Editorials
and does not participate to the effects observed in the pres ent study. Unfortunately, the article lacks a sound physiologi cal explanation for the potentially harmful effects of MBL or rather for the protective mechanisms of its deficiency. Some suggestions about potential mechanisms involving a direct action of MBL on cerebral or endothelial cells remain vague. In summary, the presented data give rise to the hope that a specific modulation of neuroinflammation could eventually be a therapeutic approach in neurotrauma, and either the lectin pathway in general or MBL specifically might be a potential target, although the underlying pathophysiological mecha nisms might still remain to be elucidated.
REFERENCES 1. Stead LG, Bodhit AN, Patel PS, et al; Emergency Medicine Traumatic Brain Injury Research Network Investigators: TBI surveillance using the common data elements for traumatic brain injury: A population study. Int J Emerg M ed 2013; 6:5 2. Carney NA, Ghajar J: Guidelines for the management of severe traumatic brain injury. Introduction. J Neurotrauma 2007; 24(Suppl 1 ):S 1-S 2 3. Adams HP Jr, del Zoppo G, Alberts MJ, et al; American Heart Association; American Stroke Association Stroke Council; Clinical Cardiology Council; Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease and Quality of Care O utcom es in Research Interdisciplinary Working G roups: Guidelines for the early management of adults with isch emic stroke: A guideline from the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology
Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care O utcomes in Research Interdisciplinary W orking Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007; 3 8 :1 6 5 5 -1 7 1 1 4. Bratton SL, Chestnut RM, Ghajar J, et al: Guidelines for the manage ment of severe traumatic brain injury. VI. Indications for intracranial pressure monitoring. J Neurotrauma 2007; 24(Suppl 1 ):S 3 7-S 4 4 5. Bratton SL, Chestnut RM, Ghajar J, et al: Guidelines for the manage ment of severe traumatic brain injury. XV. Steroids. J Neurotrauma 2007; 24(Suppl 1 ):S 91-S 95 6. Weinberger JM: Evolving therapeutic approaches to treating acute ischemic stroke. J Neurol S ci 2006; 2 4 9 :1 0 1 -1 0 9 7. Kirkham M, Berg DA, Simon A: Microglia activation during neu roregeneration in the adult vertebrate brain. Neurosci Lett 2011; 4 9 7 :1 1 -1 6 8. Longhi L, Orsini F, De Blasio D, et al: Mannose-Binding Lectin Is Expressed After Clinical and Experimental Traumatic Brain Injury and Its Deletion Is Protective. Crit Care Med 2014; 42:1910-1918 9. Yager PH, You Z, Qin T, et al: Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice. J Cereb B lood Flow Metab 2008; 2 8 :1 0 3 0 -1 0 3 9 10. Cervera A, Planas AM, Justicia C, et al: Genetically-defined deficiency of mannose-binding lectin is associated with protection after experi mental stroke in mice and outcome in human stroke. PLoS One 2010; 5:e8433 11. Trendelenburg M, Theroux P, Stebbins A, et al: Influence of func tional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergo ing primary percutaneous coronary intervention. Eur Heart J 2010; 3 1 :1 1 8 1 -1 1 8 7
Prognostication Following Cardiac Arrest: Do We Have Our Patients’ Safety in Mind?* Romergryko G. Geocadin, MD
Santosh B. Murthy, MD, MPH
Department of Neurology Department of Anesthesiology and Critical Care Medicine Department of Neurosurgery; and Department of Medicine Johns Hopkins University School of Medicine Baltimore, MD
Department of Neurology; and Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore, MD
he practice of prognostication in post cardiac arrest (PCA) patients has grave importance particularly in the era where resources are limited and cost containment is emphasized. Prior to the introduction of therapeutic hypother mia (TH) in comatose survivors of cardiac arrest, a clinical prac tice guideline advocates for 72 hours postarrest as an acceptable time cutoff for prognostication of neurological recovery (1). The introduction of TH shifted the paradigm as it improved out comes and increased attention to the postarrest care. TH has also renewed the interest in prognostication (2). Hence, developing validated prognostic tools and establishing the optimal timing and predictive accuracy of tests used in response to the changes to outcomes that TH has caused is one of the most pressing research needs in postresuscitation care (3).
