Critical Care Management of Patients Following Aneurysmal Subarachnoid Hemorrhage

30 Pages·2012·0.33 MB·English

NeurocritCare(2011)15:211–240
DOI10.1007/s12028-011-9605-9
REVIEW
Critical Care Management of Patients Following Aneurysmal
Subarachnoid Hemorrhage: Recommendations from the
Neurocritical Care Society’s Multidisciplinary Consensus
Conference
Michael N. Diringer • Thomas P. Bleck • J. Claude Hemphill III • David Menon • Lori Shutter •
Paul Vespa • Nicolas Bruder • E. Sander Connolly Jr. • Giuseppe Citerio • Daryl Gress •
Daniel Ha¨nggi • Brian L. Hoh • Giuseppe Lanzino • Peter Le Roux • Alejandro Rabinstein •
Erich Schmutzhard • Nino Stocchetti • Jose I. Suarez • Miriam Treggiari • Ming-Yuan Tseng •
Mervyn D. I. Vergouwen • Stefan Wolf • Gregory Zipfel
Publishedonline:20July2011
!SpringerScience+BusinessMedia,LLC2011
Abstract Subarachnoid hemorrhage (SAH) is an acute approachestomanagementandlimitedguidanceonchoos-
cerebrovasculareventwhichcanhavedevastatingeffectson ingamongthem.Existingguidelinesemphasizeriskfactors,
thecentralnervoussystemaswellasaprofoundimpacton prevention,naturalhistory,andpreventionofrebleeding,but
severalotherorgans.SAHpatientsareroutinelyadmittedto providelimiteddiscussionofthecomplexcriticalcareissues
anintensivecareunitandarecaredforbyamultidisciplinary involvedinthecareofSAHpatients.TheNeurocriticalCare
team. A lack of high quality data has led to numerous Society organized an international, multidisciplinary con-
sensusconferenceonthecriticalcaremanagementofSAHto
address this need. Experts from neurocritical care, neuro-
surgery, neurology, interventional neuroradiology, and
Disclaimer Thisstatementisprovidedasaneducationalserviceof neuroanesthesiologyfromEuropeandNorthAmericawere
theNeurocriticalCareSociety.Itisbasedonanassessmentofcurrent recruitedbasedontheirpublicationsandexpertise.Ajuryof
literatureandtheconsensusoftheopinionsoftheattendeesandjury
four experienced neurointensivists was selected for their
oftheconference.Itisnotintendedtoincludeallpossibleproper
methodsofcareforSAHpatients.Neitherisitintendedtoexclude experience in clinical investigations and development of
anyreasonablealternativemethodologies.TheNeurocriticalCare practice guidelines. Recommendations were developed
Societyrecognizesthatspecificpatientcaredecisionsarethe
based on literature review using the GRADE system, dis-
prerogativeofthepatientandthephysiciancaringforthepatient,
basedonallofthecircumstancesinvolved.Noformalpractice cussion integrating the literature with the collective
recommendationsshouldbeinferred.
experience of the participants and critical review by an
impartialjury.Recommendationsweredevelopedusingthe
TheOrganizer,MembersoftheJury,andConferenceparticipantsin
theInternationalMulti-disciplinaryConsensusConferenceonthe GRADEsystem.Emphasiswasplacedontheprinciplethat
CriticalCareManagementofSubarachnoidHemorrhagearelistedin
Appendix.
M.N.Diringer(&) L.Shutter
Neurology/NeurosurgeryIntensiveCareUnit,Washington UniversityofCincinnati,Cincinnati,OH,USA
University,St.Louis,MO,USA
e-mail:[email protected] P.Vespa
UniversityofCaliforniaatLosAngeles,LosAngeles,CA,USA
T.P.Bleck
RushMedicalCollege,Chicago,IL,USA N.Bruder
Universite´ delaMe´diterrane´e,Marseille,France
J.ClaudeHemphillIII
UniversityofCaliforniaatSanFrancisco,SanFrancisco, E.S.ConnollyJr.
CA,USA ColumbiaUniversity,NewYork,NY,USA
D.Menon
UniversityofCambridge,Cambridge,UK
123
212 NeurocritCare(2011)15:211–240
recommendationsshouldbebasednotonlyonthequalityof has been proven to improve outcome in prospective ran-
the data but also tradeoffs and translation into practice. domized controlled trials [1]. This lack of high quality
Strong consideration was given to providing guidance definitivedatahasledtonumerousapproachestomanage-
andrecommendationsforallissuesfacedinthedailyman- ment and provides limited guidance on choosing among
agementofSAHpatients,evenintheabsenceofhighquality them.
data. Therehavebeenrelativelyfewguidelinesdevelopedfor
SAH management. They emphasize risk factors, preven-
Keywords Subarachnoid hemorrhage Critical care tion, natural history, and prevention of rebleeding, but
! !
Aneurysm Vasospasm Anticonvulsants Hyponatremia provide limited discussion of the critical care issues
! ! ! !
Endovascular Fever involved inthecareofSAHpatients.Inordertoprovidea
!
comprehensive review of those issues the Neurocritical
Care Society organized a multidisciplinary consensus
Introduction conference on the critical care management of SAH.
