J Neurosurg47:761-765, 1977

The management of ruptured intracranial aneurysm in sickle cell anemia Case report


Department of Neurosurgery, Temple University Hospital, Philadelphia, Pennsylvania

The problem of sickle cell disease and its complications is discussed. Subarachnoid hemorrhage is not a common complication of sickle cell disease and should be evaluated in the same way as if it were not associated with the disease. Patients with sickle cell trait have an added risk during angiography and hypotensive anesthesia. Guidelines are given for angiography and craniotomy with hypotensive anesthesia and reduction of brain volume in these patients. KEY W o n v s 9 sickle cell disease 9 sickle cell trait subarachnoid hemorrhage 9 aneurysm


UBARACHNOIDhemorrhage is not a common complication of sickle cell disease. When it occurs, it should be evaluated and treated in the standard fashion; that is, with four-vessel angiography and the appropriate surgery. A review is given of sickle cell disease, a case is presented, and criteria are listed whereby angiography and major surgery can be safely accomplished in persons with sickle cell disease. Clinical Background

Sickle cell anemia is a chronic hereditary, hemolytic disease, the result of the inheritance from each parent of a gene for hemoglobin S. The resulting red corpuscle is a homozygote (hemoglobin SS), which is lacking in hemoglobin A, and when deprived of oxygen, assumes sickle and other bizarre shapesY Sickle cell anemia occurs in one of every 625 births among Negroes in the United States. '6 J. Neurosurg. / Volume 47 / November, 1977


On the other hand, sickle cell trait is the result of heterozygosity for hemoglobin S, usually in the form of hemoglobin SA. This is the asymptomatic or carrier state, and occurs in 8% of Negroes in the United States. 46 The common sickling states are: a~ 1. Hemoglobin SS or sickle cell disease 2. Hemoglobin SA or sickle cell trait 3. Hemoglobin SC or sickle cell C disease 4. Hemoglobin SBT or sickle cell B Thalassemia. For purposes of discussion, only the more common types, SS and SA will be considered. Although sickle cell disease was first described by Herrick in 1910,20 it was introduced as a definite clinical entity with neurological manifestations in 1923 by Sydenstricked, et aL, 42 and later defined as a molecular disease by Pauling, et aL s' Sickle cell disease is characterized by chronic hemolytic anemia, hyperbilirubinemia, recurrent painful crises, multiple 761

R. A. Close and W. A. Buchheit organ infarctions, and usually shortened life span. a2,'7 In general, 18% of patients with sickle cell disease have neurological complications? ~,38 The lesions in the central nervous system are primarily due to intravascular occlusion21,4~ with resultant infarction and necrosis. 4,1e,21,38,41,45 Although other types of central nervous system complications can occur in sickle cell disease, 1,2,5,9,s~,45 only cerebral infarction can be clearly attributed to the abnormal hemoglobin (SS). Subarachnoid hemorrhage, seizures, signs of meningeal irritation, and radicular syndromes should not be attributed to sickle cell disease without appropriate investigation to exclude other causes? 6,88 Hemoglobin S results from the substitution of valine for glutamic acid at the sixth residue of the B polypeptide chain of hemoglobin?e Such a substitution renders the cell sensitive to low oxygen tension (pO2 < 70 mm Hg)? When low oxygen tension occurs, there are alterations of the shape of the red corpuscles. Sickled red blood cells have greater mechanical fragility, are more liable to hemolysis, have a shorter life span 3s and a greater viscosity15a~ than normal red blood cells. Once sickling occurs and viscosity of the blood increases, there is vascular stasis that in turn causes tissue hypoxia and acidosis, leading to further sickling, and thus perpetuating the vicious cycle of sickling? a2,~5,19,~~ If the cycle is allowed to continue, there is infarction of tissue that results in severe generalized pain and sometimes death. 8 The most definitive diagnostic tool for sickle cell disease is hemoglobin electrophoresis? 6,~7This confirms the presence of the abnormal hemoglobin, which is a qualitative diagnosis. The difference between sickle cell disease and sickle cell trait is one of the amount of hemoglobin S present, which is a quantitative diagnosis?5,25 Although it is generally felt that the trait is an asymptomatic state, this is not always true. Given conditions of stressful environment, persons with the trait may rarely exhibit all of the complications attributed to the disease and may, not so rarely, die from general anesthesia. 12,24,25,a2,a8 The best treatment of sickle cell crisis is prophylaxis by strict avoidance of hypoxemia, acidosis, dehydration, infection, and hypothermia in the sickle-prone individual?2'~aT'~,a7 Drugs such as steroids, 762

