Neurocrit Care DOI 10.1007/s12028-011-9589-5 REVIEW Hemodynamic Management of Subarachnoid Hemorrhage Miriam M. Treggiari • Participants in the International Multi-disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage Ó Springer Science+Business Media, LLC 2011 Abstract Hemodynamic augmentation therapy is con- the context of sparse data, no incremental risk of aneu- sidered standard treatment to help prevent and treat rysmal rupture has been reported with the induction of vasospasm and delayed cerebral ischemia. Standard triple- hemodynamic augmentation. H therapy combines volume expansion (hypervolemia), blood pressure augmentation (hypertension), and hemodi- Keywords Hemodilution Á Hypertension Á lution. An electronic literature search was conducted of Hypervolemia Á Inotropic Á Volume expansion English-language papers published between 2000 and October 2010 that focused on hemodynamic augmentation therapies in patients with subarachnoid hemorrhage. Introduction Among the eligible reports identified, 11 addressed volume expansion, 10 blood pressure management, 4 inotropic Delayed cerebral ischemia (DCI) is an important cause of therapy, and 12 hemodynamic augmentation in patients secondary neuronal injury after aneurysmal subarachnoid with unsecured aneurysms. While hypovolemia should be hemorrhage (SAH). Hemodynamic augmentation is the avoided, hypervolemia did not appear to confer additional mainstay of medical management among patients with benefits over normovolemic therapy, with an excess of side vasospasm. The natural history of circulating blood volume effects occurring in patients treated with hypervolemic after SAH is characterized by a reduction in blood volume targets. Overall, hypertension was associated with higher in patients undergoing surgery within 72 h of hemorrhage cerebral blood flow, regardless of volume status (normo- or [1]. Volume expansion and blood pressure manipulation hypervolemia), with neurological symptom reversal seen in can play an important role in maintaining cerebral blood two-thirds of treated patients. Limited data were available flow, particularly in setting of impaired autoregulation. In for evaluating inotropic agents or hemodynamic augmen- the experimental setting, as well as, following traumatic tation in patients with additional unsecured aneurysms. In brain injury, norepinephrine has been shown to be more predictable in maintaining cerebral perfusion pressure compared with dopamine [2, 3]. In patients with intact Participants in the International Multi-disciplinary Consensus autoregulation, dopamine has been shown to increase intra- Conference: Michael N. Diringer, Thomas P. Bleck, Nicolas Bruder, cranial pressure and cerebral blood flow, while no effect was E. Sander Connolly, Jr., Giuseppe Citerio, Daryl Gress, Daniel seen on cerebral hemodynamics with norepinephrine or Hanggi, J. Claude Hemphill, III, MAS, Brian Hoh, Giuseppe Lanzino, epinephrine [4]. However, it is unknown if data observed in Peter Le Roux, David Menon, Alejandro Rabinstein, Erich Schmutzhard, Lori Shutter, Nino Stocchetti, Jose Suarez, Miriam these settings extrapolate to the situation of ischemia in the Treggiari, MY Tseng, Mervyn Vergouwen, Paul Vespa, Stephan context of cerebral vasospasm, where there is likely to be at Wolf, and Gregory J. Zipfel. least regional impairment of autoregulation. In addition, enhancing cardiac performance in the context of hemody- & M. M. Treggiari ( ) namic augmentation after SAH might also be considered as a Department of Anesthesiology and Pain Medicine, University of Washington, Box 359724 Seattle, WA, USA strategy to reduce DCI. Hemodynamic management is e-mail: [email protected] often dubbed triple-H therapy, combining hypervolemia 123 Neurocrit Care from volume expansion, hypertension with blood pressure Summary of the Literature augmentation, and hemodilution through optimizing blood viscosity and oxygen-carrying ability. A total of 35 papers were included in this review, with most Although hemodynamic management is standard prac- papers addressing volume expansion therapy and blood tice in patients with SAH, limited data are available to pressure management. The only randomized trials included evaluate both the efficacy and safety of the different were two that focused on prophylactic hypervolemia [6, 7]. components of triple-H therapy for preventing or reducing vasospasm and DCI [5]. This review was designed to Volume Expansion Therapy evaluate available evidence for hemodynamic augmenta- tion after SAH by evaluating data for the treatment of A total of 282 unique references were identified during the patients with SAH using volume expansion therapy, initial PubMed and Embase search that addressed volume induced hypertension, inotropic