Original articles

Outcome of aneurysmal subarachnoid patients 66 years of age and older

hemorrhage in

J. Paul Muizelaar, Marinus Vermeulen, Hans van Crevel, Albert Hijdra, Jan van Gijn, Graham M. Teasdale, Ken W. Lindsay, and Gordon D. Murray

Introduction

Subarachnoid hemorrhage (SAH) in the elderly becomes an increasingly more important prob- lem. Not only do more and more people live to their seventh and eighth decades, but the in- cidence of SAH also rises rather sharply with advanced age. In Phillips’ et al. study in the population of Rochester, the incidence of aneu- rysmal SAH increased from 2.5/l~,~/year in the 25-34 year age group, through 2O/lOO,~O/year in the 45-54 year age group to 40/100,OOO/year in the 75+ year group]. Al- though considerable variation in the manage- ment of patients with SAH in the younger age groups exists, this seems to be even more the case in the older age group2.3.

Most believe that the prognosis following sub- arachnoid hemorrhage in the elderly is poor, yet papers specifically dealing with cerebral aneu- rysms in older patients describe good results in surgical series4-‘*. These workers conclude that advanced age per se is no contraindication for intracranial surgery. In those series case selec- tion and ‘center’ selection probably exist; a neu- rosurgical center with poor results will less likely report on those cases. In fact, in only one paper poor outcome led the authors to suggest that limited resources for diagnostic investigations, such as angiography, or highly specialized care

Summary

The outcome at three months after aneurysmal SAH in a group of older patients and a group of younger patients is compared. The patients were admitted within 72 hours of their SAH. Of 61 patients 66 years of age and older, com- prising 13% of the whole patient group, 52% died, 12% remained dependent and 36% be- came independent. In the younger group, 55% had an independent outcome (p < 0.01). In contrast to what we expected in the older pa- tient group, not extracranial, but intracranial events (re-bleeds, infarcts, hydrocephalus) were by far the most frequent cause of deterio- ration.

Key words: Subarachnoid hemorrhage, aneu- rysm, elderly patients. 1

in a neurosurgical unit not be wasted on these patients . ” EpidemioIogic studies provide data on the natural history or conse~ative manage- ment of subarachnoid hemorrhage in the elder- l~‘~,‘? Indeed, these patients fare worse than the younger ones in those studies; however, the rea- sons remain unclear.

The purpose of this paper is to analyze the factors leading to a specific outcome in a group of mainly conservatively managed older pa- tients and to compare them to a group of young- er patients.

From the Division of ~eurasurgery, Medical College of Virginia, Virginia CommonweuI~h University, Richmond, Virginia; the Departments of Neurology, University Hospital (Dijkzigt), Rotterdam; Academisch Medisch Centrum, University of Amsterdam, Amsterdam; University Hospital, Utrecht, the Netherlands; and the Departments of Neurosurgery, University of Glasgow, Glasgow, Scotland, and the Royal Free Hospital, London, England.

Address for correspondence and reprint requests to: 1. Paul Muizelaar, Division of Neurosurgery, Box 631, MCV Station Richmond, VA 23298-0001 USA.

Accepted22.10.87

C&n Neural Neurosurg 1988. Vol.90-3. 203

Clinical material and methods

The study group consisted of 61 patients of 66 years of age and older. There were 16 males and 45 females. All patients formed part of a double- blind, randomized, placebo-controlled study on the effectiveness of an anti-fibrinolytic agent (tranexamic acid, Cyklokapron@), conducted between November 1977 and January 1983 in four hospitals in Great Britain and the Nether- lands14. All patients received the first dose of tranexamic acid within 72 hours from the first SAH14. The dosage was 6 x 1 g i.v. in the first week and 4 x 1 g i.v. in the second, followed in the next two weeks by 4 x 1 g i.v. (The Nether- lands) or 4 x 1.5 g p.o. (Great Britain). We placed particular reliance on CT scans; a CT scan was obtained every week and with each deterioration15. All data were gathered prospec- tively and computerized, as described before14. The mean age of the group over 65 years was 71.9 f 5.6 years (range 66-87 years), that of the younger group was 47.3 (range 18-65) years. There were 35 patients 66-70 years of age, and 26 patients 71 years and older. We found no difference between these two subgroups and, therefore, considered these as a single group. Of the 61 patients, 42 were admitted to the neurol- ogy service and only 19 to neurosurgery. The total number of patients in the tranexamic acid study was 479. The 61 elderly patients thus com- prised 12.7% of the whole series. On the neurol- ogy service, without any patient selection as to age or grade, they represent 20% of the study population (42 of 210 patients).

