Must One Be a Global End-Diastolic Index Master to Treat Subarachnoid Hemorrhage?* Patrick Mailloux, DO Division of Pulmonary and Critical Care Medicine Baystate Medical Center Springfield, MA • lor patients suffering from aneurysmal subarachnoid 3-~| hemorrhage (SAH), the "dark side" is the risk of ongo-¿^ ing complications, such as delayed cerebral ischemia (DCI) firom vasospasm. SAH leads to challenges in maintaining normal blood volume and patients with hypovolemia are at increased risk for DCI (1, 2). Fflbrts to augment cerebral perfusion and avoid DCI include hypervolemia, hemodilution, and hypertension, the so-called triple-H therapy. The first description of this practice took place in 1976 with the publication of a case series showing alleviation of ischémie symptoms via the expansion of blood volume and vasopressor augmented blood pressure (3). In 1982, Kassell et al (1) demonstrated a strategy to increase intravascular blood volume and block vagal depressor response in combination with the administration of antidiuretics and vasopressor agents reversed neurological deterioration in a large proportion of patients with angiographically confirmed vasospasm. This came at the cost of causing pulmonary edema, dilutional hyponatremia, rebleeding, coagulopathy, and myocardial infarction (1). Despite the associated risks, triple-H therapy became the mainstay of therapy for SAH patients with secured aneurysms. Two randomized, controlled studies (4, 5) attempted to prove postoperative, prophylactic hyperdynamic, hypervolemic (HV) therapy beneficial in SAH patients. Lennihan et al (4) randomly assigned patients to receive either HV or normovolemic therapy. The HV patients received more fluid and had higher pulmonary artery diastolic and central venous pressures (CVPs), but this did not translate to any efl^ect on total fluid balance or blood volume. Curiously, the investigators did not account for the impact on cardiac output, and neither cerebral blood flow nor the prevalence of symptomatic vasospasm was different between the groups (4). Egge et al (5) successfully induced hypervolemia, hypertension, and hemodilution but had no impact with respect to the prevalence of cerebral vasospasm, cerebral blood flow, or 1-year clinical follow-up assessments. In this trial, more complications occurred in the intervention group accompanied by higher costs (5).
*Seealso p. 1348. Key Words: delayed cerebral ischemia; euvolemia; global end-diastolic index; triple-h therapy; vasospasm The author 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/CCM.0000000000000244
Critical Care Medicine
Published guidelines (6, 7) and reviews (8) no longer endorse the use of prophylactic or therapeutic hypervolemia for treating SAH patients. Rather, the recommendations are to target euvolemia with augmentation of blood pressure as dictated by the clinical circumstances. This concept is supported by evidence showing the hypertension component of triple-H therapy is responsible for increasing cerebral blood flow and oxygénation (9, 10). Serious questions remain in terms of the optimal method to assess volume status and ensure a state of euvolemia. Hoff et al (11) showed no association between circulating blood volume and either daily or cumulative fluid balance in SAH patients, eliminating these often used variables as reliable to ensure neutral fluid balance. Furthermore, the commonly used static measures of CVP and pulmonary artery occlusion pressure (PAOP) show no correlation with blood volume or fluid responsiveness and should not be used to manage fluid balance goals (12,13). So where does that leave the clinician trying to stay on the light side of volume management and treating SAH patients? In this issue of Critical Care Medicine, Tagami et al ( 14) look at the relationship of global end-diastolic index (GEDI, normal range 680-800 mL/m'') to the development of DCI and pulmonary edema in patients with SAH. CEDÍ is thefillingvolume of all four heart chambers indexed to body surface area. It serves as a measure of preload and is known to be a more accurate measurement of preload than CVP or PAOP (12, 15). In this prospective, multicenter, noninterventional trial, the authors studied correlations between CEDI and the occurrence of DCI and pulmonary edema. They measured cardiac function in eligible patients with pulse contour analysis, including cardiac output, CEDI, extravascular lung water, global ejection fraction, and systemic vascular resistance. The primary endpoints were the occurrence of DCI, defined as symptomatic vasospasm, infarction related to vasospasm, or both; and severe pulmonary edema, defined as an extravascular lung water index (ELWI) more than 14mL/kg within 14 days of SAH. Even though there was no significant difference in net fluid balance between DCI and non-DCI groups during the 14-day study period, the authors found patients developing DCI had a lower GEDI during the first two phases (phase 1, days 1-3; phase 2, days 4-7) following hemorrhage. The GEDI threshold best correlating with the development of DCI was 822mL/m^ (73% sensitivity, 64% specificity) with an area under the receiver operating characteristic (ROC) curve of 0.66 (95% CI, 0.56-0.76). Related to pulmonary edema, the phase 2 GEDI was an important variable relative to the occurrence of pulmonary edema. A GEDI threshold of 921 mL/m*^ (72% sensitivity, 71% specificity) produced an ROC with an area under the curve of 0.77 (95% CI, 0.69-0.85). There was no significant difference in cumulative fluid balance between the pulmonary edema and nonpulmonary edema groups. www.ccmjournal.org
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Editorials
Even though GEDI correlates with DCI and pulmonary edema in SAH patients, it is not yet ready to assume the role of the guardian for at-risk SAH patients as there are limitations to this study. This was an observational analysis with patients passively monitored once daily to obtain CEDI and ELWI measurements. Critical care clinicians recognize SAH patients are quite dynamic and assessing hemodynamic variables with limited frequency is fraught with peril. The absence or presence of pulmonary edema relied solely on ELWI and was not correlated with other subjective findings, such as hypoxemia, chest radiographs, or the need to institute diuresis. The SAH severity did not statistically correlate with occurrence of DCI which is contrary to estabhshed findings and weakens the ability to draw cause and effect conclusions. The area under the ROC for GEDI associated with DCI is only 0.66, suggesting one variable alone is not enough to fully explain the occurrence of DCI in at-risk patients, and there are likely many other factors influencing the outcomes once you adjust for GEDI. This study provides important fodder for further development of interventional trials to manage patients with aneurysmal SAH. It is clear targeting euvolemia is an important goal and developing standards based on dynamic cardiac variables rather than archaic static pressure measurements may allow those caring for the neurocritically ill to avoid the dark side of SAH. Perhaps, clinicians will evolve into GEDI masters while seeking the correct forces to avoid DCI.
REFERENCES 1. Kassell NF, Peerless SJ, Dunward QJ, et al: Treatment of ischémie deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery 1982; 11:337-343 2. Solomon RA, Post KD, McMurtry JG: Depression of circulating blood volume in patients after subarachnoid hemorrhage: Implications for the management of symptomatic vasospasm. Neurosurgery 1984; 15:354-361 3. Kosnik EJ, Hunt WE: Postoperative hypertension in the management of patients with intracraniai arterial aneurysms. J Neurosurg 1976; 45:148-154
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4. Lennihan L, Mayer SA, Fink ME, et al: Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage. Stroke 2000; 31:383-391 5. Egge A, Waterloo K, Sjaholm H, et al: Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: A clinical, prospective, randomized, controlled study. Neurosurgery 2001; 49:593-605 6. Diringer MN, BleckTP, Claude Hemphill J 3rd, et al; Neurocritical Care Society: Critical care management of patients following aneurysmal subarachnoid hemorrhage: Recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neuroerit Care 2011; 15:211-240 7. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology: Guidelines for the management of aneurysmal subarachnoid hemorrhage: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2012; 43:1711-1737 8. Rinkel GJE, Feigin VL, Algra A, et al: Circulatory volume expansion therapy for aneurysmal subarachnoid hemorrhage (review). Cochrane Database Syst Rev 2004; CD000483 9. Muench E, Horn P, Bauhuf C, et al: Effects of hypervolemia and hypertension on regional cerebral blood flow, intracraniai pressure, and brain tissue oxygénation after subarachnoid hemorrhage. Crit Care Med 2007; 35:1 844-1 851 ; quiz 1852 10. Dankbaar JW, Slooter AJ, Rinkel GJ, et al: Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid hemorrhage: A systematic review. Crit Care 2010; 14:R23 11. Hoft RG, van Dijk GW, Algra A, et al: Fluid balance and blood volume measurement after aneurysmal subarachnoid hemorrhage. Neuroerit Care 2008; 8:391-397 1 2. Marik PE, Baram M, Vahid B: Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008; 134:172-178 13. Osman D, Ridel C, Ray P, et al: Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med 2007; 35:64-68 14. Tagami T, Kuwamoto K, Watanabe A, et al; SAH PiCCC Study Group: Optimal Range of Global End-Diastolic Volume for Fluid Management After Aneurysmal Subarachnoid Hemorrhage: A Multicenter Prospective Cohort Study. Crit Care Med 2014; 42:1348-1356 15. Michard F, Alaya S, Zarka V et al: Global end-diastolic volume as an indicator of cardiac preload in patients with septic shock. Chest 2003; 124:1900-1908
June 2014 • Volume 42 • Number 6
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.