agents, and hemodynamic expansion, with 52 identified in the secondary search and augmentation. from reference lists. A total of 11 studies were selected for review of volume expansion therapy data, including 2 randomized trials of prophylactic hypervolemia, although these did not specifically address treatment of established Methods vasospasm [6–16]. The first randomized controlled trial of prophylactic An electronic literature search was conducted by searching normovolemia versus hypervolemia found that hypervole- PubMed for data from the National Center for Biotech- mia did not increase blood volume or cerebral blood flow nology Information at the US National Library of Medicine (CBF) compared with normovolemia [6]. Likewise, there and Embase. An initial search was performed to identify were no differences in several other outcome measures English-language articles published between 2000 and including symptomatic vasospasm (20% in both groups), October 2010 using the key word ‘‘hemodynamics’’ and need for hypertensive hypervolemic therapy (17% vs. at least one of the following additional key words: ‘‘sub- 15%), infarction (17% vs. 10%), or complications com- arachnoid hemorrhage/drug therapy,’’ ‘‘subarachnoid paring the hypervolemia versus the normovolemia group, hemorrhage/surgery,’’ or ‘‘subarachnoid hemorrhage/ther- respectively. In contrast, an observational study of induced apy.’’ Titles and abstracts were reviewed to identify hypervolemic hemodilution in patients with documented candidate articles that addressed volume expansion ther- vasospasm found increased cardiac output, blood pressure apy, blood pressure management, inotropic agents, and and filling pressure, blood volume, and CBF after the ini- hemodynamic augmentation in patients with unsecured tiation of therapy [8]. In this study, the hemodynamic aneurysms. Secondary searches were performed to identify management called for more aggressive targets, including additional appropriate articles for each topic, using the daily fluid administration of 4–5 L, hematocrit target key word ‘‘subarachnoid hemorrhage’’ plus additional >29%, use of desmopressin to ensure positive fluid bal- terms: ‘‘hemodynamics,’’ ‘‘hemodilution,’’ ‘‘hypervole- ance, and systolic blood pressure >120 mm Hg. mia,’’ ‘‘hypervolemic,’’ ‘‘euvolemia,’’ or ‘‘euvolemic’’ for Egge et al. [7] conducted an open-label, randomized volume status; ‘‘blood pressure,’’ ‘‘agent,’’ ‘‘target,’’ controlled trial of 32 patients with SAH (Hunt & Hess ‘‘hemodynamics,’’ or ‘‘hemodilution’’ for blood pressure grades I–III) who were treated within 72 h of bleeding with management; ‘‘hemodynamics,’’ ‘‘hemodilution,’’ ‘‘inotro- normovolemia or triple H (hypervolemia, increase in mean pic,’’ or ‘‘hyperdynamic’’ for inotropic therapy; and arterial pressure by 20 mm Hg, and hematocrit 30–35%) ‘‘hemodynamics,’’ ‘‘hemodilution,’’ ‘‘unruptured aneu- for approximately 12 days. Several early and late endpoints rysm,’’ or ‘‘unsecured aneurysm’’ for hemodynamic aug- were measured. The occurrence of symptomatic vasospasm mentation in patients with unsecured aneurysms. (32% normovolemia vs. 25% triple H), transcranial Titles and abstracts of candidate articles were evaluated Doppler vasospasm (62% in both groups), and poor for possible inclusion. Citations were included if they were Glasgow Outcome Scale (GOS) at 1 year (13% normo- original data from studies that addressed treatment in volemia vs. 19% triple H) were not different between humans. Papers were excluded if they were reviews or the two groups. However, triple H was associated with commentaries, letters, case reports, duplicate data from higher rate of complications and higher cost, compared other studies, or not relevant to the topic of interest. with normovolemia. Additional references were sought by reviewing references In a prospective observational study, Muench et al. [9] lists from retrieved papers, recent review articles, and suggested that hypertension was associated with an systematic reviews for appropriate articles that might have increase in relative CBF and brain tissue oxygenation, been missed. irrespective of volume status (i.e., euvolemia vs. 123 Neurocrit Care hypervolemia and hemodilution, on days 1, 3, and 7 after myocardial infarction. These data need to be interpreted in the bleed). The brain oxygenation data are consistent with the context of a number of additional concomitant treat- the findings from Raabe et al. [10] who reported that, while ments, including no head of bed elevation and moderate and aggressive hypertension improved brain tis- administration of blood products, dextran, fludrocortisone, sue oxygen pressure values, hypervolemia was unlikely to atropine, pitressin, and digoxin. In a case series of four change brain