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REVIEW ARTICLE | |
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Surgery for spontaneous intracerebral hemorrhage: Emerging trends
Girish Menon
Department of Neurosurgery, Kasturba Medical College, Manipal, Karnataka, India
Date of Web Publication | 16-Jun-2017 |
Correspondence Address:
Girish Menon
Department of Neurosurgery, Kasturba Medical College, Manipal – 576 104, Karnataka
India
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/amhs.amhs_42_17
In spite of advances in imaging and surgical techniques, spontaneous intracerebral hemorrhage (SICH) has defied attempts to find a scientifically proven effective therapy. The pathophysiology of SICH suggests that early removal of the clot with minimal additional surgical trauma should prove beneficial. Trials in this direction have been few, and for some unknown reason, surgery has not proved to be superior to best medical management in most of these trials. This has led to substantial variability in the management of ICH throughout the world, and the treatment of SICH remains a controversy. SICH encompasses spectra of possible clot locations with varying volumes. Surgery so far has been reserved only for patients with large hematomas and impending brain herniation. Critical analysis of the earlier studies has now shown that surgery does help in clots in certain locations and of particular volume and when done at an optimal time. Poor grade patients with large hematomas, earlier considered poor surgical candidates are being taken up for aggressive decompressive craniectomies with fair results. In addition, minimally invasive surgical techniques complemented by thrombolytic techniques seem to providing surprisingly good results. Overall surgery seems to be going through a period of renaissance with respect to primary spontaneous ICHs.
Keywords: Craniotomy, decompressive craniectomy, spontaneous intracerebral hemorrhage
How to cite this article: Menon G. Surgery for spontaneous intracerebral hemorrhage: Emerging trends. Arch Med Health Sci 2017;5:65-70 |
Introduction |
Spontaneous intracerebral hemorrhage (SICH) refers to a blood clot in the brain parenchyma without a history of a preceding trauma or surgery. SICH affects 10–20 in 100,000 people every year and accounts for 20%–30% of all strokes.[1],[2],[3],[4] SICH is associated with a 30-day mortality rate of 32%–50% and only 10% become functionally independent at long-term follow-up.[2],[4],[5] SICH can be primary or secondary to underlying etiologies such as aneurysms, vascular malformations, vasculitis, etc. Management of secondary SICH is essentially targeted toward the correction of the underlying etiology to prevent further bleeds. Hypertensive arteriolosclerosis and amyloid angiopathy account for nearly 80% of primary SICHs.[2],[3],[4] The common sites for a primary ICH are basal ganglia and internal capsule (35%–70%), brainstem (5%–10%), and cerebellum (5%–10%). Lobar ICH accounts for the remaining one-third of bleeds and is often related to amyloid angiopathy.[3],[4],[5],[6] This review attempts to provide a brief review on the current status of the role of surgery in the management of primary SICH.