Topicswerechosenbasedontheirrelevancetothecritical
Subarachnoid hemorrhage (SAH) is an acute cerebrovas- care management of patients with aneurysmal SAH. Pro-
cular event which can have devastating effects on the cedures used to repair aneurysms were not addressed.
central nervous system as well as a profound impact on
several other organs. The course of the disease can be Statement of Purpose
prolonged,withconsiderablesecondarybraininjurydueto
delayed cerebral ischemia (DCI). Systemic manifestations The purpose of the consensus conference was to develop
affectingcardiovascular,pulmonary,andrenalfunctionare recommendations for the critical care management of
common, and complicate the management of DCI. patients following acute SAH. The complex multi-organ
Duetotheprofoundeffectsofthehemorrhageitselfand pathophysiology of SAH presents a multitude of clinical
theriskofearlyrebleedingandhydrocephalus,SAHpatients challenges which demand attention. For each situation
areroutinelyadmittedtoanintensivecareunitandarecared decisions must be made about if, when, and how to inter-
for by a multidisciplinary team including neurosur- vene. Ideally, each decision would be made based on high
geons,(neuro) intensivists, (neuro) anesthesiologists and quality data; yet the reality is that such data rarely exist.
interventional neuroradiologists. The ICU course of SAH Still, decisions about management must be made. Recom-
patients ranges from afew days toa fewweeksand is fre- mendations were developed based on the literature, a
quentlyaccompaniedbymultiplemedicalcomplications. robust discussion regarding the interpretation of the liter-
Despite considerable effort, only one intervention—the ature, the collective experience of the members of the
useofnimodipine—forthiscomplexmultifaceteddisorder group and review by an impartial jury.
G.Citerio J.I.Suarez
SanGerardoHospital,Monza,Italy BaylorCollegeofMedicine,Houston,TX,USA
D.Gress M.Treggiari
UniversityofVirginia,Charlottesville,VA,USA UniversityofWashington,St.Louis,MO,USA
D.Ha¨nggi M.-Y.Tseng
Heinrich-HeineUniversity,Du¨sseldorf,Germany NottinghamUniversityHospitals,Nottingham,UK
B.L.Hoh M.D.I.Vergouwen
UniversityofFlorida,Gainesville,FL,USA UniversityofUtrecht,Utrecht,TheNetherlands
G.Lanzino A.Rabinstein S.Wolf
!
MayoClinic,Rochester,MN,USA FreieUniversita¨tBerlin,Berlin,Germany
P.LeRoux G.Zipfel
UniversityofPennsylvania,Philadelphia,PA,USA WashingtonUniversity,St.Louis,MO,USA
E.Schmutzhard
UniversityHospitalInnsbruck,Innsbruck,Austria
N.Stocchetti
FondazioneIRCCSCa` Granda–OspedalePoliclinico,Milan
University,Milan,Italy
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NeurocritCare(2011)15:211–240 213
Process Thejurymetfor2daysaftertheconferenceandagainat
a subsequent 2-day meeting and held several conference
Topicswereidentifiedbasedonclinicaldecisionpointsinthe calls. They reviewed selected key studies, the recommen-
criticalcaremanagementofSAHpatients.Expertsdrawnfrom dations made by the primary reviewers and the discussion
Europe and North America from the fields of neurosurgery, thattookplaceattheconference.Strongconsiderationwas
neurocritical care, neurology, interventional neuroradiology, given to providing guidance and recommendations for all
and neuroanesthesiology were recruited based on their issues faced in the daily management of SAH patients,
expertise related to each topic. A jury of four experienced even in the absence of high quality data.
neurointensivists was selected for their expertise in clinical
investigationanddevelopmentofpracticeguidelines.
Eachparticipantperformedacriticalliteraturereview.The Medical Measures to Prevent Rebleeding
findingsweresummarizedintablesandasummarywaspre-
pared which reviewed the data and provided specific Questions Addressed
managementrecommendations.Theseweresubmittedindraft
• Do any medical interventions reduce the incidence of
formbeforetheconferenceanddistributedtoallparticipants.
rebleeding in patients awaiting definitive management
The quality of the data was assessed and recommenda-
of their ruptured aneurysm?
tions developed using the GRADE system [2]. Thequality
• Do alterations in investigative approaches reduce the
of the evidence was graded as:
incidence of rebleeding in patients awaiting definitive
• High = Furtherresearchisveryunlikelytochangeour management of their ruptured aneurysm?
confidence in the estimate of effect. • Does stringent blood pressure reduction reduce the
• Moderate = Further research is likely to have an incidence of rebleeding in patients awaiting definitive
important impact on our confidence in the estimate of management of their ruptured aneurysm?
effect and may change the estimate.
• Low = Further research is very likely to have an
Summary of the Literature
important impact on our confidence in the estimate of
effect and is likely to change the estimate.
Rebleeding following aneurysmal SAH is common. Its
• Very low = Any estimate of effect is very uncertain.
incidence is highest immediately following the initial
TheGRADEsystemclassifiesrecommendationsasstrong hemorrhage (5–10% over the first 72 h) [3], is higher in
or weak, according to the balance among benefits, risks, patients with poor-grade SAH, larger aneurysms, sentinel
burden, and cost, and according to the quality of evidence. bleeds,andthosewhoundergocatheterangiographywithin
Keeping those components explicitly separate constitutes a 3 hoftheictus.Immediaterepairoftherupturedaneurysm
crucial and defining feature of this grading system. An by either coil embolization or microsurgical clip ligation
advantageoftheGRADEsystemisthatitallowsforstrong markedlyreducestheriskofrebleeding,withmicrosurgical
recommendationsinthesettingoflowerqualityevidenceand exclusionbeingslightlymoreefficacious[4].Nevertheless,
thusitiswellsuitedtothissituation.Recommendationswere some patients are either too sick for immediate repair or
eitherstrongorweakandbasedonthefollowing: requiretransporttoacenterwhererepaircanbeperformed.