An aneurysm was demonstrated in all 16 pa- tients undergoing autopsy. Angiography re- vealed an aneurysm in 12 of 13 patients. In two patients both angiography and autopsy were performed. Thus, investigations demonstrated an aneurysm in 26 out of the 27 patients; one each in the basilar artery, posterior inferior cer- ebellar artery, internal carotid artery and oph- thalmic artery, 4 in the middle cerebral artery, 11 in the anterior communicating artery, and 7 in the posterior communicating artery. In this older group an aneurysm was demonstrated in 43% (26 of 61), in the younger group this amounted to 72% (302 of 418). In the other patients, the diagnosis of ruptured aneurysm was based only on CT scans, relying in particular

on the presence of blood in the basal cisterns”’ Only three patients (5% j underwent aneurysm clipping, all with good result, the others were not considered as suitable candidates for sur- gery because of their age, clinical condition, or site of their aneurysm. In the group of younger patients, 187 (45%) underwent operation.

The five-point Glasgow outcome scale” was reduced to three outcomes - death; persistent vegetative state/severe disability (dependent state); and moderate disability/good recovery (independent state).

Results

Table 1 shows the patient outcome at three months related to the modified (no correction for age or hypertension) Hunt and Hess score’” and 1Cpoint Glasgow Coma Scale” on admis- sion. It appears that in this patient group, the neurological condition on admission has only a weak correlation with outcome; even 3 of 13 (23%) patients admitted in grade IV reached an independent outcome. On the other hand, 15 of the 29 patients (52%) who were admitted in grade I or II died, 10 of them from re-bleeding.

Table 2 shows a comparison of the patients 66 years and of those aged 65 years and less with outcome categorized for each study-arm. Mor- tality is considerably higher in the group of el- derly patients, and independent outcome is only two-thirds as frequent in this group (36%) as in the younger group (55%) (chi-square = 7.88 1 d.f., p < 0.01).

Table 3 shows the causes of death in the two groups of patients. Although we did not find an effect upon outcome in the original study, the drug certainly changed the cause of death14. The results do not differ in the elderly patients. Of all the deaths, re-bleeds caused only 21% in the drug group and 62% in the placebo group (chi- square = 5.40 1 d.f., p = 0.05). Three re-bleeds in the placebo group occurred between 4 and 12 weeks post-SAH. Cerebral infarcts, on the oth- er hand, were four times as frequent as a cause of death in the drug group. In the elderly tranex- amic acid group there was a high frequency of hydrocephalus. In these cases, deterioration in the patients’ condition was ascribed to hydro- cephalus only after repeated CT scanning when

204

Table 1. Outcome at Three Months Reiated to Modified Hunt and Hess Score and to Glasgow Coma Score at Admission (n = Number of Patients)

Modified Hunt and Hess Score at Admission

1 2 3 4 5

-.. ---__ Glasgow Coma Score at Admission

Outcome -~_

Independent Dependent Dead Total n n n n

5 66 < 66 2 66 < 66 2 66 < 66 2 66 < 66 _..___.~

4 53 0 5 2 15 6 73 9 99 1 14 13 44 23 157 6 67 4 14 9 32 19 113 3 12 2 13 8 44 13 69 0 0 0 0 0 6 0 6

.--

--~-_~_ _- -.-- 14 14 144 1 21 14 56 29 221 12 or 13 4 68 3 13 10 35 17 116 < 12 4 19 3 12 8 50 15 81

_..- -.-__ Total 22 231 7 46 32 141 61 418

Table 2. Outcome at Three Months*

Tranexemic Acid Placebo Total _

Total 37 24 Dead 19 (51%) 13 (54%) f:. (52%) Patients 66+ Dependent 6 (16% 1(4%) 7 (11%)

Independent 12 (32%) 10 (42%) 22 (36%) --______._ ~~ ~____ ...-l-._._.--

Total 204 214 418 Dead 65 (32%) 76 (36%) 141 (34%)

Patients 65- Dependent 24 (12%) 22 (10%) 46(11%) Independent 115 (56%) 116 (54%) 231 (55%)

* All but three patients 66+ years were managed conservatively.

