J Neurosurg 65:48-62, 1986 Observations on the perioperative management of aneurysmal subarachnoid hemorrhage S. SAM FINN, M.D., SIGURDUR A. STEPHENSEN, M.D., CAROLE A. MILLER, M.D., LAURA DROBNICH, R.N., AND WILLIAM E. HUNT, M.D. Division of Neurologic Surgery, Department of Surgery, Ohio State University Hospitals and Riverside Methodist Hospital, Columbus, Ohio v" Thirty-two patients with aneurysmal subarachnoid hemorrhage (SAH) were managed according to a protocol based on pain control and hemodynamic manipulation, monitored by an arterial line and SwanGanz catheter. Hemodynamic parameters were adjusted to four clinical situations. 1) For the unoperated patient with no neurological deficit, the regimen aims to maintain pulmonary wedge pressure (PWP) at 10 to 12 mm Hg, and the cardiac index (CI) and blood pressure (BP) at normal levels. 2) For the unoperated patient presenting with or developing neurological deficit, the PWP is increased until the deficit is reversed or the CI falls; the CI is high, and the BP normal. 3) For the postoperative patient with no neurological deficit, the PWP is maintained at 12 to 14 mm Hg, the CI is a high normal, and the BP is normal. 4) For the postoperative patient developing neurological deficit but showing no surgical complication on the computerized tomography scan, the PWP is increased until the deficit is reversed or the CI falls; the CI is high and the BP is increased with vasopressors if necessary. Fourteen patients developed neurological deficits either preoperatively, postoperatively, or both. Neurological deficits were repeatedly reversed by increasing the PWP, as measured hourly. In several patients an optimal wedge pressure was determined, below which deficits would reappear. In one patient whose neurological deficit was reversed on several occasions by increasing the PWP, the optimal PWP rose after each episode until it reached 22 mm Hg. Detailed event-related analysis of these patients' course illustrates these phenomena well. The optimal PWP varied from patient to patient, but ranged most frequently from 14 to 16 mm Hg. Meticulous monitoring of the patients' neurological status coupled with prompt correction of low PWP (assuming an adequate CI) has proven to be an effective way to prevent and reverse neurological deficits following aneurysmal SAH. 9 cerebral aneurysm 9 vasospasm 9 cerebral ischemia subarachnoid hemorrhage 9 pulmonary wedge pressure 9 cardiac index KEY WORDS W HILE technical advances have been made in the treatment of intracranial aneurysms, the morbidity and mortality associated with aneurysmal subarachnoid hemorrhage (SAH) remain high. The greatest problem is the prevention of cerebral infarction, seemingly secondary to the vasoconstrictive arteriopathy called "vasospasm. "4'8'20'22'29'44'66"74'78'79'92' 96,98,103,104 Attention has recently been drawn to three approaches aimed at preventing such cerebral ischemia. 1) Results of administration of calcium channel blockers such as nimodipine are currently being investigated. Some preliminary reports are favorable. 5-7,12,23,24,63 48 9 2) Early operation with a view to removing cisternal blood clots has been advocated. 73'94'1~ 3) Fluid administration, with or without induced hypertension, has recently received the widest acclaim. It is the cornerstone of perioperative management in aneurysmal SAH for many neurosurgeons. 35'46'5~176 The second problem in the management of aneurysmal SAH is recurrent hemorrhage from an unclipped aneurysm. The use of antifibrinolytic agents such as epsilon aminocaproic acid (EACA) appears widespread; however, it is by no means universally favored since there are complications associated with its use. Early J. Neurosurg. / Volume 65 ~July, 1986 Management of subarachnoid hemorrhage TABLE 1 Clinical summary of 32 patients with aneurysmal SAH* Case Age (yrs), Admission No. Sex Gradet 1 2 3 4 5 6 7 47, F 76, F 57, F 37, F 57, F 22, F 52, F 8 9 10 37, F 54, F 41, M Il Operation PWP (mm Hg) Day~c Grader Day~ Site Admission 0 0 I I II II II --1 1 5 1 3 0 0 I I II I II --1 2 5 2 4 It PCA (giant) rt ICA rt ICA rt ICA rt ICA rt MCA It MCA & basilar tip (not operated) 12 10 13 11 14 18 4 II II II II II 1 3 0 It ICA (giant) rt ICA ACoA 10 14 II 0 2 0 14 39, F II 0 II 1 12 13 14 35, M 53, F 42, M II 1I III 5 0 30 II II III 5 0 65 rt ICA, (PCoA & ICA bifurcation) ACoA rt ICA ACoA 14, 18 21-22 15 59, M llI 0 II 16 16 44, F III 0 17 18 19 20 35, F 44, F 74, F 43, M III III III III 21 43, F 22 23 24 12 Optimal 14 14 16 10 10 not operated rt MCA, It ICA rt ICA 13 14 0 0 0 0 II 9 I 1 not operated V 17 rt MCA rt ICA ACoA rt MCA 13 14 10 10 III 0 V 16 It MCA 12 60, F 40, F 56, M III III IV 0 0 0 II III II 12 16 38 rt ICA rt ICA (giant) It MCA 22 (CI = 1.9) 21 (CI = 1.95) 13 16 25 26 59, M 44, F IV IV 0 0 II I 16 29 7 19 16 27 28 29 30 31 32 70, M 50, F 70, F 66, M 57, M 60, M IV V V V V V 0 0 0 0 0 0 not operated not operated not operated not operated not operated not operated rt PICA rt carotid ophthalmic artery, rt ICA (bifurcation) -rt ICA --rt ICA rt ICA (giant) Complications Outcome It 3rd nerve paresis none UTI none DVT none MCA branch occluded at surgery, causing dysphasia, UTI none UTI, hydrocephalus none excellent excellent excellent excellent excellent excellent fluent dysphasia none excellent sepsis, hydrocephalus allergy to dye UTI with sepsis • 2, rebleed • 2, hydrocephalus none improving excellent improving at discharge, no deficit excellent rebled 14th day postSAH none none none rebled 17th day postSAH, pancreatitis rebled 16th day postSAH UTI, hydrocephalus UTI