Review of earlier trials
Multiple trials and studies have tried to address the role of surgery in primary ICH, the most notable among them being the Surgical Trial in ICH (STICH) trials.[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23] Most of the other studies, however, have been small case series and surprisingly, only 14 planned and systematic trials have been conducted, and a total of <5000 patients have been studied as part of a trial so far on this rather common medical emergency.[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19],[20],[21],[22],[23]
The first randomized trial was published in 1961 (McKissock) and suggested that there was no significant advantage for surgery. It was only in 2000 that Fernandes et al. in 2000, suggested benefit from surgery with a reduction in death and dependency by a factor of 0.63.[22] The landmark trial titled “The Surgical Trial in Intracerebral Hemorrhage” (STICH trial) was undertaken by Prof. Mendelow et al. to determine whether early surgery reduces mortality and improves neurological outcome compared with conservative management for supratentorial ICH when the treating neurosurgeon was in doubt regarding the ideal management strategy.[7] The STICH trial randomized 1033 patients with supratentorial hemorrhage (lobar or ganglionic hematoma) to early surgery (within 96 h of ictus) versus standard of care (i.e., medical management with delayed surgery if necessary). A fair summary of STICH I trial is that except for possibly those with superficial ICHs, craniotomy at 1 day or longer after onset is not better than standard of (medical management with delayed surgery if necessary). However, the study observed a nonsignificant absolute benefit of 5% in favor of early surgery Rankin Scale at 6 months follow-up. Another interesting observation was that the subgroup of patients with superficial ICHs (lobar hemorrhage within 1 cm of the cortical surface) who underwent surgery was found to have better outcomes.[7] This result prompted a second trial STICH II, for patients with superficial lobar hematomas (10–100 ml). STICH II too found no difference in mortality or severe disability with early surgery (P = 0.37).[8] The two STICH trials were subjected to widespread criticisms, especially with regard to timing of surgery, large crossovers from medical arm to surgical arm, and the fact that minimally invasive techniques were hardly used (Only 6% of patients had surgery within 8 h of ictus; whereas mean time to surgery was 64·2 h). These facts notwithstanding, the two STICH trials and few subsequent trials have had a profound negative effect on the role of surgery in SICH prompting the American Heart Association to conclude that for most patients with supratentorial ICH, the usefulness of surgery is not well established (Class IIb; Level of Evidence A.).[1]
Why surgery?
The exact pathophysiology for neurological deterioration following an intracerebral bleed is unclear. The possible mechanism includes the mass effect due to the volume of the clot, the toxins liberated by the degrading blood products, the ischemia surrounding the clot, the intraventricular bleed and secondary hydrocephalus if any.[6] Logical reasoning, therefore, would suggest that removal of the clot should reduce edema and intracranial pressure (ICP), limit ischemia, and prove beneficial. Surprisingly, complete evacuation of the clot does not translate into neurological improvement, and most of the trials done so far have failed to clearly establish the efficacy of surgery.
Why have repeated trials failed to prove the efficacy of surgery?
Surgical trauma to an already traumatized brain and risk of fresh bleeds could possibly explain the lack of benefits following surgery. Another hypothesis is that a hitherto unrecognized mechanism akin to posttraumatic diffuse axonal injury probably plays an important role in determining the neurological status following a bleed.[24],[25] It is possible that the repercussions following a sudden rupture of the blood vessel are not limited to the adjacent area but felt diffusely throughout the brain. The third question is whether we are interpreting the trial results right?
Critical analysis of the earlier trials
The STICH trial design had several drawbacks.[7] Equipoise on the role of surgery in the mind of the treating neurosurgeon was a mandatory requirement. Patients with large hematoma and features of herniation who underwent emergency surgery were naturally not captured in this study. Moreover, the trial design provided an option of waiting for surgical intervention until the patient deteriorates. Surgical arm thus comprised a significant number of patients taken up for surgery postdeterioration which skewed the final observations. STICH II trial on lobar bleeds observed that patients with predicted poor prognosis at enrollment were more likely to have a favorable outcome with early surgery than those patients with predicted good prognosis at enrollment (odds ratio [OR] 1.12, P = 0.57).[8] The poor outcome of patients with good prognostic indicators at enrollment could have been due to delayed recruitment for surgery. The STICH trial design thus reflects the clinical reality that in case of deterioration and imminent death, most surgeons prefer to operate and surgeries done on an emergency basis are seldom captured and reported.