T
*See also p. 1919. Key Words: cardiac arrest; patient safety; prognostication; therapeutic hypothermia Dr. Geocadin is supported, in part, by 5R 01H L071568 and RO I NS074425. Dr. Geocadin provided expert testimony as Medicolegal Con sult, received grant support from the National Institutes of Health (NIH), and received support for article research from the NIH. Dr. Murthy has disclosed that he does not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/C C M .0000000000000394
C ritical Care Medicine
w w w .c c m jo u rn a l.o rg
1959
Editorials
In this issue of Critical Care Medicine, Golan et al (4) pres ent a meta-analysis on predicting neurological outcome fol lowing TH PCA that included 20 studies with 1,845 patients. Measures of poor neurological outcome were Glasgow outcome score (GOS) of 1-3 or Glasgow-Pittsburgh cerebral perfor mance categories (CPC) score of 3-5. The study assessed sev eral validated tools such as clinical tests, electroencephalogram, somatosensory-evoked potentials (SSEPs), neuroimaging, and serum biomarkers such as neuron-specific enolase and Tau. The authors concluded that bilateral absence of pupillary reflexes more than 24 hours after return of spontaneous circulation was the best predictor of outcomes with a false-positive rate (FPR) of 0.02 (95% Cl, 0.01-0.06), whereas bilateral absence of cor neal reflexes was the second best predictor (FPR of 0.04; 95% Cl, 0.01-0.09). SSEPs accurately prognosticated neurological recovery especially when performed in the first week post arrest (FPR, 0.03; 95% Cl, 0.01-0.07). Notably, the authors cautioned that the specificity of available tests improved when these were performed beyond 72 hours. Moreover, they warned that clini cians should use caution with these predictors as they carry the inherent risk of becoming self-fulfilling. Several meta-analysis on this topic have been published (5,6), but some of the strengths of the study by Golan et al (4) include the comprehensive inclusion of relevant observational, retrospective, and prospective studies, along with formal appraisal of the quality of evidence. One of the highlights of this study is the standardized approach with regard to timing of the tests. By contrast, the meta-analysis by Sandroni et al (5) examined the role of different tests at different time points, making its application in clinical practice less feasible. Fur therm ore, Golan et al (4) included predictors of neurological outcome within the first 14 days, as opposed to 7 days by San droni et al (5), to minimize the confounding effect of sedation and paralytics. Another meta-analysis by Kamps et al (6) that included 10 studies also reported similar findings regarding the diagnostic accuracy o f pupillary reflexes and somatosen sory potentials when perform ed within 72 hours. Despite the similarities in the sensitivity analyses, the study by Golan et al (4) had narrower CIs due to the inclusion of more studies and correspondingly a larger sample size. As we compare the three meta-analyses, all three studies provide some serious caution regarding their observations and recommendations. Critical evaluation of published literature on neuroprognos tication raises a few noteworthy questions. First, on timing, are we justified in using the 72-hour cutoff for arriving at a prog nosis in patients treated with TH? A recent study of 194 patients reported that the time to awakening after PCA was variable and often longer than 72 hours (7). As Golan et al (4) cautioned us that the specificity of test increased beyond 72 hours, and with early prognostication of poor outcome at 72 hours resulting in withdrawal of life-sustaining therapies and death, what is the patient safety implication of this practice? Second, on study design, the lack of blinding in the vast majority of the prognos tication studies supports the idea that self-fulfilling prophecy is comm on in this area. How many patients are actually harmed by self-fulfilling prophecy? It is rather intriguing to find that 1960
w w w .c c m jo u r n a l.o r g