sepsis, pneumonia X 2, UTI • 2, fluid overload, epidural hemorrhage pneumonia UTI died 16 20 excellent excellent excellent excellent excellent excellent died died good excellent excellent excellent excellent died died died died died died 11 -12 -- * SAH = subarachnoid hemorrhage; PWP = pulmonary wedge pressure; - - = not recorded; PCA = posterior cerebral artery; 1CA = internal carotid artery; MCA = middle cerebral artery; UTI = urinary tract infection; DVT = deep vein thrombophlebitis; ACoA = anterior communicating artery; PCoA = posterior communicating artery; PICA = posterior inferior cerebellar artery; CI = cardiac index. t Grade according to Hunt and Hess. 45 $ Day post-hemorrhage. operation appears to have become more frequent in recent years, minimizing the hazard of early rebleeding. We have formulated a perioperative management regimen based upon laboratory-derived theory and clinical o b s e r v a t i o n . J. Neurosurg. / Volume 65 ~July, 1986 Clinical Material and Methods Patient Population Thirty-two patients have been treated according to o u r p r o t o c o l . T h e c o u r s e o f t h e s e p a t i e n t s is s u m m a r i z e d i n T a b l e 1. G r a d i n g o f s u r g i c a l r i s k w a s p e r f o r m e d 49 S. S. Finn, et al. TABLE 2 Grades of surgical risk at admission and operation Grade* No. Cases At Admission No. Cases At Operation 0 I II III IV V no. of cases 2 2 9 10 4 5 32 2 5 13 2 0 2 24 * Grade accordingto Hunt and Hess.45 according to the classification of Hunt and Hess. 45 Table 2 shows an analysis of grades at admission versus grades at operation. The two Grade V patients who underwent surgery were admitted in Grade III and rebled in the hospital. All patients who were classified in Grade V on admission died shortly thereafter. There were 11 men and 21 women, ranging in age from 22 to 76 years, with an average age of 55 years. Thirty-two aneurysms were identified at angiography. They were distributed as follows: 15 aneurysms arising from the internal carotid artery (ICA), five from the middle cerebral artery (MCA), four from the anterior communicating artery, one from the posterior inferior cerebellar artery, and one from the posterior cerebral artery. In addition, there were three cases of multiple aneurysms: one patient had carotid-ophthalmic and ICA bifurcation aneurysms, one had MCA and basilar tip aneurysms, and one had ICA bifurcation and posterior communicating artery aneurysms. Three patients did not undergo angiography. Management Methods A computerized tomography (CT) scan is initially obtained for all patients. 28'39Four-vessel angiography is performed as soon as the diagnosis of SAH is established. All patients are admitted to the intensive care unit where an indwelling arterial line and Swan-Ganz catheter are inserted and baseline blood pressure (BP), pulmonary wedge pressure (PWP), and cardiac index (CI) are determined. Routine laboratory studies are obtained. At our institution, patients in Grades I and II are taken to surgery as soon as possible (assuming no significant vasospasm on angiography), while those in Grades III to V are managed conservatively until such time as they improve to Grade I, IA, o r II. 45-47 Recently, some Grade III patients with minimal deficit and no vasospasm have undergone early surgery. Our management regimen is designed to deal with four problems common to all patients with aneurysmal SAH: pain, hypertension, hypovolemia, and disturbances of blood gas, serum electrolyte, and glucose levels. Pain control is achieved by intravenous injections of meperidine (Demerol) at doses of 25 to 50 mg initially, then 25 mg every 2 hours as needed. Control of BP, 50 in our experience, is achieved largely by the administration of meperidine alone. However, for patients who require antihypertensive medication, we give sodium nitroprusside (100 mg in 250 cc of 5% dextrose in water) by continuous infusion with constant BP monitoring by arterial line. Cardiovascular function is continuously monitored by means of a Swan-Ganz catheter. The PWP or pulmonary artery diastolic pressure (PADP) is recorded hourly, along with central venous pressure (CVP). The CI is determined by the thermodilution method every 6 hours or as needed. Blood gas, serum electrolyte, and glucose levels are determined every 6 hours and are promptly corrected if abnormal. A neurological assessment is performed at least hourly. 29 The protocol aims to achieve different cardiovascular parameters, depending upon the patient's status. Patients are classified into four situations: 1) Patients not undergoing surgery who have no neurological deficits. For these, the goal is to maintain the PWP at 10 to 12 mm Hg; to establish CI at 3 to 4 liters/min/sq m; and to keep the BP normal or as low as the neurological status permits. 2) In patients not undergoing surgery who present with or develop neurological deficits, the PWP is raised until the deficits disappear (the CI increases concomitantly). The BP is kept normal or as low as the neurological status permits. 3) In postoperative patients with no neurological deficits, the regimen aims to maintain the PWP at 12 to 14 mm Hg, the CI at 3.5 to 4.5 liters/min/sq m, and the BP at a normal level or as low as the neurological status will permit. 