Repair procedures have significant risks and require
• Thetrade-offs,takingintoaccounttheestimatedsizeof
experienced teams to minimize the serious procedural side
the effect for the main outcomes, the confidence limits
effects of repair. This fact can lead to further delay in
aroundthoseestimates,andtherelativevalueplacedon
repair, and increase the risk of rebleeding. We considered
each outcome
three interventions that might modulate this risk: antifi-
• The quality of the evidence
brinolytictherapy,catheter vs. CT angiography, andblood
• Translation of the evidence into practice in a specific
pressure control.
setting, taking into consideration important factors that
Nine studies of antifibrinolytic therapy prior to 2002
could be expected to modify the size of the expected
involving 1399 patients showed no benefit on poor out-
effects
come or death despite a marked significant reduction in
TheconferencetookplaceonOctober22–23,2010.Each rebleeding,probablyduetoasignificantlyhigherincidence
participant presented a summary of the data and recom- of cerebral ischemia in the treated patients [5]. It is note-
mendationstothejuryandotherparticipants.Presentations worthythatallofthesestudiescontinuedtherapyforweeks
were followed by discussion focused on refining the pro- (intotheperiodwhentheriskofvasospasmwashigh),and
posedmanagementrecommendations.Approximately1/3of at least one of these studies initiated therapy as late as
theconferencetimewasutilizedfordiscussion. 4 days post-ictus, when the risk of rebleeding was
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214 NeurocritCare(2011)15:211–240
substantially reduced. More recently, one randomized trial todetect an effect on functional outcome. Patients ingood
(involving 505 patients) [6] and two case control studies neurological condition with evidence of sentinel hemor-
(involving 428 patients) [7, 8] examined whether an early rhage,lossofconsciousnessatictusandwhoharborlarger
short course of antifibrinolytic therapy can reduce the risk aneurysms on initial CTA are likely to be the best popu-
of rebleeding while early, safe repair is being arranged. A lationforstudy.Thereappearstobesufficientequipoisein
third study also found a reduction in rebleeding but noted the USA for such a trial to be conducted, and we would
an increased incidenceof DVTs [8]. These studies suggest underline the fact that our recommendations in this area
a uniform reduction in rebleeding rates from *11 to wouldneedtoberevisedwhendatafromsuchastudywere
*2.5%, but the studies were not adequately powered to available.Giventheless-than-definitiveevidenceonwhich
determine the effect of antifibrinolytic therapy on overall we have based our recommendation for early antifibrino-
patient outcome. lytic therapy, we have explicitly stated several cautionary
Several case reports or case series report aneurysmal recommendations that would mitigate against side effects
rebleeding when catheter angiography is undertaken very of the intervention.
early(lessthan3–6 h)followinganeurysmalSAH.Specific We did not feel that the data available provided a clear
rebleedingratesaredifficulttocompute,asmanyoftheseare basis for attributing an increased rebleeding risk to ultra-
individual case reports, and the denominator in case series early DSA. Formal assessment of catheter vs. CT angiog-
(i.e.,the totalnumberofpatients undergoing early angiog- raphy in the hyperacute phase would require further
raphy)ispoorlydefined.However,ratesashighas20–38.5% collectionofepidemiologicaldatainthefirstinstance,and
havebeenquoted[9–13].Itseemsunwarrantedtoconclude alargetrialcomparingthetwowouldbeneededtoprovide
thisisaspecificriskattributabletoDSAforseveralreasons. definitive recommendations. Given that CTA is now well
First, where a clear denominator is provided to assess the established, it seems unlikely that a large RCT comparing
incidenceofrebleeding,figuresaremuchlower(*5%)[11]. DSAandCTAwillevermaterialize.However,pendingthe
Second, it is unclear whether these instances of rebleeding continued collection of epidemiological data, it was felt
with DSA actually reflect a risk of the procedure, or are that choosing CTA over DSA for ultra-early angiography
simplyamanifestationofthehighrebleedingratesknownto was a reasonable option where both options are available,
occur after initial aneurysm rupture. Third, there is no sat- the technical quality of CTA was good, and an endovas-
isfactorydirectcomparisonofrebleedingwithandwithout cular intervention was not planned at the time of
DSAortoCTAwithinthefirst6 hpost-SAH;theonecase angiography. However, in the setting of SAH, the over-
seriesthatdoesreportatwofoldriskwithDSAincludedonly whelming aim is to detect and secure a culprit aneurysm,
a small number of patients [12]. Intriguingly, reports of andthereisnocasefordelayinginvestigation(eitherCTA
contrastextravasationduringultra-earlyCTA[14,15]have or DSA) to reduce any theoretical risk of rebleeding.
heretoforebeeninterpretedastheinvestigationbeingableto There appears to be little concern that rebleeding with
imagetheprocessofearlyrebleeding[13],ratherthanbeing modest blood pressure elevation is a significant clinical
acauseofsuchrebleeding. issue, and there was no enthusiasm for a study addressing
Therearenosystematicdatathataddressbloodpressure this issue.
levelsinpatientswithunsecuredaneurysmsinrelationtothe
risk of rebleeding. Some early studies of hypervolemic–
Recommendations
hypertensive therapy reported aneurysmal rebleeding or
hemorrhagictransformationofhypodenselesionswithele- • Early aneurysm repair should be undertaken, when
vation of systolic blood pressure to 160–200 mmHg. possible and reasonable, to prevent rebleeding (High
However, more recent series do not report rebleeding at Quality Evidence; Strong Recommendation).
systolicbloodpressureinthisrange,andtheclearconsensus • Anearly,shortcourseofantifibrinolytictherapypriorto
of the participants at the workshop was that modest blood earlyaneurysmrepair(begunatdiagnosis;continuedup
pressure elevation (mean arterial pressure <110 mmHg; tothepointatwhichtheaneurysmissecuredorat72 h
systolic blood pressure <160 mmHg) was not associated post-ictus, whichever is shorter) should be considered
withrebleeding. (LowQualityEvidence;WeakRecommendation).
• Delayed(>48 haftertheictus)orprolonged(>3 days)
Discussion antifibrinolytictherapyexposespatientstosideeffectsof
therapy when the risk of rebleeding is sharply reduced
Further definitive evidence of benefit from antifibrinolytic and should be avoided (High Quality Evidence; Strong
agents will require a trial with very early identification of Recommendation).
patients and early administration of tranexamic acid or • Antifibrinolytic therapy is relatively contraindicated
aminocaproicacid,alargesamplesizeandsufficientpower in patients with risk factors for thromboembolic
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NeurocritCare(2011)15:211–240 215
complications (Moderate Quality Evidence; Strong [19, 20]. Thus, prophylactic anticonvulsant therapy with
Recommendation). phenytoin may worsen outcome, although the impact of
• Patientstreatedwithantifibrinolytictherapyshouldhave other anticonvulsant medications is less clear. Also, in
close screening for deep venous thrombosis (Moderate patients with no history of seizure, a short course (72 h)
Quality Evidence; Strong Recommendation). of anticonvulsant prophylaxis seems as effective as a
• Antifibrinolytic therapy should be discontinued 2 h more prolonged course in preventing seizures [21]. In
before planned endovascular ablation of an aneurysm comatose (poor-grade) SAH patients, non-convulsive sei-
(VeryLowQualityEvidence;WeakRecommendation). zures may be detected on continuous EEG (cEEG) in
• When CTAandDSA are both available andCTA isof 10–20% of cases [22–24]. While patients with non-con-
high technical quality, CTA should be performed vulsive seizures have a worsened outcome, the impact of
preferentially if endovascular intervention is not successful treatment of these non-convulsive seizures has
planned at the time of angiography (Very Low Quality not been studied. Also, the influence of anticonvulsant
Evidence; Weak Recommendation). prophylaxis on the occurrence of non-convulsive seizures
• Treat extreme hypertension in patients with an unse- has not been studied.
cured, recently ruptured aneurysm. Modest elevations
in blood pressure (mean blood pressure <110 mmHg)
Discussion
do not require therapy. Pre-morbid baseline blood
pressures should be used to refine targets; hypotension
There was general agreement among the participants that
should be avoided (Low Quality Evidence; Strong
current evidence raises concern that anticonvulsants, spe-
Recommendation).
cifically phenytoin, may worsen outcome after SAH.
Therefore, there was consensus that routine prophylactic
phenytoin use should not be undertaken after SAH. There
Seizures and Prophylactic Anticonvulsant Use was, however, controversy regarding use of other anti-
convulsant medications and the unknown potential for
Questions Addressed anticonvulsants to lessen the impact of non-convulsive
seizures. Also, the possibility that certain subgroups, such
• What is the incidence and impact of convulsive and
as elderly patients undergoing craniotomy, may have a
non-convulsive seizures after SAH?
higher seizure risk led the group to consider that a short
• Does anticonvulsant prophylaxis influence this
course(3–7 days)ofanticonvulsantprophylaxismightstill
incidence?
be considered in certain situations, especially if an agent
other than phenytoin was used. There was also agreement
Summary of the Literature that patients who suffer a clear clinical seizure after the
period of aneurysmal rupture should be treated with anti-
Abnormal movements that may appear seizure-like are convulsants, but that if seizures do not recur, these
common at the onset of SAH, but it is usually unclear anticonvulsants should be discontinued after 3–6 months.
whether this is a true seizure or represents posturing at the There was disagreement about whether an EEG should be
time of aneurysm rupture [16, 17]. Clinical seizures are performed at that time and, if so, whether seizure-free
uncommon after the initial aneurysm rupture (occurring in patients with an epileptic focus should be continued on
1–7% of patients) and when they occur in patients with an anticonvulsants. There was consensus that cEEG is prob-
unsecured aneurysm, they are often the manifestation of ably underutilized in poor-grade SAH patients and that
aneurysmal re-rupture [4, 18]. Risk factors for the non-convulsive seizures are common. However, there was
development of seizures in SAH are surgical aneurysm concern regarding whether these non-convulsive seizures
repair in patients >65 years of age, thick subarachnoid represented markers of disease severity or a target for
clot, and possibly intraparenchymal hematoma or infarc- treatment. Thus, there was modest disagreement on the
tion [16, 17]. Prophylactic treatment with anticonvulsants aggressiveness with which to pursue treatment of non-
in SAH patients without seizures has previously been convulsive seizures. There was a general agreement that
commonplace, although no randomized trials specifically one or perhaps two anticonvulsants should be used to
addressing this issue have been performed. Recent studies attempt to treat non-convulsive seizures identified on
have suggested that anticonvulsant use is associated with cEEG, but disagreement about whether to pursue more
worsened long-term outcome after SAH, although most of aggressive means such as benzodiazepine or barbiturate
the patients in these studies were treated with phenytoin infusions if initial measures were unsuccessful.
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216 NeurocritCare(2011)15:211–240
Recommendations [30]. Although several mechanisms have been proposed to
explain the cardiac abnormalities, the evidence seems
• Routine use of anticonvulsant prophylaxis with phe-
strongest for a catecholamine induced process [29]. Mon-
nytoin is not recommended after SAH (low quality
itoring of cardiac function may be beneficial in the setting
evidence—strong recommendation).
ofhemodynamicinstabilityormyocardialdysfunction,but
• Routine use of other anticonvulsants for prophylaxis
there is no evidence that it improves outcome. Manage-
may be considered (very low quality evidence—weak
ment of cardiac complications is heterogeneous, and
recommendation).
interventions should reflect current best medical practices.
• If anticonvulsant prophylaxis is used, a short course
Symptomatic pulmonary complications occur in over
(3–7 days) is recommended (low quality evidence—
20% of patients after SAH [31, 32], although evidence of
weak recommendation).
impaired oxygenation occurs in up to 80% [33]. These
• In patients who suffer a seizure after presentation,
complications are associated with worse clinical grade
anticonvulsants should be continued for a duration
SAH and higher mortality [34–36]. Patients may develop
defined by local practice (low quality evidence—weak
pulmonary edema (cardiac or neurogenic), acute lung
recommendation).
injury or acute respiratory distress syndrome. The mecha-
• Continuous EEG monitoring should be considered
nism of pulmonary injury may also be related to
in patients with poor-grade SAH who fail to
sympathetic hyperactivity or cardiac failure. Management
improve or who have neurological deterioration of
of pulmonary issues follows general principles of pul-
undetermined etiology (low quality evidence—strong
monary management, however, with careful attention to
recommendation).
avoid hypovolemia.
Discussion
Cardiopulmonary Complications
The participants all agreed that cardiopulmonary compli-
Questions Addressed cations are common after SAH, and have a significant
impact on clinical care. They frequently complicate
• What monitoring should be utilized in SAH patients
management by increasing procedural risk and exacerbate
with cardiovascular instability?
brain oxygen delivery by lowering perfusion pressure and
• Are there recommendations regarding managing car-
arterial oxygenation saturation. It was generally agreed
diopulmonary complications in patients with SAH?
that a baseline assessment of cardiac function with
echocardiography may be beneficial, especially if there
Summary of the Literature are any signs of myocardial dysfunction. Although there
is limited evidence, the panel strongly felt that cardiac
Myocardial injury occurs following SAHandis thoughtto output should be monitored (invasively or non-invasively)
be related to sympathetic stimulation and catecholamine in those patients with myocardial dysfunction or hemo-
discharge. Elevations of troponin I levels occur in dynamic instability.
approximately35%[25,26],arrhythmiasin35%[27],and Theparticipantsvoicedtheopinionthatmanagementof
wall motion abnormalities on echocardiography in about these complications may vary based on the patient’s clin-
25% of patients with SAH [28]. Echocardiographic ical status and in the setting of vasospasm. There was
abnormalities are more frequent in patients with elevated strong agreement that cardiopulmonary issues are wors-
troponin levels. The terms ‘‘Neurogenic Stress Cardiomy- enedintheeventofhypervolemia,thusthegoaloftherapy
opathy’’and‘‘StunnedMyocardium’’havebeenappliedto should be euvolemia. The panel also strongly recom-
the clinical syndrome of chest pain; dyspnea; hypoxemia, mended that management of cardiopulmonary issues
andcardiogenicshockwithpulmonaryedemaandelevated should reflect current best medical practice, while balanc-
cardiac markers that occurs within hours of SAH. This ing the needs of the underlying neurological condition.
syndrome has a wide spectrum of severity, and it may
contribute to sudden death in 12% of patients. The mani-
Recommendations
festationsareusuallytransientlasting1–3 daysafterwhich
myocardialfunctionreturnstonormal.Managementshould
Monitoring
focus on supportive care that balances cardiac needs with
the neurological goals [29]. • Baseline cardiac assessment with serial enzymes,
In general, cardiac abnormalities are more common in electrocardiography, and echocardiography is recom-
patients who later develop DCI and have worse outcomes mended, especially in patients with evidence of
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NeurocritCare(2011)15:211–240 217
myocardial dysfunction (Low quality evidence; Strong CVP appears to be an unreliable indicator of intravascular
Recommendation). volume [45, 46], and, although PACs may have a role in
• Monitoring of cardiac output may be useful in patients hemodynamically unstable patients, the complications
with evidence of hemodynamic instability or myocar- associated with their routine use appear to outweigh any
dial dysfunction. (Low quality evidence; Strong potential benefit [48–50].
Recommendation).
Discussion
Treatment
The participants generally agreed that volume status of
• Incaseofpulmonaryedemaorevidenceoflunginjury,the patientsshouldbemonitoredafterSAHeventhoughitmay
goal of therapy should include avoiding excessive fluid not accurately reflect intravascular volume, nor is there
intakeandjudicioususeofdiureticstargetingeuvolemia evidence that close monitoring has a beneficial impact on
(Moderatequalityevidence;Strongrecommendation). outcome.
• Standard management ofheart failure is indicated with The panel discussed multiples methods to monitor vol-
the exception that CPP/MAP should be maintained as ume status, and weighed the evidence regarding potential
appropriate for the neurological condition. (Moderate risk versus benefit of each. It was generally felt that both
quality evidence; Strong recommendation). physical findings and clinical data must be integrated into
assessment of volume status. Although there was not a
preferred method of monitoring volume status, a hierar-
chical approach is often used. The primary assessment
Monitoring Intravascular Volume Status
shouldbeclosemonitoringoffluidinputandoutput.Other
invasive and non-invasive modalities may be used to pro-
Questions Addressed
vide supplemental information based on the clinical
• Whatistheroleofmonitoringfluidbalanceandcentral scenario, but no one tool should be used in isolation. The
venous pressure (CVP)? paneldidvoicestrongagreementagainsttheroutineuseof
• What measurements should be used to assess blood invasive PACs or dependence on CVP targets.
volume?
• Is there a role for non-invasive hemodynamic Recommendations
monitoring?
• Monitoring of volume status may be beneficial (Mod-
• Is there a role for pulmonary artery catheters (PACs)?
erate quality evidence; weak recommendation).
• Vigilant fluid balance management should be the
Summary of the Literature foundation for monitoring intravascular volume status.
While both non-invasive and invasive monitoring
SAH patients frequently develop hypovolemia and hypo- technologies are available, no specific modality can
natremia. Retrospective studies have identified a be recommended over clinical assessment (Moderate
relationship between hypovolemia and an increased inci- quality evidence; weak recommendation).
dence of cerebral infarcts and worse outcome [37, 38]; • Central venous lines should not be placed solely to
especially when fluid administration is restricted. For this obtain CVP measures and fluid management based
reason,assessmentofintravascularvolumeinpatientsafter solely on CVP measurements is not recommended
SAHisessentialtodailymanagement.Therefore,guidance (Moderate quality evidence; strong recommendation).
is needed regarding the mechanism and impact of altera- • Use of PACs incurs risk and lacks evidence of benefit.
tions in fluid balance, and the methods for monitoring Routine use of PACs is not recommended (Moderate
volume status. Available literature describes multiple fac- quality evidence; strong recommendation).
tors that may contribute to changes in volume status
[39, 40].
Fluid balance may not accurately reflect intravascular
Managing Intravascular Volume Status
volume [41–44], therefore invasive and non-invasive
methodshavebeenusedaspossiblealternativestomonitor
Questions Addressed
volume status. Although all methods provide information
to guide patient management, none have demonstrated • Should prophylactic hypervolemia be employed in the
superiorityovervigilantfluidmanagement[45–47].Infact, management of SAH patients?
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218 NeurocritCare(2011)15:211–240
Summary of the Literature Recommendations
• Intravascular volume management should target eu-
There appears to be a defect in regulation of intravascular
volemia and avoid prophylactic hypervolemic therapy.
volumefollowingSAHwhichcanresultinhypovolemiain
In contrast, there is evidence for harm from aggressive
a significant number of patients and is associated with
administration of fluid aimed at achieving hypervole-
worse outcome [39, 51, 52]. Early reports suggested that
mia (high quality evidence; strong recommendation).
prophylactic hypervolemia and augmentation of blood
• Isotonic crystalloid is the preferred agent for vol-
pressure could raise cerebral blood flow in SAH patients
ume replacement (Moderate quality evidence; weak
[53]. These observations raised the possibility that a
recommendation).
management strategy of aggressive fluid administration
• In patients with a persistent negative fluid balance, use
targeted to achieve hypervolemia might be beneficial.
offludrocortisoneorhydrocortisonemaybeconsidered
Two prospective randomized controlled trials investi-
(moderate quality evidence; weak recommendation).
gated the use of prophylactic hypervolemic therapy after
surgical repair of the ruptured aneurysm [54, 55]. Central
venous or pulmonary capillary wedge pressure targets
were used to guide therapy. Neither study found any Glucose Management
benefit in terms of CBF, TCD defined vasospasm or
clinical outcome. These studies and others [56, 57], Questions Addressed
however, identified an increased incidence of complica-
• Is there an optimal serum glucose concentration range
tions, primarily pulmonary edema, associated with
after SAH that avoids secondary brain injury?
hypervolemic therapy.
• Does maintenance of that range with insulin infusions
In a prospective observational study a rise in regional
improve outcome over liberal glucose management?
CBFandbrainoxygentensionwereseenwithprophylactic
• Does cerebral glucose concentration on microdialysis
hemodynamicaugmentation [56];the beneficial effectwas
provide better information than serum glucose regard-
attributed entirely to induced hypertension rather than
ing optimal management?
hypervolemia.
Although primarily targeted at the correction of hypo-
natremia, a number of small randomized trials provide Summary of the Literature
information about the impact of fludrocortisone and
hydrocortisone on volume status. They indicate that these Hyperglycemia is commonly identified during initial
agents appear to reduce the volume of fluids needed to evaluation of patients with SAH [63]. Numerous retro-
maintain euvolemia [58–62]. spective observational studies have found that admission
hyperglycemiaisassociated withpoorerclinical gradeand
Discussion worsened outcome [64–66]. However, in some studies,
this effect was not significant when adjusting for clinical
There was broad agreement among the participants that condition and amount of subarachnoid blood. Although
hypovolemia was to be avoided following SAH. The there have not been any randomized controlled clinical
prospective studies comparing prophylactic hypervolemia trials of tight versus liberal glucose management in SAH,
and euvolemia were regarded as convincing evidence for several observational studies have reported on SAH
lack of benefit for prophylactic hypervolemia. There was patients who were managed clinically according to vari-
general agreement that there were significant cardiopul- ous target glucose regimens, including several which used
monary complications associated with prophylactic insulin infusions [67–69]. Liberal glucose management
hypervolemia. (>220 mg/dl) is associated with increased infection risk,
Discussion turned to the potential use of mineralo- or although patients in the main study with this finding
gluco-corticoids to prevent the development of hypovol- received dexamethasone as part of clinical care [68]. One
emia. Prospective randomized controlled trials of study found improved outcomes in patients successfully
hydrocortisone and fludrocortisone to prevent hyponatre- treated to a target glucose range of 80–140 mg/dl [70].
mia in SAH suggest that those agents may reduce the Hyperglycemia has been associated with occurrence of
amountoffluidrequiredtomaintaineuvolemia.Therewas vasospasm [71]. A study of SAH patients treated with
support for their use in patients with excessive diuresis; insulin infusions to maintain tight glucose control
however, this was tempered by concern about the impact (80–110 mg/dl) found an increase in episodes of hypo-
on glucose control from the high dose of hydrocortisone glycemia, and this was associated with more vasospasm
employed in the studies. and less favorable 3-month outcome [72]. There have also
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NeurocritCare(2011)15:211–240 219
been reports of cerebral microdialysis findings of cerebral Summary of the Literature
metabolic crisis and low cerebral glucose in SAH patients
being treated with insulin infusions, even in the absence Feverisreportedtooccurin41–72%ofpatientsfollowing
of systemic hypoglycemia [73, 74]. Current methods for SAH and is more common in patients who are poor-grade
assessing serum (or cerebral) glucose are intermittent and [76–78], have more subarachnoid blood and have intra-
do not provide continuous measurements. ventricular blood. In experimental models of cerebral
ischemia higher temperature is associated with larger
Discussion infarcts and worse outcome. Retrospective studies in SAH
patientshaveconsistentlyfoundthatfeverisindependently
There was general agreement that extreme systemic associated with poor outcome [76, 79–81]. Infarcts are
hyperglycemiaisbothamarkerofseverityofSAHaswell more common in febrile patients. Temperature elevation
as a risk factor for infection. There was concern that appearstobepartofasystemicinflammatoryreactionthat
aggressivecontrolofserumglucoseusinginsulininfusions is frequently not infectious in origin. The strongest pre-
could result ininappropriatelylow cerebralglucose levels, dictors of fever are poor Hunt–Hess grade and
and that in most situations, this would go undetected intraventricular hemorrhage (IVH) [82, 83]. Febrile epi-
because microdialysis is not widely available as a clinical sodes may be associated with microdialysis values that
managementtool.Therewasalsoconcernthatlowcerebral suggest metabolic stress which reverse with reduction in
glucoselevelsmayoccureveninthesettingoflow-normal temperature [84].
serum glucose levels. There was also recognition that Suppressionofinfectiousfever,however,hasrisk.Fever
systemic hypoglycemic events are more common with is an adaptive host response to infection. In a number of
insulin infusions, especially with a tight target glucose different clinical settings treatment of fever results in a
range, and that the NICE-SUGAR trial found worsened prolonged course of illness [85, 86]. No study has pro-
outcomeinpatientstreatedwiththisregimen(althoughnot spectively addressed the impact of fever control on
specific to SAH) [75]. Thus, the group felt that hypergly- neurologic injury, infection or outcome in SAH patients
cemiawasacommonoccurrenceandasignificantconcern, [87].
but that a specific target serum glucose range to minimize The efficacy of different methods of treating fever has
secondary brain injury after SAH was not known and been assessed in a number of studies. Acetaminophen and
current methods of intermittent assessment of serum glu- ibuprofen are not very effective, as they normalize tem-
cose were probably insufficient for adequate glucose peratureinonlyaminorityofpatients[88,89].Continuous
control management. infusions of NSAIDs may be more effective [90]. Use of
fanning, evaporative cooling, sponging, ice packs, cooling
blanket are often ineffective.
Recommendations
Newer surface and intravascular devices to treat fever
• Hypoglycemia (serum glucose <80 mg/dl) should be havealsobeenintroduced[91].Inprospectiverandomized
avoided (High quality evidence-strong recommenda- controlled trials intravascular devices were more effective
tion). at controlling fever than conventional means in SAH
• Serum glucose should be maintained below 200 mg/dl patients [92]. A similar degree of efficacy has been dem-
(Moderate quality evidence-strong recommendation). onstrated for surface devices [93]. In a small study
• If microdialysis is being used, serum glucose may be intravascular methods maintained a more stable tempera-
adjusted to avoid low cerebral glucose (Very low ture when compared to water circulating gel-coated pads
quality evidence-weak recommendation). [94].
Aggressive means to control fever can cause shivering.
The metabolic consequences include a marked increase in
resting energy expenditure, carbon dioxide production,
Management of Pyrexia
systemicoxygen consumption[95]andadecrease inbrain
tissue oxygen tension [84]. A number of measures have
Questions Addressed
been employed to reduce shivering including counter-
• Should measures be used to suppress fever in SAH warmingofextremitiesandtheuseofmedicationssuchas
patients? During what time period? buspirone, magnesium, meperidine, propofol as well as
• What methods are available? other sedatives. The absolute and relative efficacy of these
• How should shivering be managed? different measures is unknown.
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220 NeurocritCare(2011)15:211–240
Discussion firstlineoftherapy(Moderatequalityevidence—strong
recommendation).
There was wide agreement among the participants that • Surface cooling or intravascular devices are more
suppression of fever was appropriate in SAH patients at effective and should be employed when antipyretics
risk for or with active DCI. Although only effective in a fail in cases where fever control is highly desirable
minority of patients, all agreed that first step in fever (High quality evidence—strong recommendation).
controlwastheadministrationofantipyretics.Concernwas • Use of these devices should be accompanied by
raised regarding the antiplatelet effects of ibuprofen and monitoring for skin injury and venous thrombosis
other NSAIDs in patients who had undergone cranioto- (Weak quality evidence—strong recommendation).
mies.Inthediscussionthatfolloweditbecameevidentthat • Patients should be monitored and treated for shivering
the majority of those present were comfortable adminis- (High quality evidence-strong recommendation).
teringNSAIDsforfevercontrolfollowingcraniotomy.The
use of intravenous infusion of NSAIDs was discussed as
potentially being more effective than intermittent doses.
Deep Venous Thrombosis Prophylaxis
Many of theparticipants reportedroutine use ofsurface
and intravascular devices to control fever. All agreed they
Questions Addressed
were more effective in eliminating fever and maintained
the target temperature more consistently. There was con- • Should prophylaxis for deep venous thrombosis be
siderable discussion regarding the shivering they induce. performed after aneurysmal SAH?
Concern was raised regarding the catecholamine release, • What is the best agent?
riseinoxygenconsumptionandmetabolicstresscausedby • What is the optimal timing?
shivering. Most centers using cooling devices routinely
employed measures to minimize shivering, starting with
Summary of the Literature
surface counter-warming. Additional pharmacologic mea-
sures were often required using a variety of agents.
SAH induces a prothrombotic state that may lead to the
Because of their modest impact on level of consciousness,
development of deep venous thrombosis (DVT) and pul-
buspirone and magnesium were preferred by some, others
monary embolism. The incidence of DVT in SAH ranges
routinely used meperidine.
from 1.5 to 18%, with the higher incidence being demon-
The use of surface as opposed to intravascular devices
strated using prospective lower extremity ultrasound
varied across centers. Intravascular devices appear to
screening in a large cohort [97, 98]. Poor-grade SAH
maintain a more stable temperature but there are insuffi-
patientsappeartohavethehighestratesofDVT.Thecon-
cient data to compare the two approaches in terms of
ventional methods for DVT prophylaxis in SAH patients
shiveringandcomplications.Acomparisonofthemethods
include the use of mechanical methods such as sequential
in another clinical condition, coma after cardiac arrest,
compression devices (SCDs), and medical treatments
found no important differences in their performance,
including unfractionated heparin, low molecular weight
shivering and other complications [96]. There were some
heparin,ornon-heparinoidanticoagulantagents.Inameta-
reports of thrombosis formation associated with intravas-
analysis, SCDs, unfractionated heparin and low molecular
cular devices but other frequent users had not noted any
weightheparinweresimilarlyeffectiveinpreventingDVTs
association.
[99].Therewasatrendtowardhigherratesofintracerebral
hemorrhage and non-cerebral minor hemorrhage with low
Recommendations
molecular weight heparin as compared with SCDs or
• Temperature should be monitored frequently; infec- unfractionatedheparin[99].ThetimingofDVTprophylaxis
tious causes of fever should always be sought and inrelationshipwithaneurysmocclusioniscontroversial,but
treated (High quality evidence—strong recommen- typically prophylactic medications are withheld until the
dation). aneurysmhasbeeneitherclippedorcoiled.
• During the period of risk for DCI control of fever is The risk of brain hemorrhage appears to be dependent
desirable; intensity should reflect the individual on the agent used. The highest risk of hemorrhage appears
patient’s relative risk of ischemia (Low quality evi- to be with low molecular weight heparin, and the lowest
dence—strong recommendation). riskwithSCDs[99].ThedurationofDVTprophylaxishas
• While the efficacy ofmostantipyretic agents (acetami- notbeenstudied.Theperiodofgreatestriskfordeveloping
nophen, ibuprofen) is low, they should be used as the DVT is not presently known.
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