannot be entirely explained even using sophisticated modeling of prognostic variables, which limits application of statistical prediction when decisions are made about early management (11). Probability estimates may help physicians and patients in deciding upon further management, if sufficient time is allocated to gain relevant prognostic information, to evaluate response to treatment (or lack thereof) and to consider patients’ values (12). But perhaps, paraphrasing Taleb (1, 2), “we should concentrate on the consequences of critical illness, which can be known (13, 14), rather than on the probability that they will occur, which can’t.”
REFERENCES
1. Samuel G: The perils of prediction. New York, The Economist, 2007. Available at: http://www.economist.com/node/9253918. Accessed September 28, 2014 2. Taleb NL: The Black Swan: The Impact of the Highly Improbable. Random House, 2007
3. Amos J: L’Aquila Quake: Italy Scientists Guilty of Manslaughter. BBC News, 2012. Available at: http://www.bbc.com/news/worldeurope-20025626. Accessed September 28, 2014 4. Teasdale GM, Nicoll JA, Murray G, et al: Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 1997; 350:1069–1071 5. Adhikari NK, Fowler RA, Bhagwanjee S, et al: Critical care and the global burden of critical illness in adults. Lancet 2010; 376:1339–1346 6. Gostin LO: Legal and ethical responsibilities following brain death: The McMath and Muñoz cases. JAMA 2014; 311:903–904 7. Wijdicks EFM, Kramer AA, Rohs T Jr, et al: Comparison of the Full Outline of UnResponsiveness Score and the Glasgow Coma Scale in Predicting Mortality in Critically Ill Patients. Crit Care Med 2015; 43:439–444 8. Sharshar T, Citerio G, Andrews PJ, et al: Neurological examination of critically ill patients: A pragmatic approach. Report of an ESICM expert panel. Intensive Care Med 2014; 40:484–495 9. Sharshar T, Porcher R, Siami S, et al; Paris-Ouest Study Group on Neurological Effect of Sedation (POSGNES): Brainstem responses can predict death and delirium in sedated patients in intensive care unit. Crit Care Med 2011; 39:1960–1967 10. Teasdale G, Maas A, Lecky F, et al: The Glasgow Coma Scale at 40 years: Standing the test of time. Lancet Neurol 2014; 13:844–854 11. Servadei F: Coma scales. Lancet 2006; 367:548–549 12. Downar J: Even without our biases, the outlook for prognostication is grim. Crit Care 2009; 13:168 13. Elliott D, Davidson JE, Harvey MA, et al: Exploring the scope of post– intensive care syndrome therapy and care: Engagement of non–critical care providers and survivors in a second stakeholders meeting. Crit Care Med 2014; 42:2518–2526 14. Stevens RD, Hart N, Herridge M (Eds): Textbook of Post-ICU Medicine: The Legacy of Critical Care. Oxford, England, Oxford University Press, 2014
Multimodal Monitoring After Traumatic Brain Injury: Useless or Useful?* J. Paul Muizelaar, MD, PhD Department of Neurosurgery Marshall University Huntington, WV
I
t has been almost 40 years ago that intracranial pressure (ICP) monitoring was introduced as a “standard” after severe traumatic brain injury (TBI) (1), and it has been 23 years since we first documented the role of cerebral ischemia (2). Although there are many alleged pathways and factors leading to further, so-called secondary damage after the initial impact, clinical trials designed to interrupt these pathways *See also p. 445. Key Words: cerebral ischemia; multimodal monitoring; severe traumatic brain injury The author has disclosed that he does not have any potential conflicts of interest. Copyright © 2015 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000792
506
www.ccmjournal.org
and so improve outcome after TBI have been unsuccessful. In this respect, it is interesting to note that many “authorities” in TBI feel that the failures of these clinical trials must be directly related to the fact that severe TBI is heterogeneous, pleading for exploration of an array of biomarkers to better classify the different types of TBI in order to design more targeted treatment trials (3). However, when we consider a rather simple and “uniform” type of non-TBI (e.g., embolic stroke), we find that all clinical trials targeting different pathways shown to play a role in ischemic stroke in animal models have failed. The only exception is simple and timely restoration of blood flow to the brain with tissue plasminogen activator clot lysis (4)! Similarly, only averting hypocarbia (via avoidance of hyperventilation that leads to cerebral ischemia) has made a difference in outcome after severe TBI (5, 6). Thus, it currently appears that preventing ischemia or hypoperfusion is the only line of defense with clinical relevance remaining. How do we define ischemia, and how do we monitor for it? In this issue of Critical Care Medicine, it is interesting that in the article by Bouzat et al (7), “hypoperfusion” measured by perfusion CT (PCT) was defined as cerebral blood flow (CBF) February 2015 • Volume 43 • Number 2
Editorials