4) Postoperative patients with immediate or delayed neurological deficit receive a rapid fluid bolus (500 cc of hetastarch) less than 20 minutes after onset of symptoms. The PWP is increased. If the deficit does not disappear, additional fluid is given, first using hetastarch and thereafter fresh frozen plasma and hetastarch in equal quantities. The PWP is increased to maximal tolerable levels, and the patient is given digitalis. The BP is increased if these measures fail. Hypertension, as discussed by Kosnik and Hunt, 56 has been rare since the institution of aggressive volume replacement (see below). A C T scan is obtained promptly to rule out a surgical lesion, but the therapy described above is not delayed. In patients with preexisting heart disease who are prone to cardiac failure, ~6 we augment the CI with dobutamine and afterload reduction, if necessary. If possible, hematocrit is kept between 30% and 35%. Intracranial pressure (ICP) monitoring is instituted in cases of severe neurological deterioration, or edema with shift or hydrocephalus on the CT scan. 4~ 12 All patients are fitted with sequential compression stockings to prevent deep vein thrombophlebitis. We have recently begun to administer peripheral parenteral nutrition from admission in patients who cannot be fed orally. All patients receive dexamethasone, 4 to 10 mg intravenously every 6 hours, cimetidine, 300 mg intravenously every 6 hours, and phenytoin or phenobarbital J. Neurosurg. / Volume 65 ~July, 1986 Management of subarachnoidhemorrhage for seizure prophylaxis. The PWP is maintained at the required level for at least 5 days and then gradually lowered. The Swan-Ganz catheter is removed if the patient has shown no neurological deterioration after 72 hours at a normal PWP. Results Reversal of Neurological Deficits Fourteen patients developed neurological deficits, presumably due to cerebral ischemia caused by vasospasm, either preoperatively, postoperatively, or both. Neurological deficits appeared and were reversed 32 times in these 14 patients; in only one patient (Case 12) were we unable to reverse neurological deterioration. In analyzing the course of these events, we have made the following observations: 1) neurological deficit is preceded by a fall in PWP of about 1 hour's duration; 2) the less pronounced the deficit, the more easily it is reversed; 3) there is a time lag of 1 to 2 hours between increasing the PWP and the disappearance of a neurological deficit; and 4) neurological deficits related to acute hypotension are, by contrast, immediately reversed by raising the BP. Correlation of PWP with Neurological Deficit In six patients who developed repeated neurological deficits, we were able to observe an "optimal" PWP below which such deficits would appear and above which they would disappear. This phenomenon, when observed, is extremely useful in guiding the hemodynamic management of these patients. The actual optimal PWP values were 10 mm Hg in one patient and 14 to 16 mm Hg in four patients. In one patient (Case 10), the PWP necessary to overcome the deficit rose after each episode. Raising PWP to very high levels (greater than 18 mm Hg in a normal heart) is not a routine measure, but seemed to be necessary in three patients, as evidenced by neurological improvement. The Role of Cardiac Index While CI was uniformly high (4 to 5.5 liters/min/sq m) in all patients in whom neurological deficits were reversed, PWP or PADP was observed to correlate much more closely with the deficits, and thus proved to be a more sensitive parameter, especially as continuous monitoring of PADP is possible. The Role of Induced Hypertension In this series, we did not encounter the hypovolemia and hypotension that was common in the past because the entire management regimen precludes this catastrophic event. Should it occur, vasopressors are used at once as volume expansion is begun. Hypertension is not usually induced by the administration of large fluid volumes alone. Vasopressors have been used in conjunction with extremely high PWP only as a last resort in the three patients mentioned above. J. Neurosurg. / Volume 65 ~July, 1986 Rebleeding The risk of rebleeding is minimized by early operation and control of BP. Four patients in this series rebled. All were Grade III patients whose neurological status was poor, and all but one had severe associated medical problems. Three of these patients (Cases 16, 20, and 21) rebled fatally between the 14th and 17th day after SAH. None of these patients was hypertensive at the time of rebleeding and all were improving neurologically. The fourth patient (Case 14), the only one of the four who rebled while receiving EACA, had two minor rebleeds. He was moderately hypertensive at the time of his first rebleed. We do not administer EACA routinely, but six patients were injected with EACA, 24 gm/day intravenously. Residual Neurological Deficits In one patient (Case 7), the posterior temporal branch of the MCA was occluded at the time of clipping. She developed a fluent dysphasia which has largely cleared. As mentioned above, one patient (Case 12) developed neurological deficits that could not be reversed. Complications No instances of catheter sepsis were noted. There were no cases of pneumothorax or cardiac complications associated with the use of Swan-Ganz catheters. All episodes of sepsis, usually renal or pulmonary, occurred in patients whose stay in the intensive care unit exceeded 14 days. One patient (Case 16) had bronchopneumonia on admission which necessitated intubation. Two other patients (Cases 22 and 23) had heart failure on admission prior to any fluid administration and required inotropic drugs coupled with afterload reduction. One patient (Case 13) proved to be allergic to angiographic contrast material, and another (Case 5) developed deep vein thrombophlebitis. One patient (Case 24) developed