LongTerm Outcome Call into Question the Benefit o

Authors: Andrea Orfanakis Ansgar M Brambrink

Publish Date: 2013/09/11

Volume: 19, Issue: 2, Pages: 137-139

PDF Link

Abstract

Aneurysmal subarachnoid hemorrhage SAH has a high mortality and morbidity and longterm outcome is determined by the functional capacity of the patient Preventing delayed cerebral ischemia that will result in delayed ischemic neurological deficits DINDs is a paramount treatment goal during the posthemorrhage period There is still controversy regarding the best strategies While therapeutic induction of hypertension hypervolemia and hemodilution “TripleH therapy” is the most commonly accepted treatment uncertainty remains among others whether colloids versus crystalloids should be utilized and whether maintaining a positive fluid balance in patients with evidence for vasospasm improves longterm functional outcomeIbrahim and Macdonald 1 approached the problem by conducting a posthoc analysis of an existing large database n = 413 CONSCIOUS1 trial 2 First they used propensityscore matching to determine whether the administration of colloids between days 3 and 14 period of the highest risk for cerebral vasospasm/DIND after SAH influences the incidence of DIND and of delayed infarction and whether it influences the functional outcome 6–12 weeks after SAH Glasgow outcome scale modified Rankin scale mRs and NIH stroke scale NIHSS Next using a multivariate logistic regression model they evaluated any association that an overall fluid balance during the DIND risk period 3–14 days has on the same outcome parameters They found that treatment with colloids during the DIND risk period does not reduce the risk for DIND or delayed cerebral infarcts but that it rather was associated with worse functional outcomes NIHSS Equally important they found that a positive fluid balance during the DIND risk period was associated with prolonged length of stay in the ICU and worse functional outcome mRS at 12 months after SAH However they also found that patients with angiographic evidence of severe vasospasm had more delayed cerebral infarcts when their fluid balance remained negative during the DIND risk period The authors conclude that the volume status of patients after SAH should be managed carefully and colloids should be restricted to selected patients and administered only under careful monitoringFirst over the last several years in the medical literature studies have surfaced regarding the negative effects of IV fluid overresuscitation This includes both positive fluid balance per day over an extended period of time during the hospitalization as well as high “throughput” of IV fluids in the setting of an even fluid balance It is now well documented that both management strategies are harmful in patients with sepsis ARDS after trauma or during the perioperative period 3 4 5 6 7 8 9 However the exact mechanism remains unclear The new results presented by Ibrahim and Macdonald 1 suggest that equally the injured brain may not be immune to the negative effects of fluid overadministration Their results are particularly important as it has been considered a gold standard of therapy to induce and maintain positive IV fluid balance in patients after SAH during the window of vasospasm in order to prevent DIND Interestingly enough the data suggest that even in the context of clinical signs of DIND hemodilution/hypervolemia ie a positive fluid balance even as a rescue therapy does not protect against neuronal damage but rather is detrimental in the immediate hospital period as well as to the longterm functional outcomeSecond Ibrahim and Macdonald 1 found that treatment with colloids during the DIND risk period was not neuroprotective but in fact negatively influenced the longterm functional outcome of patients after SAH Also they found that treating with colloids did not change the net fluid balance compared to a straight crystalloid treatment regime It would have been very interesting to understand whether this is true for all types of colloids Plasma hetastarch and albumin are very different substances with unique effects on multiple organ systems The authors decided to group the outcomes following the use of all three of these substances which precludes such discussion based on their dataset The literature on the negative effects of plasma administration for other organ systems than the brain is prominent today 10 and further research will be necessary to address this clinical question and to understand whether SAH patients can safely receive any colloid during their treatment period in the ICUThird the traditional thinking is to avoid a negative fluid balance in SAH at all costs which invariably leads to high IV fluid “throughput” The data presented by Ibrahim and Macdonald 1 support such practice when patients have angiographic evidence of severe cerebral vasospasm Under those condition patients are at a higher risk for delayed cerebral infarcts and a negative fluid balance increases that risk according to their data However this is a small subgroup of patients after SAH Many patients do not have angiographic evidence of severe cerebral vasospasm and Ibrahim and Macdonald’s data suggest that for these patients inducing and maintaining hypervolemia during the first 2 weeks of their hospitalization does not protect against unfavorable outcomes like delayed neurologic deficit or delayed cerebral infarction but is rather harmful Moreover fluid treatment that aims for hypervolemia in this patient population is usually heavily based on isotonic or hypertonic salt solutions This practice results in a higher incidence of hyperchloremic metabolic acidosis a pathophysiologic state which is also gaining interest in its ability to do harm to various tissue groups of the body 6 11Fourth the commonly held belief in therapeutic use of triple H therapy has come under question in the recent years Two RCTs have touched on the risks of hypervolemia in SAH However both trials were underpowered but their results were nevertheless thoughtprovoking 12 It is a positive development when fixed belief systems and “commonly held” practices undergo reevaluation by the scientific community on a routine basis It was therefore timely that Ibrahim and Macdonald set out to determine if tripleH therapy is beneficial to all aneurysmal SAH patients during the DIND risk period The next step though would be to further investigate the pathophysiology of DIND in the light of the new findings and concerns It remains for example unknown whether there is a direct causal relationship between cerebral vasospasm and delayed neuronal deficit or delayed neuronal infarction Large vessel and small vessel spasm may not result from the same mechanism nor do they likely have the same mechanism to cause functional deficit or morphologic brain injury Among others putative processes such as cortical spreading ischemia and activation of specific inflammatory pathways are currently topics for intense research 13 14 Contributions from the laboratory will likely guide new therapeutic approaches in this fieldFinally before the complex pathophysiology of delayed neurologic injury can be better understood Ibrahim and Macdonald 1 based on their findings are supporting clinicians in a judicious IV fluid management strategy of SAH patients during highrisk period for DIND Moreover not all patients after aneurysmal SAH are at equal risk for delayed neuronal injury Therefore not all patients need to be managed equally and the presented data will also support clinicians when tailoring therapies to select patients rather than treating all patients the same who present with this potentially devastating disease

Keywords: