Surgical Evacuation

The first randomized trial assessing the value of surgical evacuation in patients with ICH was conducted by McKissock et al. in 1961 (1), before CT technology became available, an important limitation that implies that misdiagnosis at the time of enrollmentlikely resulted in the inclusion of patients without ICH. Actually, the authors recognized several misdiagnosed cases after randomization, reaching a known diagnostic error of 5%. The investigators randomized 180 patients to surgical evacuation (if the hematoma could be localized and was surgically accessible) or to conservative management. The results showed that patients in the surgical group had a 28% increased mortality rate and worse overall functional outcome. The odds ratio (OR) for death or dependency was 2.0, with a 95% confidence interval (CI) of 1.04 to 3.86.

Another study randomized 52 patients with ICH to surgery or medical treatment within 48 hr of symptom onset (2). Upon enrollment, patients were unconscious (but responsive to pain) or had severe hemiparesis or aphasia. Randomization was not well balanced because patients allocated to surgical treatment had larger hematomas and significantly lower Glasgow Coma Scale (GCS) at entry. Both mortality and functional dependence were slightly higher among surgically treated patients. A small number of patients enrolled precluded subgroup analysis. The authors logically concluded that spontaneous ICH should be treated conservatively.

Enrollment in a third trial was interrupted after only 21 patients had been randomized (3). The therapeutic arms were best medical treatment (including routine use of steroids and mannitol), best medical treatment plus ventriculostomy for intracranial pressure monitoring, and surgical evacuation (with attempts to standardize the procedure using a predefined microsurgical technique). The trial was prematurely terminated because of the extremely poor outcome observed in both treatment groups. No differences among the groups were noticed, but the very small number of patients studied impeded any meaningful comparison.

In the only randomized trial that solely used endoscopic aspiration for clot evacuation, favorable results were reported with surgery (4). The investigators randomized 100 patients with symptomatic hematomas > 10 cc within 48 hr of symptom onset to partial endoscopic evacuation through a burr hole or medical treatment (including antifibrinolytic agents for 3 days). At 6 months, mortality was significantly lower, and functional outcome was improved in the surgically treated patients. Subgroup analysis showed that the benefit afforded by surgery was restricted to patients younger than 60 years old who presented with lobar hematomas and were not stuporous at entry. The results of this trial have been questioned because outcome assessment was not blinded. However, this study remains the strongest evidence in favor of surgical treatment for spontaneous ICH.

The concept of early surgery has been tested in a few small, randomized studies. One randomized 20 patients (over a 2-year period) with ICH volume > 10 cc, focal neurologic deficit, and GCS > 4 at the time of enrollment to either surgical evacuation (craniotomy or stereotactic aspiration as decided by the case surgeon) or medical treatment (5). All patients were enrolled within 24 hr of symptom onset and underwent surgery within 3 hr of randomization. Median time from onset of symptoms to surgery was 8 hr and 35 min. Patients' neurologic status at the time of randomization was better than in previous trials; median GCS was 13 (range, 11-14) in the surgical arm and 11 (range, 6-13) in the medical arm (p = 0.06). At 3 months, a nonsignificant but well-defined trend toward better outcome in the surgically treated patients was apparent on 3 different functional scales. Mortality was only minimally lower in the surgical group, but surgery afforded a significant reduction in residual neurologic deficits, as assessed by the National Institutes of Health stroke scale.

Although intuitively appealing, early surgery to prevent the consequences from hematoma expansion has been formally evaluated with disappointing results. First, a single-center, pilot trial compared craniotomy within 12 hr of symptom onset versus best medical treatment (6). Inclusion criteria required hematoma volume > 10 cc and presence of impairment of consciousness or severe hemiparesis. A total of 34 patients were randomized, and at 6 months, a trend toward lower mortality and better functional outcome was observed in the surgical group, although it is unclear if outcome assessment was blinded. Albeit modest, the benefits observed with early surgery in this pilot study reasonably led the investigators to postulate that shortening the time window to surgery could maximize the benefit of the intervention. Thus, a subsequent trial enrolled patients for craniotomy and clot evacuation within 4 hr of symptom onset to compare them with the patients who had been randomized to the surgical and medical treatment arms within a 12-hr time window in the previous study (7). Median initial hematoma volume was 40 cc (range, 23-84 cc), and median GCS was 12 (range, 6-15). The trial was prematurely terminated after only 11 patients had undergone surgery within 4 hr because of increased rate of rebleeding (40% compared with 12% among patients who underwent surgery between 4 and 12 hr) and mortality (36% vs. 18% in patients who went to surgery between 4 and 12 hr, including 3 of 4 patients who rebled). The investigators concluded that ultraearly craniotomy for hematoma evacuation cannot be recommended because it is complicated by rebleeding, most likely related to problems with homeostasis.

Several meta-analyses have attempted to systematically review the data of these prospective randomized studies (8-13). The results should be interpreted with caution because of the marked heterogeneity of the original trials, which varied considerably in terms of diagnostic and inclusion criteria, surgical technique, outcome measures, and size of the population studied.

Older meta-analyses (8-10), including the first 4 randomized trials (1-4), concluded that craniotomy showed a tendency to be detrimental. Pooled data from these trials (n=349 patients) shows a nonsignificant increase in the odds of death and dependency at 6 months for surgical patients (OR: 1.23; 95% CI: 0.77-1.98). A subsequent meta-analysis (13) included the two more recent trials (5,6) as well as another previously overlooked Chinese study (14). When all trials (n=530 patients) were considered, the trend was still toward greater chance of death and dependency among patients undergoing surgery (OR: 1.20; 95% CI: 0.83-1.74). However, when the 2 trials with the most notable methodologic weaknesses were excluded, the results changed sensibly. The oldest study (1) was excluded because of the high diagnostic error rate as a result of the unavailability of CT at the time of the study and the uncertainty about the number of patients allocated to surgery who actually underwent craniotomy. The Chinese study (14) was removed due to concerns about poorly balanced randomization, inclusion of cerebellar hematomas, and possible incorporation into the surgical group of patients who only underwent ventricular drainage. After these exclusions, the resulting meta-analysis (n=224) actually indicated a trend toward a reduction in the odds of death and dependency after surgery (OR: 0.63; 95% CI: 0.35-1.14).

These meta-analyses do not include the most recent trials. A randomized, multicenter trial compared stereotactic blood clot drainage after liquefaction with urokinase (instilled through a catheter into the hematoma every 6 hr for 2 days) with conservative treatment (15). Seventy patients were enrolled within 72 hr of ICH onset. No differences in mortality or severe disability between the treatment groups were observed. However, a significant ICH volume reduction was achieved by neurosurgical intervention (10-20%; p < 0.05).

By far, the largest randomized trial evaluating surgical evacuation in the management of ICH, the International Surgical Trial in Intracerebral Hemorrhage was an international (27 countries), multicenter (83 centers) study that enrolled 1033 patients to receive early surgery or initial conservative treatment. Eligible patients had confirmed spontaneous supratentorial ICH that had arisen within the previous 72 hr, with a minimum hematoma diameter of 2 cm and GCS > 4. Patients randomized to the surgical arm underwent hematoma evacuation within the following 24 hr. The trial protocol did not include a standardized surgical technique; thus, the responsible surgeon chose the method used for evacuation in each case. Best medical treatment was similarly left to the discretion of the participating clinicians. Later surgical evacuation was allowed in patients initially treated conservatively, if it was deemed necessary due to neurologic deterioration. Outcome measures were death and functional disability at 6 months, as measured by several validated functional scales and using information obtained through structured postal questionnaires. The investigators adopted a pragmatic prognosis-based outcome to evaluate functional end results; patient outcomes were categorized as good or poor upon randomization, and this classification was considered to establish different outcome expectations. Analysis of results was based on intention-to-treat.

In total, 503 patients were randomized to early surgery and 530 to conservative treatment. Groups were well balanced for meaningful baseline variables. Median age was 62 years, and more than half of all patients were randomized within 20 hr of hematoma onset. Twenty percent of patients were comatose (GCS 5-8) upon enrollment. Hematomas were fairly equally distributed between lobar and ganglionic locations in both treatment groups. Median hematoma volume was 38 mL and comparable in both groups. Ninety-four percent of patients randomized to early surgery actually underwent evacuation. Median time between ictus and surgery was 30 hr, and between randomization and surgery, 5 hr. Meanwhile, 26% of patients randomized to initial conservative treatment eventually went to surgery due to neurologic deterioration after a median interval from ictus of 60 hr. Craniotomy was the procedure chosen for evacuation in 77% of surgical patients.

After excluding patients lost to follow-up or with insufficient follow-up information, the final population analyzed consisted of 468 patients randomized to the surgical arm and 497 patients randomized to the conservative arm. Favorable functional outcome using the extended GCS occurred in 26% of patients who were randomized to early surgery and 24% of those randomized to initial conservative treatment (OR: 0.89; CI: 0.66-1.19; p=0.41). Therefore, early surgery resulted in a nonsignificant absolute benefit of 2.3% and a relative benefit of 10%. Similar results were observed with other functional scales. Mortality rates at 6 months did not differ much between treatment groups (36% vs. 37% for early surgery and initial conservative approach, respectively).

On subgroup analysis, the only remarkable finding was the greater likelihood of favorable outcome with early surgery among patients with superficial hematomas (i.e., located 1 cm or less from the cortical surface). For these patients, early surgery afforded an absolute benefit of 8% over initial medical treatment (p=0.02). Conversely, patients with deep hematomas tended to fare better with conservative treatment. Craniotomy appeared to offer an advantage over other surgical techniques, but the difference was not significant, and the number of patients treated with methods other than conventional craniotomy might have been too small to draw reliable conclusions. In the subpopulation of comatose patients, early surgery was actually associated with a trend toward increased risk of death or disability.

In conclusion, surgical evacuation cannot be advocated as standard treatment of choice for most patients with acute primary ICH. The role of surgery should probably be restricted to patients deteriorating because of mass effect. Nonetheless, future studies may define a particular niche for specific surgical interventions targeted to well-defined subpopulations of patients.

The most important features of the randomized trials on surgical versus medical treatment of ICH are summarized in Table 1.

Table 1 Summary of Published Randomized Trials Comparing Surgical and Medical Treatment for Patients with ICH
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