subacute postoperative epidural hemorrhage which was evacuated. This same patient was the only one in this series who developed fluid overload with resulting hypoxia, but without a decrease in CI. There were no instances of profound electrolyte imbalance or hyperosmolar state. Eight patients developed urinary tract infections, all successfully treated with antibiotics. Illustrative Case Reports The following case reports illustrate the use of this regimen in three critical cases. Case 10 This 41-year-old man presented 12 hours after the sudden onset of severe headache which awakened him from sleep. There was associated vomiting and photophobia. Neurological examination was normal, but the neck was stiff. The basal cisterns were opacified on CT scans. The initial diagnosis was SAH, Hunt and Hess 51 o~ o~ e~ o't FIG. 1. Case 10. A: S u m m a r y of course during post-hemorrhage days ( P H D ) 1 to 8. P W P = p u l m o n a r y wedge pressure; C V P = central venous pressure; SBP = systolic blood pressure; H C T = hematocrit (%); S-G = S w a n - G a n z catheter. M o t o r scale: 1 = normal, 4 = hemiplegia. B: Angiograms o n a d m i s s i o n showing a n anterior c o m m u n i c a t i n g artery a n e u r y s m with n o vasospasm. C: C o m p u t e r i z e d t o m o g r a p h y scans o n admission showing s u b a r a c h n o i d hemorrhage. D: Scans o n P H D 6 showing a lucency in the distribution of the right anterior cerebral artery. Management of subarachnoid hemorrhage Grade II. Immediate arteriography revealed an anterior communicating artery aneurysm. The patient was operated on at once and the aneurysm clipped (Fig. 1). The first 3 postoperative days were uneventful. He was extubated 12 hours postoperatively, and the SwanGanz catheter was removed on the 3rd postoperative day. The following day he developed a mild left hemiparesis. Central venous pressure was 6 cm H20, but BP was unchanged. A 300-ml bolus of hetastarch was given at once and the Swan-Ganz catheter was reinserted. Following this fluid bolus, PWP was 12 m m Hg and CI was 4.6 liters/min/sq m. After a total of 750 ml betastarch had been administered, the PWP had risen to 14 to 16 mm Hg, CI and CVP were unchanged, and the hemiparesis resolved. A C T scan showed a lucent region in the medial right frontal lobe without displacement of the ventricles or midline structures. Five days after surgery, the PWP dropped to 4 mm Hg without a change in CVP, BP, or CI. The patient developed an increasing left hemiparesis. One liter of hetastarch and 500 ml packed red cells were given, whereupon PWP rose to 16 to 22 mm Hg with arrest of the progressive hemiparesis. During the night, PWP drifted down to 12 mm Hg. Two hours later, he developed a profound left hemiplegia with drowsiness and disorientation. The CI was 5.4 liters/min/sq m. A C T scan showed the same radiolucent lesion of the fight medial frontal lobe as before. The patient was intubated and given 500 ml hetastarch, 1 liter fresh frozen plasma, and 1 liter packed red cells until his PWP was greater than 18 mm Hg. He was given digitalis and dopamine to maintain BP above 160 mm Hg systolic. Over the next 8 hours, he was again able to move his left side. By the 7th postoperative day, he had only a mild hemiparesis; PWP was maintained between 18 and 20 mm Hg. On the evening of the 8th and the morning of the 9th day after surgery, the PWP dropped to 14 to 17 mm Hg for a period of 10 hours, and shortly thereafter the patient again developed a dense left hemiplegia (Fig. 2). The CI was 5.2 liters/min/sq m and CVP was 10 to 14 cm H20. Two liters of fluid were given. The hemiplegia resolved to a minimal hemiparesis when the PWP was maintained at 20 to 22 mm Hg for about 4 hours. On the 10th day, the PWP dropped to 15 m m Hg and left hemiplegia developed for the fourth time. Central venous pressure was 20 cm H~O and CI was 5.4 liters/min/sq m. Fluid was given until the PWP was 21 to 25 mm Hg. The hemiparesis again became minimal. Over the next 2 days, PWP exceeded 21 mm Hg. On the 12th day after SAH, the patient's strength was normal. Over the next 3 days, the PWP was gradually allowed to fall without recurrent neurological deficits. Throughout most of his course, the serum sodium level ranged between 131 and 135 mEq/liter, except for one occasion on the 5th day postoperatively when it was 128 mEq/liter. The hematocrit ranged between 27.5% and 36.8%. The patient has made a full recovery. J. Neurosurg. / Volume 65 ~July. 1986 Case 12 This 35-year-old man presented 5 days after SAH at Grade II. The initial CT scan and angiogram showed a left frontal hemorrhage and an anterior communicating artery aneurysm without vasospasm. His BP on admission was 180/110 mm Hg and fell to 130/80 mm Hg after he was given 25 mg meperidine intravenously. He underwent a left frontal craniotomy and uneventful clipping of his aneurysm. In the recovery room, he was noted to have extensor posturing on his left side. His pupils were round and reactive. Blood pressure was 160/90 m m Hg, PWP was 0 to 2 m m Hg, and CI 1.95 liters/min/sq m. He was given 3000 ml of fluid, which increased PWP to 20 to 22 m m Hg and CI to 5.5 liters/ min/sq m where they were kept. A C T scan was normal. A needle ventriculostomy revealed an ICP of 16 mm Hg. Despite the fact that the PWP was maintained at 18 to 22 mm Hg and systolic BP at 180 mm Hg, the patient's condition continued to decline. His ICP began to rise, and repeat CT 8 days after SAH showed marked edema in the territory of both anterior cerebral arteries. He was placed on high-dose barbiturates and