blinding, which is considered quintessential in randomized clinical trials on drugs and interventions, is not the norm in prognostication studies. Self-fulfilling prophecy can have a sig nificant negative impact on our ability to fully appreciate the effects of treatments and interventions (8), and withdrawal of life-sustaining therapies has a profound confounding effect on the predictive value of the tests and overall PCA mortality (9, 10). Third, earmarking the 3- or 6-m onth follow-up as standard for long-term outcomes particularly in the context of recent evidence suggesting a more prolonged recovery following PCA (11). Fourth, are the measures of outcome currently in vogue, such as CPC or GOS, truly the best surrogates of neurological recovery in these patients? Studies have shown CPC to correlate poorly with quality of life, whereas GOS is an inadequate mea sure of cognitive outcomes (12-15). Despite these limitations, we commend Golan et al (4) on per forming this meta-analysis on a very important yet complex topic. As this study tries to show that simple bedside clinical tests and somatosensory potentials have a high neuroprognostic predictive ability, mostly when performed after 72 hours following cardiac arrest, we need to ponder on our motivations for prognostication. A few years before the introduction of TH, the Institutes of Medi cine published the report on a comprehensive strategy by which government, healthcare providers, industry, and consumers can reduce preventable medical errors (16). This report brought heightened awareness on patient safety as a paradigm shifter that affected the practice of medicine in general and critical care medi cine in particular. As we juxtapose the two paradigm shifters of TH and patient safety in the practice of early prognostication, is there anything we can do to keep these patients safer? How many patients are potentially affected by early prognostication? Con sidering that there are over 400,000 cardiac arrests in the United States per year (15), and while the mortality seems to be trending downward (17, 18), majority of PCA survivors are comatose for variable periods of time initially, and hence susceptible to early prognostication, which may result in withdrawal of life-sustaining therapies. As we try to address the limitations of existing prognos tication practices by designing studies with better study design, newer and better prognostic tests, and more comprehensive bat tery of functional and neurocognitive outcome measures, are we subjecting our patients to unsafe early prognostication practices in our pursuit to possibly minimize suffering and conserve valu able resources? With all the limitations and cautions related to early prognostication, the time has come that we approach prog nostication with our patients’ safety in mind.
REFERENCES 1. W ijdicks EF, Hijdra A, Young GB, et al; Quality Standards Subcommittee of the American Academy of Neurology: Practice parameter: Prediction of outcome in comatose survivors after car diopulmonary resuscitation (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 6 7 :2 0 3 -2 1 0 2. Lucas JM, Cocchi MN, Salciccioli J, e ta l: Neurologic recovery after therapeutic hypothermia in patients with post-cardiac arrest myoclo nus. Resuscitation 2012; 8 3 :2 6 5 -2 6 9 3. Young G B: Clinical practice. Neurologic prognosis after cardiac arrest. N Engl J Med 2009; 3 6 1 :6 0 5 -6 1 1
August 2014 • Volume 42 • Number 8
Editorials 4. Golan E, Barrett K, Alali AS, et al: Predicting Neurologic Outcome After Targeted Temperature Management for Cardiac Arrest: Systematic Review and Meta-Analysis. Crit Care Med 2014; 42:1919-1930 5. Sandroni C, Cavallaro F, Callaway CW, et al: Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: A systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation 2013; 84 :1 3 2 4 -1 3 3 8 6. Kamps MJ, Horn J, Oddo M, et al: Prognostication of neurologic out come in cardiac arrest patients after mild therapeutic hypothermia: A meta-analysis of the current literature. Intensive Care Med 2013; 39:1671-1682 7. Grossestreuer AV, Abella BS, Leary M, et al: Time to awakening and neurologic outcome in therapeutic hypothermia-treated cardiac arrest patients. Resuscitation 2013; 84:1741 -1746 8. Geocadin RG, Peberdy MA, Lazar RM: Poor survival after cardiac arrest resuscitation: A self-fulfilling prophecy or biologic destiny? Crit Care Med 2012; 40:979-980 9. Tsai MS, Chen JY, Chen WJ, et al: Do we need to wait longer for car diac arrest survivor to wake up in hypothermia era? Am J Emerg Med 2013; 31:888.e5-888.e6 10. Gold B, Puertas L, Davis SP, et al: Awakening after cardiac arrest and post resuscitation hypothermia: Are we pulling the plug too early? Resuscitation 2014; 85:211-214