SICH includes clots of various dimensions at various sites in patients of different age groups with different comorbidities and presenting to the neurosurgeon at varying time intervals after the ictus. A major fallacy of earlier trials was not accounting for these individual variables. A subgroup analysis of all these variables was attempted by Gregson et al. to pool all available original data from all available surgical trials to carry out an individual patient data meta-analysis.[26] The meta-analysis concluded that outcome is better if surgery is done within 8 h of ictus (P = 0.003), volume of the hematoma is 20–50 ml.(P = 0.004), Glasgow coma scale (GCS) is between 9 and 12 (P = 0.0009), patient is aged between 50 and 69 (P = 0.01), and the hematoma is superficial with no intraventricular hemorrhage (IVH) (P = 0.09) 10. A Cochrane review from 2008 by Prasad et al. including ten randomized controlled trials (RCTs), including the STICH trial concluded that surgical evacuation added to best medical management reduces mortality and disability.[27] Prasad et al. in conclude that surgery significantly reduces the odds of being dead or dependent at final follow-up (OR 0.71, 95% confidence interval [CI] 0.58–0.88; 2P = 0.003 (no significant heterogeneity [P = 0.22; I2 = 24.7%]).[27] In sharp contrast to the previous studies, a recent report by Zheng et al. suggests that patients with hematoma >40 ml are more likely to have favorable outcome with surgery (13% vs. 0%, P = 0.005) and so do patients with IVH (16.6% vs. 7.2%, P = 0.03).[23] In yet another recent study analyzing significant prognostic factors in surgically treated patients, Maila found male patients below 60 years with right basal ganglionic bleeds of volumes <70 ml and an admission GCS above 8 to carry a good prognosis, especially if surgery was carried out within 24 h of ictus.[28]
Compiling available literature evidence it would be reasonable to suggest that surgery could reduce the short-term and long-term mortality in patients with SICH.[26],[27],[28] Overall, surgery may not be superior to best medical management, but there exists a subgroup of patients who definitely benefit with surgery carried out at an optimal time. Surgery is not going to change the final Rankin scale mRS (outcome) and deficits may or may not improve depending on the plasticity. However, surgery will help to reach the final mRS faster, will help in early rehabilitation, will reduce Intensive Care Unit stay and hospital stay, and may give a chance for poor grade patients to survive.
Which are the patients who benefit from surgery
Age and sex
In general, the outcome following SICH is poor with advancing age. The SICH score for prognostication has 80 years as a deciding cutoff.[29] The meta-analysis of 14 trials by Gregson et al. observed that 85% of patients aged 70 or above had an unfavorable outcome compared with 75% of those aged 50–69 and 68% of patients aged under 50.[26] Sex has not been independently analyzed in most series except Maila, who male sex and an age below 60 years to be good prognostic indicators following surgery.[28] The mean age of presentation of SICH in most of the Indian series including ours has been around 55–60 years. Thus, from an Indian perspective, it would be reasonable to keep 60 years to be an optimal cutoff favoring surgery.
Neurological grade on presentation
GCS is an independent predictor for outcome following SICH, lower the GCS, poorer the outcome.[29],[30] GCS; however, often does not correlate with the size of the clot and one may have a low GCS in a patient with a small clot. A small clot is not an indication for surgery, however, poor the GCS be. Almost all individual studies and trials to date have shown that the group of patients with a GCS between 9 and 12 demonstrated a significantly improved outcome with surgery (OR 0.54; 95% CI 0.37, 0.77) (P = 0.0009).[26],[29],[30]
Volume of the clot
Different surgical series have used varying criteria and the distinction between small, moderate, and large clot is unclear. In general, a clot of volume above 30 ml indicates a probable role for surgery and clot size above 70 ml predicts a fatal outcome.[29] Gregson’s meta-analysis revealed that the only category showing a significant treatment effect was the group with the volume of between 20 and 49 ml.[26] Few recent studies, especially those proposing decompressive craniectomies (DC) have found better outcomes even with clots as large as 70 ml.[31] It is reasonable to assume that surgery may be considered if the clot size is above 20 ml and to defer surgery if the clot size is above 70 ml in view of probable fatal outcome.