dopamine to maintain his BP. Peripheral parenteral nutrition was instituted. The patient developed diabetes insipidus, which was easily controlled with injectable desamino-cis-l-8-Darginine vasopressin (DDAVP). His Swan-Ganz catheter was changed six times. He also developed sepsis secondary to pneumonia which was reversed by antibiotic therapy. After 16 days, when his ICP had declined to normal values, barbiturates were discontinued. On the 30th day after SAH he began to follow commands, moving first his fight side and then his left, but only slightly. A tracheostomy and gastrostomy were performed and he was sent for rehabilitation. After 1 year, he is ambulatory and is beginning to talk and interact with his family. This case illustrates a partial failure to control the ischemic crisis. Case 24 This 56-year-old man suffered an SAH and was brought to Riverside Methodist Hospital the same day with an admission status of Grade IV. His course is illustrated in Fig. 3. Initially, he was unresponsive to verbal stimuli. He was intermittently bilaterally decerebrate. His pupils were 3 mm in diameter and highly reactive. Admission BP was 180/110 mm Hg, pulse 120 beats/min, and respirations 30 to 40/min. The patient was electively intubated by the nasal route. Intravenous meperidine (50 mg) was administered in the emergency room. His BP decreased to 130/90 mm Hg and his pulse to 100/min. A CT scan showed a hemorrhage in the left sylvian fissure with blood in the left lateral ventricle. He was taken to the intensive care unit, where a Swan-Ganz catheter was inserted. Initial PWP was 16 mm Hg and CI was 3.9 liters/min/sq m. Intravenous meperidine, 25 mg every hour, was required initially to stabilize and 53 o~ t.~ e~ r FIG. 2. Case 10. A: Summary o f course during post-hemorrhage days ( P H D ' s ) 9 to 16. P W P = pulmonary wedge pressure; C V P = central venous pressure; SBP = systolic blood pressure; H C T = hematocrit (%). Motor scale: 1 = normal, 4 = hemiplegia. B: Angiograms on P H D 19 showing the aneurysm clipped and residual angiographic vasospasm. C: Computerized t o m o g r a p h y scans on P H D 29 showing a small area o f contrast e n h a n c e m e n t in the distribution o f the right anterior cerebral artery. The patient was asymptomatic. (/3 Management of subarachnoid hemorrhage FIG. 3. Case 24. A: Summary of course during post-hemorrhage days (PHD's) 0 to 8. PWP = pulmonary wedge pressure; CVP = central venous pressure; SBP = systolic blood pressure; HCT = hematocrit (%). Motor scale: 1 = normal, 4 = hemiplegia. B and C: Computerized tomography scans on admission showing hemorrhage in the left sylvian fissure with blood in the left lateral ventricle. D: Angiogram on PHD 1 showing a left middle cerebral artery aneurysm. then to lower BP. Within 12 hours of admission, the patient was following commands and looking around. Angiography performed on the day after SAH revealed a left MCA aneurysm. The PWP was kept around 16 m m Hg. Three days after SAH, the PWP fell to 12 m m Hg; he then developed a right hemiparesis. J. Neurosurg. / Volume 65 ~July, 1986 A 300-ml bolus of hetastarch was necessary to increase PWP to 15 to 16 m m Hg and the deficit disappeared. The same day, there was another fall in PWP followed by right hemiparesis, which again resolved when the PWP was increased to 15 to 16 m m Hg. He became more alert and feeding via a nasoduodenal tube was 55 S. S. Finn, et al. started. The next day he again developed a fight hemiparesis following a drop in PWP, but this cleared following infusion of 300 ml fresh frozen plasma. He was again responsive and without neurological deficit. Administration of meperidine was reduced to every 2 hours as needed. The Swan-Ganz catheter was changed on the 5th day after SAH. The next day, PWP fell to 9 mm Hg. The right hemiparesis returned and the patient became drowsy. After a 200-ml bolus of hetastarch and 300 ml fresh frozen plasma was administered, the PWP rose to 17 mm Hg and the hemiparesis disappeared. However, 4 hours later there was another fall in PWP to 10 mm Hg, with reappearance of the right hemiparesis. The CI was 4.0 liters/min/sq m. The PWP was again raised with a fluid bolus and the hemiparesis disappeared. Thereafter, he recovered without residual deficit. His aneurysm was clipped without incident 38 days after the hemorrhage. Discussion In 1974, Hunt and Kosnik 46 first alluded to the concept of "overall mortality" in discussing the efficacy of management of SAH. This concept was expanded and reemphasized by Hunt and Miller47 and Post, et al.,84 in 1977. Weir and Aronyk 115called this "management morbidity and mortality." It is more significant than operative mortality and morbidity, since it can be quite low after recovery from SAH. 1~ The methods that we use rely upon meticulous and frequent assessment of the patient's neurological status, coupled with continuous monitoring of BP and cardiac function. To be effective, therapeutic intervention must be performed as soon as deterioration in neurological status is detected. Control of Pain There is, among neurosurgeons, a reluctance to use narcotics because of their tendency to depress respiration and the level of consciousness and to constrict the pupils. However, intravenous meperidine, 25 mg every 2 hours, does not cause drowsiness or affect pupillary function. Headache is effectively and promptly controlled. The patient's sensorium may even improve. Equally important, the patient becomes hemodynamically stable: BP is reduced and pulse and respiration rates are slowed. 33 Seven patients with prior hypertension required no antihypertensive medication when treated with this agent, which simplifies subsequent hemodynamic manipulations. Three patients experienced nausea after the first dose of meperidine, but tolerated it well thereafter. Some patients required 25 mg meperidine to be given intravenously each hour for a short period. We administer the drug on a scheduled basis for the first 24 to 48 hours and then as needed if the headache subsides. Narcotics are known to block the sympathetic response to pain and stress. 8~ Elevated circulating cate56 cholamines have been documented in SAH and are probably responsible for the hyperdynamic state (for example, tachycardia and hypertension) in which many of these patients present. We believe that pain is largely responsible for the release of catecholamines and that the administration of meperidine, by reducing pain, reduces systemic catecholamine release. Control of Blood Pressure Control of blood pressure, as emphasized by Rosenwasser, et al., 91 is of utmost importance in the management of patients with SAH. In reducing BP, we use the patient's level of consciousness as an indicator. 25 If there is increased ICP, a cerebral perfusion pressure (mean arterial BP minus ICP) of at least 70 mm Hg is maintained, z6 If BP does not respond to meperidine, sodium nitroprusside is the ideal agent because it can be easily and rapidly titrated. When thiocyanate has been used for several days, blood levels are determined. No instances of toxicity have occurred in our series, and tachyphylaxis is rare. It has been reported that sodium nitroprusside increases ICP, but we have not seen this. 17 Other antihypertensive agents are undesirable. Hydralazine, for example, may cause a precipitous fall in BP which cannot be promptly reversed. Betaadrenergic blocking agents such as propranolol (Inderal) carry the same risk, and also interfere with cardiac function (negative inotrope) and cerebral blood flow (CBF).9.z1,69 Diuretics have almost no place in the management of patients with SAH since they lower intravascular volume and are prone to cause electrolyte imbalance. Monitoring Cardiovascular Function Cerebral blood flow is related in part to systemic BP, cardiac function, and intravascular volume, especially when autoregulation is impaired. 21"36'7~ Adequate monitoring requires CI determinations and measurement of pulmonary artery pressures. 32"I~ The PWP is a close approximation of left atrial pressure, which in turn reflects left ventricular end diastolic (filling) pressure. Central venous pressure may not accurately approximate PWP, especially in the elderly and in patients with underlying heart and lung disease. 93,~~ Measurement of PWP requires a nursing maneuver, but PADP may be measured on a continuous basis and is equivalent to PWP. Without CI determinations, however, these readings are meaningless. The Swan-Ganz catheter provides the necessary data, but should be employed only by those thoroughly trained in its use. Swan-Ganz catheter insertion can be associated with several complications, such as infection, pneumothorax, hemothorax, ventricular arrhythmia, and pulmonary infarction. 75 We have noted no complications related to its use, mainly, we believe, because of our insistence on meticulous insertion techniques and maintenance. While the Swan-Ganz catheter data are essential to aggressive treatment, the CVP is a simple substitute if the more complex system is not available. J. Neurosurg. / Volume 65 ~July, 1986 Management of subarachnoid hemorrhage Volume Expansion, PWP, and Neurological Deficit In 1976, Kosnik and Hunt 56 reported their experiences with induced hypervolemia and hypertension in combating the effects of cerebral arterial spasm. Since that time, many authors have confirmed the efficacy of this treatment, and it seems to be the most effective method known of preventing cerebral ischemia, despite numerous descriptions of other methods, especially pharmacological. 30,31,43,98,99,117 Grubb, et al., 38 and others 15'41's8'71'72'82'83'127 have shown that CBF decreases progressively following SAH and that cerebral blood volume increases. Rosenstein, eta[., 9~ have described the value of a bedside CBF machine in managing patients with SAH, but although intravascular volume expansion was used, cardiovascular parameters were not alluded to. However, they did show that fluid administration was associated with an increase in CBF and reversal of neurological deficits. We keep the PWP within a range such that hypovolemia is unlikely? 3 Although it is difficult to refer to a normal PWP without reference to the CI, the range most often used (assuming an adequate CI) is 5 to 12 mm Hg in the "normal" heart. We, therefore, do not let the PWP fall below 10 mm Hg. If a patient presents with a PWP greater than 12 m m Hg and an adequate CI, we make no attempt to reduce it with diuretics. On the contrary, we keep the PWP at admission value, increasing it only if neurological deficits develop. Only one patient in this series presented with a low PWP. We use high-volume crystalloid infusion (greater than 100 cc/hour of 5% dextrose in normal saline) to maintain PWP. When a bolus injection is necessary, we use hetastarch and fresh frozen plasma. Although we try to titrate crystalloid infusion rates to a point where the necessity for a bolus is minimized, most patients still require 200 to 500 cc daily in bolus form. The properties of hetastarch as a volume expander and its use in neurosurgical patients have been well described. 