11. Chan PS, Nallamothu BK, Krumholz HM, et al; American Heart Association Get with the Guidelines-Resuscitation Investigators: Long-term outcomes in elderly survivors of in-hospital cardiac arrest. N Engl J Med 2013; 368:1019-1026 12. Rittenberger JC, Raina K, Holm MB, et al: Association between Cerebral Performance Category, Modified Rankin Scale, and discharge disposition after cardiac arrest. Resuscitation 2011; 82:1036-1040 13. Raina KD, Callaway C, Rittenberger JC, etal: Neurological and functional status following cardiac arrest: Method and tool utility. Resuscitation 2008; 79:249-256 14. Stiell IG, Nesbitt LP, Nichol G, etal; OPALS Study Group: Comparison of the Cerebral Performance Category score and the Health Utilities Index for survivors of cardiac arrest. Ann Emerg Med 2009;53:241-248 15. Elliott VJ, Rodgers DL, Brett SJ: Systematic review of quality of life and other patient-centred outcomes after cardiac arrest survival. Resuscitation 2011; 82:247-256 16. National Research Council: To Err Is Human: Building a Safer Health System. Washington, DC, The National Academies Press, 2000 17. Fugate JE, Brinjikji W, Mandrekar JN, et al: Post-cardiac arrest mortal ity is declining: A study of the US National Inpatient Sample 2001 to 2009. Circulation 2012; 126:546-550 18. Girotra S, Chan PS: Trends in survival after in-hospital cardiac arrest. N Engl J Med 2013; 368:680-681
Angiotensin-ll: More Than Just Another Vasoconstrictor to Treat Septic Shock-Induced Hypotension?* Pierre Asfar, MD, PhD
Nicolas Lerolle, MD, PhD
Departement de Reanimation Medicale et de Medecine Hyperbare Centre Hospitalier Universitaire Angers, France
Departement de Reanimation Medicale et de Medecine Hyperbare Centre Hospitalier Universitaire Angers, France
Lakhmir Chawla, MD
Peter Radermacher, MD, PhD
Department of Anesthesiology and Critical Care Medicine The George Washington University Washington, DC
Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung Klinik fur Anasthesiologie Universitatsklinikum Ulm, Germany
*See also p. e550. Key Words: enalapril; gluconeogenesis; kidney blood flow; mitochondrial respiratory chain; norepinephrine Dr. Asfar consulted for and lectured for Laboratoire de Fractionnement et de Biotechnologie, France. His institution received grant support (Dr. Asfar is the principal investigator of two academic randomized controlled trials funded by the French Ministry of Health). Dr. Chawla disclosed that George Washington University has filed an international patent on the use of angiotensin-ll for the treatment of shock. The remaining authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000436
Critical Care Medicine
eptic shock is defined as sepsis-induced hypotension per sisting despite adequate fluid resuscitation, and conse quently vasopressors are needed to “maintain adequate blood pressure (1).” Norepinephrine is currently recom mended as the first-choice vasopressor; epinephrine and vaso pressin “can be added when an additional agent is needed” and/or “with the intent of either raising mean arterial pres sure or decreasing norepinephrine dosage (1).” So far, despite the demonstration of beneficial effects in subgroup analyses, adding vasopressin to norepinephrine did not improve overall
S
w w w .c c m jo u rn a l.o rg
1961
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.
and does not participate to the effects observed in the pres ent study. Unfortunately, the article lacks a sound physiologi cal explanation for the potentially harmful effects of MBL or rather for the protective mechanisms of its deficiency. Some suggestions about potential mechanisms involving a direct action of MBL on cerebral or endothelial cells remain vague. In summary, the presented data give rise to the hope that a specific modulation of neuroinflammation could eventually be a therapeutic approach in neurotrauma, and either the lectin pathway in general or MBL specifically might be a potential target, although the underlying pathophysiological mecha nisms might still remain to be elucidated.