hypotonic saline, urea, phenothiazines, and dextran have been used in crisis 18aS,s1with disappointing results. 17,2~,s8,35 There are insufficient data regarding cyanate therapy to support its use at the present time? ~,14,2g,46 Transfusion (partial exchange transfusion) is an effective way of breaking the vicious cycle of sickling by replacing the sickle cells with (normal) transfused cells.7,8a7,3~

Case Report This 49-year-old Negro woman was admitted to Temple University Hospital on August 9, 1976, complaining of the sudden onset of occipital headache and neck stiffness. She had a history of sickle cell disease (hemoglobin SS). She had secondary chronic pulmonary changes and a tendency to congestive heart failure, history of leg ulcers, aseptic necrosis of both hips and shoulders, and functional asplenia. She had been Australian antigen-positive since January, 1975. Her past neurological history was unremarkable. Examination. The patient was thin, alert, and oriented but with slow mentation. The neck was stiff. There was weakness of the left lower limb with hyperreflexia and a Babinski sign. Lumbar puncture showed an opening pressure of 90 mm H20 and was grossly bloody. A computerized tomogram was normal. On August 13, following partial exchange transfusion, four-vessel cerebral angiography showed an anterior communicating artery aneurysm. With the diagnosis of subarachnoid hemorrhage and aneurysm, epsilon aminocaproic acid was added to her therapeutic regimen. A technetium scintiscan demonstrated no evidence of cerebral ischemia. By August 24, the spinal fluid had cleared and the neurological examination had returned to normal. A second partial exchange transfusion was done in preparation for surgery. Operation. Surgery was carried out on August 25, 1976, via the gyrus rectus approach? 4 The dissection was facilitated by enflurane-induced hypotension (mean 50 mm Hg), spinal drainage, and urea. Postoperative Course. The patient awoke with a left hemiparesis and a right third nerve palsy. Her left hemiparesis resolved, but her third nerve palsy remained. She was otherwise asymptomatic. Hemoglobin elecJ. Neurosurg. / Volume 47 / November, 1977

Aneurysm and sickle cell anemia trophoresis showed hemoglobin A 70% and hemoglobin S 30%, obviating the need for exchange transfusion before postoperative angiography. Right carotid angiogram on September 2 demonstrated clipping of the aneurysm and vasospasm. Repeat technetium scintiscan showed no change in perfusion over the preoperative scan. She was discharged home on September 15.