Site of hematoma
The controversy regarding surgery for SICH essentially pertains to deep-seated gangliocapsular hematomas. Primary SICHs at other sites are relatively less controversial. Brain stem hematomas carry a poor prognosis and are best left alone. Hemorrhage involving the cerebellum can be associated with acute hydrocephalus and rapid neurological deterioration. Several large studies have shown that DC with clot evacuation with external ventricular drain (EVD) insertion provides good outcome, especially in patients with a clot size above 3 cm and sometimes even in comatose patients with preserved brainstem reflexes. Insertion of EVD alone is not recommended except as an emergency measure before surgery because of the theoretical risk of upward herniation.[1] Patients with cerebellar hematomas having a GCS score of 14–15 and small hematomas (≤3 cm) are best treated conservatively.[1],[32],[33],[34],[35]
Lobar hematomas may often have underlying vascular malformation which can confound the decision-making process. Several studies including STICH I have observed a favorable outcome with surgery for lobar hematomas without intraventricular extension, especially in young patients with deteriorating sensorium.[1],[7],[8],[16],[18]
Timing for surgery?
More than half the deaths following SICH occur within 48 h of hemorrhage.[28] Clot expansion due to rebleeding occurs maximally within 3–4 h but may happen up to 24 h.[28] Early surgery thus appears to be justified, but the timing of the surgery for ICH is controversial. The benefit of early surgery (within 12 h) in ICH was first observed by Morgenstern et al. in 1998 and later reconfirmed by STICH II (within 21 h) results.[8],[14] An individual patient meta-analysis of 2186 patients from 8 trials of surgery for ICH found that surgery improved outcome if performed within 8 h of hemorrhage.[22],[36] However, ultra-early craniotomy (within 4 h from ictus) on the other hand was found to be associated with an increased risk of rebleeding.[37] On the basis of these observations, it is reasonable to suggest surgery at the earliest but not earlier than 4 h.[36]
Spot sign
Hematoma expansion has been identified as one of the most important determinants of early neurological deterioration and poor outcome in primary ICH. Spot sign described as the presence of active contrast extravasations into the hematoma at the time of computed tomography angiography (CTA) is an indicator of active hemorrhage and hematoma expansion. Kim et al. observed that surgical treatment of supratentorial ICH in patients with spot sign positive in CTA was associated with less mortality despite of long duration of in-hospital stay.[38] However, they failed to show that any statistically significant of surgical treatment over conservative treatment in patients with positive spot sign.
Choice of surgical procedure
Surgical interventions in SICH are of different types. The standard surgical procedure adopted in primary ICH is a small craniotomy, corticectomy, and hematoma evacuation. Minimally invasive techniques such as endoscopic hematoma evacuation and stereotactic hematoma evacuation are gradually replacing the conventional craniotomy techniques.[16],[39],[40],[41],[42] DC with or without duroplasty and clot evacuation is another option employed, especially for large hematomas.[43],[44],[45],[46],[47] Burrhole and EVD of acute hydrocephalus, fibrinolysis of IVH using recombinant tissue plasminogen activator (rtPA), or streptokinase are other indications for surgery, especially in IVH. The current recommendations of the AHA also advocate the use of ICP monitoring in all patients with a GCS score of ≤8, those with clinical evidence of transtentorial herniation, or those with significant IVH or hydrocephalus (Class IIb; Level of Evidence C).[1]
Minimally invasive surgery
These include stereotactic aspiration of clot with thrombolysis and endoscopic clot evacuation through burr holes. Overall, minimally invasive surgery (MIS) has reported better clot removal rates compared with standard surgical techniques.[16],[39],[40],[41],[42] Cho et al. and a few recent meta-analysis comparing three approaches (neuroendoscopy vs. stereotactic aspiration vs. craniotomy) and observed better functional outcomes within 6 months in endoscopically operated patients.[39] Results from “Minimally Invasive Surgery Thrombolysis Plus Recombinant Tissue-type Plasminogen Activator for ICH Evacuation” (MISTIE) and results from “Stereotactic treatment of intracerebral hematoma by means of plasminogen activator” showed greater clot resolution and decreased perihematomal edema with MIS and rtPA than with traditional medical management.[16],[41] A meta-analysis by Zhou et al. of 12 RCTs with 1955 patients suggest that MIS is superior to conventional technique, especially in patients of age between 30 and 80, those with superficial hematoma, GCS score ≥9, hematoma volume between 25 and 40 ml, and if intervention performed within 72 h after onset of symptoms.[39] Although trials such as MISTIE I and II have shown to reduce surgical trauma, provide better clot removal, and an overall trend toward better outcome, results from further trials such as MISTIE III is required to validate them and at present the effectiveness of minimally invasive clot evacuation with stereotactic or endoscopic aspiration with or without thrombolytic usage is uncertain (Class IIb; Level of Evidence B).
Decompressive craniectomy
The usual operative intervention in large hypertensive ICH has been craniotomy and evacuation of the hematoma without doing a DC. Adding DC and expansile duroplasty (ED) to ICH evacuation could accommodate the mass effect emanating from delayed brain edema, residual hematoma, and/or rebleeding. A systematic review of studies, in which DC was performed in patients with SICH observed that DC with hematoma evacuation might be safe and might improve outcomes.[43],[44],[45],[46],[47] Li et al. found a benefit of adding DC and ED to ICH evacuation in younger age groups, poor grade patients (GCS <6), clot volume >50 mL, ICH score >3, presence of IVH and in patients with refractory ICP. Li et al. have also proposed that DC with ED need to be done in all patients with malignant brain swelling, absent or faint brain pulsation, and intraoperative ICP >20 mmHg.[31] There is sufficient literature evidence to suggest that DC with ED might reduce mortality for patients with supratentorial ICH who are in a coma, have large hematomas with significant midline shift, or have elevated ICP refractory to medical management (Class IIb; Level of Evidence C).[1]
Intraventricular hemorrhage
IVH may be primary without any associated parenchymal bleed or may be secondary to seepage, especially from large thalamic or basal ganglia hematomas. It has been reported being present among 40% to 60% of all ICH patients and is considered a poor prognosticator for outcome. Blood in the ventricle may cause acute hydrocephalus due to obstruction of cerebrospinal fluid (CSF) pathway or may cause delayed hydrocephalus due to inflammatory scarring from the degradation products.
In acute hydrocephalus, an EVD is required to drain CSF but carries a risk of frequent blockage due to the blood clots. Intrathecal thrombolysis with urokinase or streptokinase helps to dissolve the clots and reduce the risk of hydrocephalus. Several trials have studied the efficacy of Intraventricular fibrinolysis and found it to be safe, useful in reducing mortality, and improving functional outcome without increasing the risk of infection or rebleeding.[48],[49],[50],[51],[52],[53],[54] The Clot Lysis: Evaluating Accelerated Resolution of IVH III studies have shown that the use of alteplase was associated with a faster rate of clearance of IVH and 10% reduction in mortality in the whole population (P <.007).[53] Yet, another option is the use of neuroendoscopic to remove the blood clot in IVH.[54] Although clear-cut guidelines are yet to be evolved, it can be safely concluded that the ventricular drainage without thrombolysis and endoscopic evacuation of an IVH is the future modalities for treatment for IVH, especially in patients with decreased level of consciousness (Class IIa; Level of Evidence B).[1],[40]
Conclusion |
Indications for surgery in SICH are still unclear, but there certainly seems to be reversal in trend toward a more aggressive surgical approach using minimally invasive techniques. Small clots (<20 ml), brain stem hematomas, elderly patients (above 70 years), and poor grade patients (GCS < 8) are best managed conservatively. Patients in good grade (GCS 14–15) should be considered for surgery only if a trial of conservative management fails. Mortality in patients with moderate to large hematomas can be reduced by surgical evacuation of the clot alone or combined with DC and ED. IVHs dissolve faster through thrombolysis through an EVD or by endoscopic evacuation. Cerebellar hematomas more than 3 cm with mass effect and lobar hematomas with neurological deterioration should undergo surgical removal. The future of surgery in SICH may lie in the use of minimally invasive neurosurgical techniques for clot evacuation.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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