REFERENCES 1. Stead LG, Bodhit AN, Patel PS, et al; Emergency Medicine Traumatic Brain Injury Research Network Investigators: TBI surveillance using the common data elements for traumatic brain injury: A population study. Int J Emerg M ed 2013; 6:5 2. Carney NA, Ghajar J: Guidelines for the management of severe traumatic brain injury. Introduction. J Neurotrauma 2007; 24(Suppl 1 ):S 1-S 2 3. Adams HP Jr, del Zoppo G, Alberts MJ, et al; American Heart Association; American Stroke Association Stroke Council; Clinical Cardiology Council; Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease and Quality of Care O utcom es in Research Interdisciplinary Working G roups: Guidelines for the early management of adults with isch emic stroke: A guideline from the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology
Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care O utcomes in Research Interdisciplinary W orking Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007; 3 8 :1 6 5 5 -1 7 1 1 4. Bratton SL, Chestnut RM, Ghajar J, et al: Guidelines for the manage ment of severe traumatic brain injury. VI. Indications for intracranial pressure monitoring. J Neurotrauma 2007; 24(Suppl 1 ):S 3 7-S 4 4 5. Bratton SL, Chestnut RM, Ghajar J, et al: Guidelines for the manage ment of severe traumatic brain injury. XV. Steroids. J Neurotrauma 2007; 24(Suppl 1 ):S 91-S 95 6. Weinberger JM: Evolving therapeutic approaches to treating acute ischemic stroke. J Neurol S ci 2006; 2 4 9 :1 0 1 -1 0 9 7. Kirkham M, Berg DA, Simon A: Microglia activation during neu roregeneration in the adult vertebrate brain. Neurosci Lett 2011; 4 9 7 :1 1 -1 6 8. Longhi L, Orsini F, De Blasio D, et al: Mannose-Binding Lectin Is Expressed After Clinical and Experimental Traumatic Brain Injury and Its Deletion Is Protective. Crit Care Med 2014; 42:1910-1918 9. Yager PH, You Z, Qin T, et al: Mannose binding lectin gene deficiency increases susceptibility to traumatic brain injury in mice. J Cereb B lood Flow Metab 2008; 2 8 :1 0 3 0 -1 0 3 9 10. Cervera A, Planas AM, Justicia C, et al: Genetically-defined deficiency of mannose-binding lectin is associated with protection after experi mental stroke in mice and outcome in human stroke. PLoS One 2010; 5:e8433 11. Trendelenburg M, Theroux P, Stebbins A, et al: Influence of func tional deficiency of complement mannose-binding lectin on outcome of patients with acute ST-elevation myocardial infarction undergo ing primary percutaneous coronary intervention. Eur Heart J 2010; 3 1 :1 1 8 1 -1 1 8 7
Prognostication Following Cardiac Arrest: Do We Have Our Patients’ Safety in Mind?* Romergryko G. Geocadin, MD
Santosh B. Murthy, MD, MPH
Department of Neurology Department of Anesthesiology and Critical Care Medicine Department of Neurosurgery; and Department of Medicine Johns Hopkins University School of Medicine Baltimore, MD
Department of Neurology; and Department of Anesthesiology and Critical Care Medicine Johns Hopkins University School of Medicine Baltimore, MD
he practice of prognostication in post cardiac arrest (PCA) patients has grave importance particularly in the era where resources are limited and cost containment is emphasized. Prior to the introduction of therapeutic hypother mia (TH) in comatose survivors of cardiac arrest, a clinical prac tice guideline advocates for 72 hours postarrest as an acceptable time cutoff for prognostication of neurological recovery (1). The introduction of TH shifted the paradigm as it improved out comes and increased attention to the postarrest care. TH has also renewed the interest in prognostication (2). Hence, developing validated prognostic tools and establishing the optimal timing and predictive accuracy of tests used in response to the changes to outcomes that TH has caused is one of the most pressing research needs in postresuscitation care (3).