in these individuals provided certain basic guidelines are followed. Oduro and Searle 32 advocate simple, safe techniques with adequate oxygenation, ventilation, maintenance of circulating volume, and efficient pre-, inter-, and postoperative care in the management of the sickle cell patient in general. Preoperatively, infections should be vigorously sought for and treated. Pre-existing changes in organs such as Discussion kidney, liver, heart, and lungs that will conAngiography is the initial problem en- tribute to the perioperative hazard should countered in the management of patients with also be sought for and corrected. 3 sickle cell disease and subarachnoid hemor- Preoperative hemoglobin should be at least rhage. In 1965, Cheatham and Brackett9 8 gm. Care must be taken, however, to avoid demonstrated that in vitro sickling occurred cardiac overload with too vigorous a prewhen they mixed hemoglobin SS blood with operative transfusion. Respiration depressant contrast agents. On the basis of these find- drugs should be avoided for preoperative ings, they recommended that a minimum of sedation. Preinduction oxygen should be contrast material be used in these patients. given for at least 5 minutes. Induction is done Fortunately, by means of partial exchange by halothane or diethyl ether. Paralysis for transfusion, the amount of hemoglobin S can intubation is by a short-acting muscle relaxbe reduced to 40% or less, and angiography ant. Anesthesia is maintained by nitrous oxcan proceed in relative safety. ide and oxygen or halothane. Blood loss is Nadel and Spivack 8~ recommended replaced adequately and immediately.1~ transfusion of packed normal red blood cells Urea was our choice over mannitol and in order to provide greater oxygen-carrying furosemide for reduction of brain volume capacity in the preoperative sickle cell because it has been used safely in the patient. Subsequent reports 7,8 have described attempted treatment of crisis. 31 Although its methods of partial exchange whereby the use in crisis is questionable) 7 some believe amount of hemoglobin S is reduced to 40% or that urea is able to prevent intraoperative less, thus temporarily converting the patient's crisis.lO,~o blood into hemoglobin SA, and making him a During the controlled hypotension of aneubetter anesthetic and surgical risk) Of the rysm surgery, arterial and venous blood gases methods reported, the one by Charache 8 is and the mean systolic and central venous best because only abnormal blood (hemo- blood pressures should be monitored. In our globin SS) is removed and discarded and case, the blood pressure was easily lowered by there is only minimal change in blood the anesthetic alone (enflurane). If a hypotenvolume. sire agent had been necessary, our choice Epsilon aminocaproic acid has had applica- would have been s o d i u m nitroprusside tion in intractable hematuria, a complication because of its potency, its immediate action, of sickle cell disease, e,~2 Its use is therefore its evanescent effects, its minimal effect upon probably not contraindicated in these patients cardiac output, and its minimal toxicity over with ruptured aneurysm. Likewise, bar- a short course? a biturates and steroids, although of no benefit Postoperative angiography should be done in crisis, have had considerable use in sickle whenever feasible, TM preferably within several cell disease and are probably safe to use? 7 days after surgery while the hemoglobin A is Anesthesia in the patient with sickle cell still at an acceptable level (> 60%). disease (hemoglobin SS) then, after exchange It should be emphas.ized that angiography, transfusion, should be no different and no surgery, and anesthesia of this type in a riskier than that in the individual with the patient with undetected sickle cell trait trait (hemoglobin SA). Under usual cir- (hemoglobin SA) can result in catastrocumstances, the trait should pose no special phe. ~2,2",25,",'1 For this reason, all suspected risk to general anesthesia) We believe that individuals should be given a sickle cell hypotensive anesthesia can also be safely used screen) 5,28,~e,~7 Once diagnosed, a sickle cell J. Neurosurg. / Volume 47 / November, 1977


R. A. C l o s e a n d W . A. B u c h h e i t trait patient (hemoglobin SA) should be treated the s a m e (with the exception of exchange transfusion) as the patient with sickle cell disease (hemoglobin S S ) ? 2

8. 9.


1. The sickle cell gene is prevalent in the N e g r o population in the Uniled States and poses potential threat to life during angiography and m a j o r surgery. All suspected individuals should be screened. 2. Subarachnoid h e m o r r h a g e is rarely a c o m p l i c a t i o n of sickle cell disease and therefore ruptured a n e u r y s m and other causes should be sought when it is discovered in these patients. 3. Angiography and hypotensive anesthesia can be carried out safely after hemoglobin A is raised to 60% by means of partial exchange transfusion. 4. Even a f t e r e x c h a n g e transfusion, anesthesia techniques should scrupulously avoid hypoxemia, h y p o t h e r m i a , and acidosis. 5. The blood volume m u s t be maintained during the postoperative period.

10. 11.


13. 14.