Table 3. Causes of Death* *

Tranexemic Acid Placebo Total -._-

Patients 66+

Total Re-bleed Infarct Hydrocephalus* Others+

.-- ~____ _~_ ~_ .._ ._ ._ 19 13 32 4 (21%) 8 (62%) 12 (38%) 6 (32% 1(8%) 7 (22%) 4 (21%) 1(8%) 5 (16%) S (26%) 3 (23%) 8 (25%)

_.___~ -.__ -. ..___.- Total 65 76 141 Re-bleed 15 (23%) 37 (49%) 52 (37%)

Patients 65- Infarct 32 (49%) 23 (30%) 55 (39%) Hydrocephalus 0 0 0 Others 18 (28%) 16 (21%) 34 (24%)

* * All patients 66+ were managed conservatively. *These patients died with hydrocephalus, see text. + One of these patients died from his first hemorrhage. The other patients died from extracranial complications.

7

205

other causes for deterioration were excluded. Although we do not believe that hydrocephalus yer se caused the death of these patients, it may have triggered a chain of intracranial and extra- cranial events leading to the patient’s final de- mise20. We have therefore maintained hydro- cephalus as a separate cause of death in Table 3. Acute hydrocephalus preceding a fatal infarc- tion was discussed by us in a separate paper”‘, and in these cases infarction was listed as the cause of death.

Only 7 out of the 32 dead patients (22%) (11% of the whole group) died from extracra- nial causes: two from gastrointestinal bleeding and one each from sepsis and an unclear cause in the drug group, and one each from pulmonary embolus, pneumonia and mediastinal hermor- rhage from an unknow source in the placebo group.

There is, in this study, not a clear single rea- son why the elderly did iess well. than the young- er patients. Fatal re-bleeds occurred in 20% and 13%) respectively. Other fatal intracranial events occurred in 20% and 13%) respectively, and fatal extracranial events in 12% and 8%, respectively.

Discussion

Although this study comprises only 59 patients, it is, to our knowledge, the only prospective study specifically dealing with the outcome and causes for deterioration in the elderIy patient with SAH. Moreover, a conscious effort was made to avoid the many pitfalls in establishing the cause of deterioration in SAH patientP’, by relying in particular on CT scans. This paper shows that the outcome after SAW: in the elderly patient is, indeed, much worse than that in his younger counterpart. Good and moderately dis- abled (independent) outcome occurs one and a half times more often in patients less than 66 years old than in those 66 years and older (if the patient lives to be admitted to a hospital within 72 hours of his first SAH). However, after 3 months one third (18 of 55 patients) of the older, mainly conservatively managed patient group had reached an independent state.

In comparing the causes of death, we find that intracrania1 secondary events were as common in the group of older patients as in the younger

patients, The rubric ‘others’ in ‘I’able 3 repre- sents 27% of the causes of death in the elderly, This is equivalent to the 24% ‘others’ in the younger patients and, even taking into account that the death rate is higher in the elderly, it shows that the older patients do not all die from pneumonia, cardiac failure, or other complica- tions not directly related to the ruptured aneu- rysm.

The earlier study in the whole patient group showed that tranexamic acid has no significant effect upon outcome “, Applying strict criteria to ensure that Type II errors (false-negative re- sults) do not occur prevents conclusions about the apparent lack of drug effect on outcome in the elderly group. Even the differences between the drug and placebo groups concerning the causes of death in the elderly are not statistically significant. However, the figures for the elderly correspond so well with those from the entire group in our previous studyiJ, or with those from the study on the effects of antifibrinolytic agents reported by the International Cooperative Study on the Timing of Aneursym Surgery2”. suggesting that the conclusions from those stud- ies are also valid for the elderly patients. Thus, in this group too, it appears that the antifibrino- lytic agent did work (reduction of re-bleeding), but did not benefit patient outcome.

In the group of older patients. re-bleeding was the singie most frequent cause of death, despite the likely preventitive effect of antifibri- nolytics and the fact that in this group a larger proportion of the patients were randomized to the drug group (61%) than to the placebo (39%). Witholding antifibrinolytics, which do not improve outcome, would undoubtedly lead to a further increase in the number of re-bleeds.

Only clipping of the aneurysm definitively prevents re-bieeding. Hogusson noted in 1973 that patients between 60 en 70 yeas with an aneurysm can be operated upon with gratifying results’. Amacher et al. compared 373 patients below the age of 60 and 88 patients above this age, all with anterior circulation aneurysms, and concluded that the risks of surgery itself are practically the same for both age groups4,“. The reduced life expectancy of the elderly patient, may deter many surgeons from direct aneurysm repair, but this may be underestimated; in The Netherlands the mean life expectancy of an

206

80-year-old female is another 8.2 years’“. Whether surgery in older, unselected patients can improve outcome, requires further study.