*Seealso p. 1348. Key Words: delayed cerebral ischemia; euvolemia; global end-diastolic index; triple-h therapy; vasospasm The author 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/CCM.0000000000000244
Critical Care Medicine
Published guidelines (6, 7) and reviews (8) no longer endorse the use of prophylactic or therapeutic hypervolemia for treating SAH patients. Rather, the recommendations are to target euvolemia with augmentation of blood pressure as dictated by the clinical circumstances. This concept is supported by evidence showing the hypertension component of triple-H therapy is responsible for increasing cerebral blood flow and oxygénation (9, 10). Serious questions remain in terms of the optimal method to assess volume status and ensure a state of euvolemia. Hoff et al (11) showed no association between circulating blood volume and either daily or cumulative fluid balance in SAH patients, eliminating these often used variables as reliable to ensure neutral fluid balance. Furthermore, the commonly used static measures of CVP and pulmonary artery occlusion pressure (PAOP) show no correlation with blood volume or fluid responsiveness and should not be used to manage fluid balance goals (12,13). So where does that leave the clinician trying to stay on the light side of volume management and treating SAH patients? In this issue of Critical Care Medicine, Tagami et al ( 14) look at the relationship of global end-diastolic index (GEDI, normal range 680-800 mL/m'') to the development of DCI and pulmonary edema in patients with SAH. CEDÍ is thefillingvolume of all four heart chambers indexed to body surface area. It serves as a measure of preload and is known to be a more accurate measurement of preload than CVP or PAOP (12, 15). In this prospective, multicenter, noninterventional trial, the authors studied correlations between CEDI and the occurrence of DCI and pulmonary edema. They measured cardiac function in eligible patients with pulse contour analysis, including cardiac output, CEDI, extravascular lung water, global ejection fraction, and systemic vascular resistance. The primary endpoints were the occurrence of DCI, defined as symptomatic vasospasm, infarction related to vasospasm, or both; and severe pulmonary edema, defined as an extravascular lung water index (ELWI) more than 14mL/kg within 14 days of SAH. Even though there was no significant difference in net fluid balance between DCI and non-DCI groups during the 14-day study period, the authors found patients developing DCI had a lower GEDI during the first two phases (phase 1, days 1-3; phase 2, days 4-7) following hemorrhage. The GEDI threshold best correlating with the development of DCI was 822mL/m^ (73% sensitivity, 64% specificity) with an area under the receiver operating characteristic (ROC) curve of 0.66 (95% CI, 0.56-0.76). Related to pulmonary edema, the phase 2 GEDI was an important variable relative to the occurrence of pulmonary edema. A GEDI threshold of 921 mL/m*^ (72% sensitivity, 71% specificity) produced an ROC with an area under the curve of 0.77 (95% CI, 0.69-0.85). There was no significant difference in cumulative fluid balance between the pulmonary edema and nonpulmonary edema groups. www.ccmjournal.org
1537
Editorials
Even though GEDI correlates with DCI and pulmonary edema in SAH patients, it is not yet ready to assume the role of the guardian for at-risk SAH patients as there are limitations to this study. This was an observational analysis with patients passively monitored once daily to obtain CEDI and ELWI measurements. Critical care clinicians recognize SAH patients are quite dynamic and assessing hemodynamic variables with limited frequency is fraught with peril. The absence or presence of pulmonary edema relied solely on ELWI and was not correlated with other subjective findings, such as hypoxemia, chest radiographs, or the need to institute diuresis. The SAH severity did not statistically correlate with occurrence of DCI which is contrary to estabhshed findings and weakens the ability to draw cause and effect conclusions. The area under the ROC for GEDI associated with DCI is only 0.66, suggesting one variable alone is not enough to fully explain the occurrence of DCI in at-risk patients, and there are likely many other factors influencing the outcomes once you adjust for GEDI. This study provides important fodder for further development of interventional trials to manage patients with aneurysmal SAH. It is clear targeting euvolemia is an important goal and developing standards based on dynamic cardiac variables rather than archaic static pressure measurements may allow those caring for the neurocritically ill to avoid the dark side of SAH. Perhaps, clinicians will evolve into GEDI masters while seeking the correct forces to avoid DCI.