below 35 mL/100 g/min. This is far above the accepted threshold for infarction of 18 mL/100 g/min in both animals (8) and humans (2). Nevertheless, even with this unusually high threshold, there was a good statistical correlation between hypoperfusion and increased ICP, low brain tissue oxygen tension (Pbto2), and increased lactate/pyruvate ratio (LPR) as measured with hourly cerebral microdialysis samples. Would these correlations have been stronger if a more traditional threshold for hypoperfusion, or even ischemia, were used? As described, the clinician cannot use PCT as an “alarm” for upcoming trouble, as there is too much overlap of findings with or without PCT hypoperfusion (e.g., ICP > 20 mm Hg in 30%, or Pbto2 < 20 mm Hg in 20% with hypoperfusion vs 13% and 9%, respectively, without hypoperfusion) and PCT seems clinically useless. CBF measurements with PCT play an important role in the acute management and decision making in acute ischemic stroke. However, it is unlikely that it will ever play such a role in the acute management of severe TBI. With “spot” measurements with 133Xe or stable xenon CT CBF measurements, we found that frank ischemia occurs mostly in the first 8 hours postinjury and becomes rare after 24 hours (2, 9). This was later confirmed in numerous other studies using a variety of techniques for measuring CBF. The median time of PCT after injury in the study by Bouzat et al (7) was 27 hours. It is a much lower priority in trauma patients who usually need extensive diagnostic studies and resuscitation compared with patients with stroke. On the other hand, we recognize that while a patient’s CBF may be adequate for 23½ hours per day, the half hour in which it is inadequate may cause irreparable damage. Unfortunately, an intermittent monitoring tool such as PCT will never be able to reliably diagnose that critical half hour. Hence, the quest for continuous monitoring techniques for signs of inadequate CBF or oxygen supply to the brain. As various techniques have come and gone, it appears that the “battle” has been decided in favor of continuous Pbto2 monitoring (e.g., Licox), even though it is our impression that is not much used in the United States. The threshold values (10, 15, or 20 mm Hg) for this technique are not firmly established, but the trend and actual values are clear indicators of where we should focus our attention. The LPR can be interpreted as another indicator of ischemia/hypoxia, although disturbed mitochondrial metabolism in the absence of these factors can also produce abnormal values (10). However, we feel that the yield of adding LPR in the accompanying article, albeit statistically significant, is not clinically useful. We have never been supporters of the microdialysis technique for clinical purposes, and this article does
Critical Care Medicine
not change our position on this point, considering the cost, risk, and inconvenience of this technique. Thus, although the yield of even simple ICP monitoring has been questioned recently (11), we feel that the combination of ICP, cerebral perfusion pressure, and Pbto2 monitoring is the most useful and practical. However, monitoring alone is not enough and bold new approaches to correcting hypoperfusion may have to be pursued. We have recently described the successful use of catheter angiography for the diagnosis of vasospasm and its treatment with balloon angioplasty and intra-arterial injection of verapamil after severe head injury (12). This innovative treatment was subsequently endorsed by Faculty of 1000 (13) and so multimodality monitoring has become useful!
REFERENCES
1. Miller JD, Becker DP, Ward JD, et al: Significance of intracranial hypertension in severe head injury. J Neurosurg 1977; 47:503–516 2. Bouma GJ, Muizelaar JP, Choi SC, et al: Cerebral circulation and metabolism after severe traumatic brain injury: The elusive role of ischemia. J Neurosurg 1991; 75:685–693 3. Manley GT, Maas AI: Traumatic brain injury: An international knowledge-based approach. JAMA 2013; 310:473–474 4. del Zoppo GJ, Poeck K, Pessin MS, et al: Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 1992; 32:78–86 5. Muizelaar JP, Marmarou A, Ward JD, et al: Adverse effects of prolonged hyperventilation in patients with severe head injury: A randomized clinical trial. J Neurosurg 1991; 75:731–739 6. Dumont TM, Visioni AJ, Rughani AI, et al: Inappropriate prehospital ventilation in severe traumatic brain injury increases in-hospital mortality. J Neurotrauma 2010; 27:1233–1241 7. Bouzat P, Marques-Vidal P, Zerlauth J-B, et al: Accuracy of Brain Multimodal Monitoring to Detect Cerebral Hypoperfusion After Traumatic Brain Injury. Crit Care Med 2015; 43:445–452 8. Jones TH, Morawetz RB, Crowell RM, et al: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 1981; 54:773–782 9. Bouma GJ, Muizelaar JP, Stringer WA, et al: Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 1992; 77:360–368 10. Verweij BH, Muizelaar JP, Vinas FC, et al: Impaired cerebral mitochondrial function after traumatic brain injury in humans. J Neurosurg 2000; 93:815–820 11. Chesnut RM, Temkin N, Carney N, et al; Global Neurotrauma Research Group: A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med 2012; 367:2471–2481 12. Shahlaie K, Boggan JE, Latchaw RE, et al: Posttraumatic vasospasm detected by continuous brain tissue oxygen monitoring: Treatment with intraarterial verapamil and balloon angioplasty. Neurocrit Care 2009; 10:61–69 13. Marion D: Recommendation of [Shahlaie K, Boggan JE, Latchaw RE, et al, Neurocrit Care 2009; 10:61–69]. F1000Prime Article Recommendations 2008. Available at: http://f1000.com/ prime/1123087. Accessed July 10, 2014
www.ccmjournal.org
507
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