Thanks are offered to Mark Kaplan and Howard Edelman for research assistance, to Michael Scott, M.D., and James V. Harp, M.D., for their kind critical review, and to M. Amy Wischum for preparation of the manuscript. References 1. Adam~" RD Riggs RE, Rupp C: Clinical pathologic conference. Neurology 4:705-709, 1954 2. Adeloye A, Ogbeide MI, Odeku EL: Massive intracranial hemorrhage in sickle cell anemia. Neurology 20:1165-1170, 1970 3. Atlas SA: The sickle cell trait and surgical complications: a matched-pair patient analysis. JAMA 229:1078-1080, 1974 4. Baird RL, Weiss DL, Ferguson AD, et al: Studies in sickle cell anemia. XXI. Clinicopathological aspects of neurological manifestations. Pediatrics 34:92-100, 1964 5. Ballard HS, Bondar H: Spontaneous subarachnoid hemorrhage in sickle cell anemia. Neurology 7:443-444, 1957 6. Bilinsky RT, Kandel GL, Rabiner SF: Epsilon aminocaproic acid therapy of hematuria due to heterozygous sickle cell diseases. J Urol 102:93-95, 1969 7. Brody JI, Goldsmith MH, Park SK, et al: Symptomatic crises of sickle cell anemia 764

16. 17. 18. 19.

20. 21. 22.

23. 24. 25.

treated by limited exchange transfusion. Ann Intern Med 72:327-330, 1970 Charache S: The treatment of sickle cell anemia. Arch Intern Med 133:698-705, 1974 Cheatham ML, Brackett CE: Problems in management of subarachnoid hemorrhage in sickle cell anemia. J Neurosurg 23:488-493, 1965 Coplans M: Sickle cell problems - anesthetics. Proc R Soc Med 67:1072-1073, 1974 de Furia FG, Miller DR, Cerami A, et al: The effects of cyanate in vitro on red blood cell metabolism and function in sickle cell anemia. J Clio Invest 51:566-574, 1972 deLeval MR, Taswell HF, Bvwie EJW, et al: Open heart surgery in patients with inherited hemoglobinopathies, red cell dyscrasias, and coagulopathies. Arch Surg 109:618-622, 1974 Drake CG, Allcock JM: Postoperative angiography and the "slipped" clip. J Neuresurg 39:683-689, 1973 Gillette PN, Manning JM, Cerami A: Increased survival of sickle-cell erythrocytes after treatment in vitro with sodium cyanate. Proc Natl Aead Sci USA 68:2791-2793, 1971 Greenberg MS, Kass EH, Castle WB: Studies on the destruction of red blood cells. XII. Factors influencing the role of S hemoglobin in the pathologic physiology of sickle cell anemia and related disorders. J Clin Invest 36: 833-843, 1957 Greer M, Schotland D: Abnormal hemoglobin as a cause of neurologic disease. Neurology 12:114-123, 1962 Guy RB, Rothenberg SP: Sickle cell crisis. Med Clin North Am 57:1591-1598, 1973 Guy RB, Rothenberg SP: Treatment of sickle cell crisis with hypotonic saline. Clin Res 19:420, 1971 (Abstract) Harris JW, Brewster HH, Ham TH, et al: Studies on the destruction of red blood cells. X. The biophysics and biology of sickle-cell disease. Arch Intern Med 97:145-168, 1956 Herrick JB: Peculiar elongated and sickleshaped red blood corpuscles in a case of severe anemia. Arch Intern Med 6:517-521, 1910 Hughes JG, Diggs LW, Gillespie CE: The involvement of the nervous system in sickle-cell anemia. J Pediatr 17:165-184, 1940 Immergut MA, Stevenson T: The use of epsilon amino caproic acid in the control of hematuria associated with hemoglobinopathies. J Urol 93:110-111, 1965 Isaacs WA, Effiong CE, Ayeni O: Steroid treatment in the prevention of painful episodes in sickle-cell disease. Lancet 1:570-571, 1972 Jones SR, Binder RA, Donowho EM Jr: Sudden death in sickle-cell trait. N Engi J Med 282:323-325, 1970 Konotey-Ahulu FID: Anaesthetic deaths and