T
*See also p. 1919. Key Words: cardiac arrest; patient safety; prognostication; therapeutic hypothermia Dr. Geocadin is supported, in part, by 5R 01H L071568 and RO I NS074425. Dr. Geocadin provided expert testimony as Medicolegal Con sult, received grant support from the National Institutes of Health (NIH), and received support for article research from the NIH. Dr. Murthy has disclosed that he does not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/C C M .0000000000000394
C ritical Care Medicine
w w w .c c m jo u rn a l.o rg
1959
Editorials
In this issue of Critical Care Medicine, Golan et al (4) pres ent a meta-analysis on predicting neurological outcome fol lowing TH PCA that included 20 studies with 1,845 patients. Measures of poor neurological outcome were Glasgow outcome score (GOS) of 1-3 or Glasgow-Pittsburgh cerebral perfor mance categories (CPC) score of 3-5. The study assessed sev eral validated tools such as clinical tests, electroencephalogram, somatosensory-evoked potentials (SSEPs), neuroimaging, and serum biomarkers such as neuron-specific enolase and Tau. The authors concluded that bilateral absence of pupillary reflexes more than 24 hours after return of spontaneous circulation was the best predictor of outcomes with a false-positive rate (FPR) of 0.02 (95% Cl, 0.01-0.06), whereas bilateral absence of cor neal reflexes was the second best predictor (FPR of 0.04; 95% Cl, 0.01-0.09). SSEPs accurately prognosticated neurological recovery especially when performed in the first week post arrest (FPR, 0.03; 95% Cl, 0.01-0.07). Notably, the authors cautioned that the specificity of available tests improved when these were performed beyond 72 hours. Moreover, they warned that clini cians should use caution with these predictors as they carry the inherent risk of becoming self-fulfilling. Several meta-analysis on this topic have been published (5,6), but some of the strengths of the study by Golan et al (4) include the comprehensive inclusion of relevant observational, retrospective, and prospective studies, along with formal appraisal of the quality of evidence. One of the highlights of this study is the standardized approach with regard to timing of the tests. By contrast, the meta-analysis by Sandroni et al (5) examined the role of different tests at different time points, making its application in clinical practice less feasible. Fur therm ore, Golan et al (4) included predictors of neurological outcome within the first 14 days, as opposed to 7 days by San droni et al (5), to minimize the confounding effect of sedation and paralytics. Another meta-analysis by Kamps et al (6) that included 10 studies also reported similar findings regarding the diagnostic accuracy o f pupillary reflexes and somatosen sory potentials when perform ed within 72 hours. Despite the similarities in the sensitivity analyses, the study by Golan et al (4) had narrower CIs due to the inclusion of more studies and correspondingly a larger sample size. As we compare the three meta-analyses, all three studies provide some serious caution regarding their observations and recommendations. Critical evaluation of published literature on neuroprognos tication raises a few noteworthy questions. First, on timing, are we justified in using the 72-hour cutoff for arriving at a prog nosis in patients treated with TH? A recent study of 194 patients reported that the time to awakening after PCA was variable and often longer than 72 hours (7). As Golan et al (4) cautioned us that the specificity of test increased beyond 72 hours, and with early prognostication of poor outcome at 72 hours resulting in withdrawal of life-sustaining therapies and death, what is the patient safety implication of this practice? Second, on study design, the lack of blinding in the vast majority of the prognos tication studies supports the idea that self-fulfilling prophecy is comm on in this area. How many patients are actually harmed by self-fulfilling prophecy? It is rather intriguing to find that 1960
w w w .c c m jo u r n a l.o r g