3'61,87,1o6 Complications associated with its use include blood dyscrasias and liver dysfunction. We have not seen these complications. Maintenance of PWP is prophylactic as well as therapeutic. Most neurological deficits observed have been mild and easily reversed, but prompt action is necessary. Skilled nursing, sensitive to early changes in neurological function, is essential. A bolus of 200 to 500 ml fluid, increasing PWP by only 2 to 3 mm Hg, is often sufficient to reverse a neurological deficit if given promptly. Case 12 illustrates the consequences of failure to act quickly. This case also demonstrates the exquisite correlation between PWP and neurological deficits, despite hypertension and a high CI which did not change appreciably in response to increases in PWP. Since there have been several reports, especially those of Maroon and Nelson 68 and Kudo, et al., 57 documenting a decrease in blood volume following SAH, it would be desirable to monitor intravascular volume. However, isotopic measurements cannot be obtained J. Neurosurg. / Volume 65 ~July, 1986 on a continuous basis and the margin of error can be considerable. 2'6~ The cause of this fall in blood volume is uncertain, 113 but there are other reports in which blood volume was expanded with improvement in neurological function, suggesting that low volume is an important factor in the development of cerebral ischemia following S A H . 35'46'50"52'54'56'70'85'86'91'116Pulmonary artery diastolic pressure or PWP have been thought to reflect the intravascular volume status. However, Baek, et al., 13 have shown that there is only an approximate correlation between PWP/PADP and actual intravascular volume. A low PWP seems to be associated with low volume, but at higher PWP's the correlation is much less distinct. Since only small increases in PWP/PADP are sufficient to reverse neurological deficits in the majority of patients, the question arises as to whether we are in fact raising intravascular volume significantly. 42 In three of our patients, serial blood volume determinations (using the chromium-51 and iodine-125 radioactive iodinated serum albumin methods) before and after the development of neurological deficits failed to show any changes. If this is true, what exactly is the role of PWP in reversing cerebral ischemia? It certainly cannot be a direct one. McGillicuddy, et al., TM in their monkey model for vasospasm, found a significant increase in CBF following an increase of the animal's CVP. In the control hemisphere, where autoregulation was presumably intact, CBF did not increase. Since actual intravascular volume was not documented, it is difficult to ascertain whether they were dealing with actual hypervolemia or a hypovolemic state corrected to normovolemia. From a purely clinical standpoint, this is not important, since we are dealing with cardiovascular parameters alone. The Delayed Therapeutic Response As mentioned, there is often a delay of about 1 hour between a fall in PWP or PADP and the appearance of neurological deficits. Conversely, deficits will disappear 1 to 2 hours after PWP is increased. Such a "hysteresis" effect has been described as occurring with BP fluctuations in certain patients. 52 This is in sharp contrast to the situation with neurological deficits associated with acute hypotension, which is immediately reversed when the hypotension is corrected. There are no clues in the literature as to the physiological mechanisms coupling left atrial pressure, left ventricular end diastolic pressure, CI, and CBF. Our observations of the close correlation between PWP and neurological deficits (associated with a range of high CI and adequate BP) suggest to us that rheologic, humoral, or reflex factors are at play. However, Bates and Sundt 14 could not find any reflex correlation between cardiovascular function and CBF experimentally. Cardiac Index and Neurological Deficit Davis and Sundt 21 have shown the effects of cardiac output manipulation in the cat, but the role of PWP or 57 S. S. Finn, et al. left atrial pressure was not addressed. Pritz 85 described two patients in whom neurological deficits were reversed by increasing cardiac output. Those patients, however, were not monitored when they developed neurological deficits, and no mention of initial PWP was made. A cardiac output versus PWP curve has been determined, hence the importance of CI? 4'110In reviewing our data, it appears that CI was high (4 to 5.5 liters/ min/sq m) in all patients in whom neurological deficits were reversed. However, we observed several times a correlation between PWP and neurological deficits without appreciable change in CI (see Case 10). There may actually have been a change in CI too small to have been detected by the thermodilution method but, from a practical standpoint, PWP (or PADP) was the only parameter that we observed to correlate closely with neurological deficits. In patients with preexisting heart disease who are prone to cardiac failure, we augment CI to about 4 liters/min/sq m with dobutamine, and further if neurological deficits develop. Digitalis is given routinely. The manipulations needed to calculate the Starling curve entail a high risk of inducing heart failure and are therefore contraindicated. Induced Hypertension and Neurological Deficit Kosnik and Hunt 56 emphasized raising the BP first and expanding volume second. Certainly this is the correct approach if there is hypotension and hypovolemia. In our series, however, these two conditions were not allowed to occur, hence the present emphasis on PWP/PADP. As noted, we have repeatedly reversed neurological