REFERENCES 1. Kassell NF, Peerless SJ, Dunward QJ, et al: Treatment of ischémie deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery 1982; 11:337-343 2. Solomon RA, Post KD, McMurtry JG: Depression of circulating blood volume in patients after subarachnoid hemorrhage: Implications for the management of symptomatic vasospasm. Neurosurgery 1984; 15:354-361 3. Kosnik EJ, Hunt WE: Postoperative hypertension in the management of patients with intracraniai arterial aneurysms. J Neurosurg 1976; 45:148-154
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4. Lennihan L, Mayer SA, Fink ME, et al: Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage. Stroke 2000; 31:383-391 5. Egge A, Waterloo K, Sjaholm H, et al: Prophylactic hyperdynamic postoperative fluid therapy after aneurysmal subarachnoid hemorrhage: A clinical, prospective, randomized, controlled study. Neurosurgery 2001; 49:593-605 6. Diringer MN, BleckTP, Claude Hemphill J 3rd, et al; Neurocritical Care Society: Critical care management of patients following aneurysmal subarachnoid hemorrhage: Recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neuroerit Care 2011; 15:211-240 7. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology: Guidelines for the management of aneurysmal subarachnoid hemorrhage: A guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2012; 43:1711-1737 8. Rinkel GJE, Feigin VL, Algra A, et al: Circulatory volume expansion therapy for aneurysmal subarachnoid hemorrhage (review). Cochrane Database Syst Rev 2004; CD000483 9. Muench E, Horn P, Bauhuf C, et al: Effects of hypervolemia and hypertension on regional cerebral blood flow, intracraniai pressure, and brain tissue oxygénation after subarachnoid hemorrhage. Crit Care Med 2007; 35:1 844-1 851 ; quiz 1852 10. Dankbaar JW, Slooter AJ, Rinkel GJ, et al: Effect of different components of triple-H therapy on cerebral perfusion in patients with aneurysmal subarachnoid hemorrhage: A systematic review. Crit Care 2010; 14:R23 11. Hoft RG, van Dijk GW, Algra A, et al: Fluid balance and blood volume measurement after aneurysmal subarachnoid hemorrhage. Neuroerit Care 2008; 8:391-397 1 2. Marik PE, Baram M, Vahid B: Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008; 134:172-178 13. Osman D, Ridel C, Ray P, et al: Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med 2007; 35:64-68 14. Tagami T, Kuwamoto K, Watanabe A, et al; SAH PiCCC Study Group: Optimal Range of Global End-Diastolic Volume for Fluid Management After Aneurysmal Subarachnoid Hemorrhage: A Multicenter Prospective Cohort Study. Crit Care Med 2014; 42:1348-1356 15. Michard F, Alaya S, Zarka V et al: Global end-diastolic volume as an indicator of cardiac preload in patients with septic shock. Chest 2003; 124:1900-1908
June 2014 • Volume 42 • Number 6
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.