blinding, which is considered quintessential in randomized clinical trials on drugs and interventions, is not the norm in prognostication studies. Self-fulfilling prophecy can have a sig nificant negative impact on our ability to fully appreciate the effects of treatments and interventions (8), and withdrawal of life-sustaining therapies has a profound confounding effect on the predictive value of the tests and overall PCA mortality (9, 10). Third, earmarking the 3- or 6-m onth follow-up as standard for long-term outcomes particularly in the context of recent evidence suggesting a more prolonged recovery following PCA (11). Fourth, are the measures of outcome currently in vogue, such as CPC or GOS, truly the best surrogates of neurological recovery in these patients? Studies have shown CPC to correlate poorly with quality of life, whereas GOS is an inadequate mea sure of cognitive outcomes (12-15). Despite these limitations, we commend Golan et al (4) on per forming this meta-analysis on a very important yet complex topic. As this study tries to show that simple bedside clinical tests and somatosensory potentials have a high neuroprognostic predictive ability, mostly when performed after 72 hours following cardiac arrest, we need to ponder on our motivations for prognostication. A few years before the introduction of TH, the Institutes of Medi cine published the report on a comprehensive strategy by which government, healthcare providers, industry, and consumers can reduce preventable medical errors (16). This report brought heightened awareness on patient safety as a paradigm shifter that affected the practice of medicine in general and critical care medi cine in particular. As we juxtapose the two paradigm shifters of TH and patient safety in the practice of early prognostication, is there anything we can do to keep these patients safer? How many patients are potentially affected by early prognostication? Con sidering that there are over 400,000 cardiac arrests in the United States per year (15), and while the mortality seems to be trending downward (17, 18), majority of PCA survivors are comatose for variable periods of time initially, and hence susceptible to early prognostication, which may result in withdrawal of life-sustaining therapies. As we try to address the limitations of existing prognos tication practices by designing studies with better study design, newer and better prognostic tests, and more comprehensive bat tery of functional and neurocognitive outcome measures, are we subjecting our patients to unsafe early prognostication practices in our pursuit to possibly minimize suffering and conserve valu able resources? With all the limitations and cautions related to early prognostication, the time has come that we approach prog nostication with our patients’ safety in mind.
REFERENCES 1. W ijdicks EF, Hijdra A, Young GB, et al; Quality Standards Subcommittee of the American Academy of Neurology: Practice parameter: Prediction of outcome in comatose survivors after car diopulmonary resuscitation (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2006; 6 7 :2 0 3 -2 1 0 2. Lucas JM, Cocchi MN, Salciccioli J, e ta l: Neurologic recovery after therapeutic hypothermia in patients with post-cardiac arrest myoclo nus. Resuscitation 2012; 8 3 :2 6 5 -2 6 9 3. Young G B: Clinical practice. Neurologic prognosis after cardiac arrest. N Engl J Med 2009; 3 6 1 :6 0 5 -6 1 1
August 2014 • Volume 42 • Number 8
Editorials 4. Golan E, Barrett K, Alali AS, et al: Predicting Neurologic Outcome After Targeted Temperature Management for Cardiac Arrest: Systematic Review and Meta-Analysis. Crit Care Med 2014; 42:1919-1930 5. Sandroni C, Cavallaro F, Callaway CW, et al: Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: A systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. Resuscitation 2013; 84 :1 3 2 4 -1 3 3 8 6. Kamps MJ, Horn J, Oddo M, et al: Prognostication of neurologic out come in cardiac arrest patients after mild therapeutic hypothermia: A meta-analysis of the current literature. Intensive Care Med 2013; 39:1671-1682 7. Grossestreuer