References

PHlLLlPSLH,WHISNANTJP,O'FALLONWM,SUNDTTM.Th~

unchanging pattern of subarachnoid hemorrhage in a community. Neurology 1980; 30:1034-40. DRAKE co. Viewpoint: Senior citizen with ruptured aneu- rysm. Neurosurgery 1980; 6605-6. SLOSBERG PS. Viewpoint: Senior citizen with ruptured aneurysm. Neurosurgery 1980; 6605-6. AMACHER AL. Letter to the editor. Neurosurgery 1980; 6:612. AMACHER AL, FERGUSON CC, DRAKE CG, GIRVIN IP, BARR

HWK. How old tolerate intracranial surgery for aneu- rysms. Neurosurgery 1977;1:242-4. FEIN JM. Aneu~sms in geriatric patients, in HOPKINS LN, LONG DM, eds. Clinical Management of Intracranial Aneurysms. New York: Raven Press, 1982: 183-91. HOGUSSON R. Intracranial arterial aneurysms: Consid- erations on the upper age limit for surgical treatment. Acta Neurochir (Wien) 1973; 28:157-r%. SENGUPTAR~,LA~~MANL~,HANKINSONJ. Scopeofsurgery for intracranial aneurysms in the elderfy: A pre~minary report. Br Med J 1978; 2:246-7. SHEPHARD RH. Subarachnoid hemorrhage in patients over 59. Br Med J 1978; 1:921, (Letter). SHEPHARD RH. Age and the outcome from aneurysm surgery. J Neurosurg 1984; 60:215-216, (Letter). MARTINDALE BV, GARFIELD J. Subarachnoid hemorrhage above the age of 59: Are intracranial investigations justi- fied? Br Med J 1978; 1:465-6. KELLER AZ. Hypertension, age and residence in the sur- vival with subarachnoid hemorrhage. Am J Epidemiol 1970; 91:139-47.

PAKARINEN s. Incidence, etiology and prognosis of pri- mary subarachnoid hemorrhage. Acta Neural Stand (Suppl) 1967; 29:1-128. VERMEULENM,LlNDSAYKW,MURRAYGD,CHEAHF,HlJDRA

A,MUlZELAARJP,SCHANNONGM, TEASDALEGM,VANCRE-

VEL H, VAN GUN J. Antifib~nolytic treatment in subarach- noid hemorrhage. A multicenter double-blind, placebo- controlled trial. N Eng J Med 1984; 311:432-7. VERMEULEN M,VAN GllNJ,HlJDRAA,CREVELH.CBUSeSOf

acute deterioration in patients with a ruptured intracra- nial aneurysm. A prospective study with serial CT scan- ning. J Neurosurg 1984; 935-9. VAN GIJN J, VAN DONGEN KJ. Computerized tomography in subarachnoid hemorrhage: difference between pa- tients with and without an aneurysm on angiography. Neurology 1980; 30538-9. JENNET B, BOND M. Assessment of outcome after severe brain damage: a practical scale. Lancet 1975, 1:480-4. HUNT WE, HESS RM. Surgical risk as related to time of intervention in the repair of intracranial aneurysms. 3 Neurosurg 1968; 28: 14-20. TEASDALE G, JENNET B. Assessment of coma and impaired consciousness: A practical scale. Lancet 1974; 2:81-4. VAN GUN J,HIJDRA A, WIIDICKS EFM,VERMEULEN M,VAN

CREVEL H. Acute hydrocephalus after aneurysmal sub- arachnoid hemorrhage. J Neurosurg 1985; 63:355-62. VAN CREVEL H. Pitfalls in the diagnosis of re-bleeding from intracranial aneurysms. Chn Neurol Neurosurg 1980; 82:1-9. KASSELL NF,TORNERJC,ADAMS HP. Antifibrinolyticther- apy in the acute period following aneurysmal subarach- noid hemorrhage. Preliminary observations from the cooperative aneurysm study. J Neurosurg 1984; 61:225-30. Vademecum Gezondheids statistiek Nederland 1984. Centraal Bureau voor de StatistieWMinisterie van Volksgezondheid en Milieuhygiene. The Hague: Staats- uitgeverij, 1984: 143.