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Aneurysm and sickle cell anemia the sickle-cell trait. Lancet 1:267-268, 1969 37. Rubenstein E: Studies on the relationship of temperature to sickle cell anemia. Am J Med (Letter) 30:95-98, 1961 26. Kosnik EJ, Hunt WE: Postoperative hypertension in the management of patients with in- 38. Schenk EA: Sickle cell trait and superior longitudinal sinus thrombosis. Ann Intern Med tracranial arterial aneurysms. J Neorosnrg 60:465--470, 1964 45:148-154, 1976 27. Kraus AP: Clinical trials of therapy for sickle 39. Spigelman A, Warden M J: Surgery in patients with sickle cell disease. Arch Sorg 104: cell vaso-occlusive crises. Blood 42:979, 1973 761-764, 1972 (Abstract No. 7) 28. Leachman RD, Miller WT, Atias IM: Sickle 40. Spooner TR, Dark AW: The management of sickle cell patients undergoing surgery. cell trait complicated by sickle cell thrombi Laryngoscope 86:506-508, 1976 after open-heart surgery. Am Heart J 74: 41. Stockman JA, Nigro MA, Mishkin MM, et 268-270, 1967 al: Occlusion of large cerebral vessels in sickle29. May A, Bellingham A J, Huehns ER, et al: cell anemia. N Eng! J Med 287:846-849, 1972 Effect of cyanate on sickling. Lancet 1: 42. Sydenstricked VP, Mulherin WA, Houseal 658-661, 1972 RW: Sickle cell anemia; report of two cases in 30. Nadel JA, Spivack AP: Surgical management children with necropsy in one case. Am J Dis of sickle cell anemia: the use of packed red Child 26:132-154, 1923 blood cell transfusions. Ann Intern Med 48: 43. Tuzel IH: Sodium nitroprusside: a review of 399-406, 1958 its clinical effectiveness as a hypotensive 31. Nalbandian RM, Shultz G, Lusher JM, et al: agent. J Clin Pharmacol 14:494-503, 1974 Sickle cell crisis terminated by intravenous urea in sugar solutions - - a preliminary 44. VanderArk GD, Kempe LG, Smith DR: Anterior communicating aneurysms: the gyrus report. Am J Med Sci 261:309-324, 1971 rectus approach. Clin Neurosurg 21:120-133, 32. Oduro KA, Searle JF: Anaesthesia in sickle 1974 cell states: a plea for simplicity. Br Med J 45. Wertham F, Mitchell N, Angrist A: The brain 4:596-598, 1972 in sickle cell anemia. Arch Neurol Psychiatry 33. Oski FA, Viner ED, Purugganan H, et al: Low 47:752-767, 1942 molecular weight dextran in sickle-cell crisis. 46. Wintrobe MM: Clinical Hematology, ed 7. J A M A 191:43, 1965 Philadelphia: Lea and Febiger, 1974, 1896 pp 34. Pauling L, Itano HA, Singer S J, et al: Sickle cell anemia, a molecular disease. Science 47. Wintrobe MM, Thorn GW, Adams RD, et al: Harrison's Principles of Internal Medicine, ed 110:543-548, 1949 7. New York: McGraw-Hill, 1974, 2044 pp 35. Pearson HA, Noyes WD: Failure of phenothiazines in sickle cell anemia. J A M A 199:33-34, 1967 36. Portnoy BA, Herion JC: Neurological Address reprint requests to: Richard A. Close, manifestations in sickle cell disease: with a review of the literature and emphasis on the M.D., Department of Neurosurgery, Temple prevalence of hemiplegia. Ann Intern Med University Hospital, 3401 North Broad Street, Philadelphia, Pennsylvania 19140. 76:643-652, 1972

J. Neurosurg. / Volume 47 / November, 1977


The management of ruptured intracranial aneurysm in sickle cell anemia. Case report.

J Neurosurg47:761-765, 1977 The management of ruptured intracranial aneurysm in sickle cell anemia Case report RICHARD A. CLOSE, M . D . , AND WILLI...
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