AV, Abella BS, Leary M, et al: Time to awakening and neurologic outcome in therapeutic hypothermia-treated cardiac arrest patients. Resuscitation 2013; 84:1741 -1746 8. Geocadin RG, Peberdy MA, Lazar RM: Poor survival after cardiac arrest resuscitation: A self-fulfilling prophecy or biologic destiny? Crit Care Med 2012; 40:979-980 9. Tsai MS, Chen JY, Chen WJ, et al: Do we need to wait longer for car diac arrest survivor to wake up in hypothermia era? Am J Emerg Med 2013; 31:888.e5-888.e6 10. Gold B, Puertas L, Davis SP, et al: Awakening after cardiac arrest and post resuscitation hypothermia: Are we pulling the plug too early? Resuscitation 2014; 85:211-214
11. Chan PS, Nallamothu BK, Krumholz HM, et al; American Heart Association Get with the Guidelines-Resuscitation Investigators: Long-term outcomes in elderly survivors of in-hospital cardiac arrest. N Engl J Med 2013; 368:1019-1026 12. Rittenberger JC, Raina K, Holm MB, et al: Association between Cerebral Performance Category, Modified Rankin Scale, and discharge disposition after cardiac arrest. Resuscitation 2011; 82:1036-1040 13. Raina KD, Callaway C, Rittenberger JC, etal: Neurological and functional status following cardiac arrest: Method and tool utility. Resuscitation 2008; 79:249-256 14. Stiell IG, Nesbitt LP, Nichol G, etal; OPALS Study Group: Comparison of the Cerebral Performance Category score and the Health Utilities Index for survivors of cardiac arrest. Ann Emerg Med 2009;53:241-248 15. Elliott VJ, Rodgers DL, Brett SJ: Systematic review of quality of life and other patient-centred outcomes after cardiac arrest survival. Resuscitation 2011; 82:247-256 16. National Research Council: To Err Is Human: Building a Safer Health System. Washington, DC, The National Academies Press, 2000 17. Fugate JE, Brinjikji W, Mandrekar JN, et al: Post-cardiac arrest mortal ity is declining: A study of the US National Inpatient Sample 2001 to 2009. Circulation 2012; 126:546-550 18. Girotra S, Chan PS: Trends in survival after in-hospital cardiac arrest. N Engl J Med 2013; 368:680-681
Angiotensin-ll: More Than Just Another Vasoconstrictor to Treat Septic Shock-Induced Hypotension?* Pierre Asfar, MD, PhD
Nicolas Lerolle, MD, PhD
Departement de Reanimation Medicale et de Medecine Hyperbare Centre Hospitalier Universitaire Angers, France
Departement de Reanimation Medicale et de Medecine Hyperbare Centre Hospitalier Universitaire Angers, France
Lakhmir Chawla, MD
Peter Radermacher, MD, PhD
Department of Anesthesiology and Critical Care Medicine The George Washington University Washington, DC
Sektion Anasthesiologische Pathophysiologie und Verfahrensentwicklung Klinik fur Anasthesiologie Universitatsklinikum Ulm, Germany
*See also p. e550. Key Words: enalapril; gluconeogenesis; kidney blood flow; mitochondrial respiratory chain; norepinephrine Dr. Asfar consulted for and lectured for Laboratoire de Fractionnement et de Biotechnologie, France. His institution received grant support (Dr. Asfar is the principal investigator of two academic randomized controlled trials funded by the French Ministry of Health). Dr. Chawla disclosed that George Washington University has filed an international patent on the use of angiotensin-ll for the treatment of shock. The remaining authors have disclosed that they do not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000436
Critical Care Medicine
eptic shock is defined as sepsis-induced hypotension per sisting despite adequate fluid resuscitation, and conse quently vasopressors are needed to “maintain adequate blood pressure (1).” Norepinephrine is currently recom mended as the first-choice vasopressor; epinephrine and vaso pressin “can be added when an additional agent is needed” and/or “with the intent of either raising mean arterial pres sure or decreasing norepinephrine dosage (1).” So far, despite the demonstration of beneficial effects in subgroup analyses, adding vasopressin to norepinephrine did not improve overall
S
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1961
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