deficits without inducing hypertension. We induced hypertension in only three patients in this series; these were the only patients who developed profound neurological deficits. Extreme bradycardia and massive diuresis can be observed with high PWP. The use of vasopressin to blunt diuresis 5~ has not been necessary in our series and, in our opinion, carries a high risk of precipitating heart failure. Hemodilution and Neurological Deficit Several reports, 19'77,1~176176 including those by Wood, el al., 119-123'125 have emphasized the benefits of hemodilution and reduction of blood viscosity. They have found experimentally that intravascular volume expansion with whole blood (without hemodilution) fails to elevate CBF in regions of focal cerebral ischemia. TM The well-documented beneficial effects of hemodilution on cardiac output and CBF make this an attractive adjunct in the therapy of these patients. 37'38"59The risk is very low; we try to keep the hematocrit at 30% to 35%. We have not seen any correlation, however, between increased hematocrit and ischemic neurological deficits. Intraoperative Monitoring During anesthesia, there is a period of extreme vulnerability not fully appreciated in the past. We are 58 cautious about induced hypotension. ~7The Swan-Ganz catheter is important, and PWP/PADP and CI must not be allowed to faU.48 This can be difficult to achieve because of myocardial depression by certain agents used in neuroanesthesia (such as barbiturates). It may be necessary to use drugs, such as dobutamine, with positive inotropic effects. In Case 12, despite a technically very satisfactory procedure, the patient was decerebrate upon emergence from anesthesia. The BP was 160 mm Hg systolic, but PWP was 0 to 2 mm Hg and CI was 1.95 liters/min/sq m. Despite administration of 3000 cc fluid and increasing the PWP to 22 mm Hg and CI to 5.5 liters/min/sq m, this patient continued to deteriorate. We speculate that these events may have been prevented had we maintained the PWP and CI during anesthesia. The Rebleeding Problem Early obliteration of the aneurysm is, of course, the only sure means to prevent rebleeding. 12'45-47'5t'62-65'~~ How much surgical manipulation of cerebral arteries aggravates vasospasm is uncertain. Lowering BP may be effective, but rebleeding can occur in the face of a normal BP, as happened in three of the four patients who rebled. The fourth patient, who was spontaneously extremely hypertensive (BP 190 mm Hg systolic), had a BP of 160 mm Hg systolic when he rebled, and this BP was the lowest his neurological status would permit. The use of antifibrinolytic drugs, such as EACA and tranexamic acid, has received mixed reviews.~'Is'95'l~ Kassell and Torner, 5s in reporting preliminary observations from the Cooperative Aneurysm Study, showed that while the rebleeding rate was markedly reduced after the first 48 hours, the incidence of focal ischemic neurological deficit was significantly increased (32.4% in treated patients vs. 22.7% in untreated patients). Hydrocephalus was twice as frequent in those receiving antifibrinolytic agents as in those not receiving them. Thrombophlebitis and pulmonary embolus were not found to be significantly different in frequency between the two groups. In our series, only six patients were given EACA and none developed cerebral infarction. One of these six patients developed hydrocephalus. It would be interesting to know the blood volume status of those patients in the Cooperative Aneurysm Study who developed an ischemic deficit. Perhaps the ischemic deficit only developed in dehydrated patients. Other Factors Meticulous attention to oxygenation, ventilation, and electrolyte balance is essential. Hyponatremia, defined as a serum sodium level less than 135 mEq/liter, occurs in the majority of patients with SAH. 49'67This is caused by increased natriuresis rather than water retention in patients whose intravascular volume is adequate. 8~ For this reason it is our practice to treat hyponatremia by cautious infusions of 3 % sodium chloride. The entity of increased antidiuretic hormone secretion, with secondary hyponatremia associated with hypovolemia, has J. Neurosurg. / Volume 65/July, 1986 Management of subarachnoid hemorrhage been described 76 and treatment requires volume repletion. We maintain serum sodium above 130 mEq/liter. Urine electrolytes should be obtained in order to differentiate between water retention and salt wasting. Nutritional status in drowsy and perhaps hyperrnetabolic patients is important. We administer peripheral parenteral nutrition to all patients who are too ill to be adequately nourished enterally. We generally use 6.25 % to 10% Travasol (a crystalline amino acid solution), a final dextrose concentration of 6.25% to 10% with appropriate electrolytes, and 20% Intralipid (an intravenous fat emulsion). Although full caloric requirements cannot always be met, we have been impressed by the benefits of this nutrition. The peripheral route has a low incidence of complications. Conclusions Thirty-two patients have been managed according to a specific hemodynamic regimen. The protocol is based on pain control, BP management, and volume repletion, with maintenance of a low hematocrit. Serum glucose, electrolyte, and blood gas levels are kept in normal range. The following conclusions can be drawn: i. Pain control (intravenous meperidine, 25 mg every 2 hours) is essential to achieve hemodynamic stability and may well have other beneficial effects. 2. The PWP (or PADP) correlates most closely with neurological deficit (within a CI range of 4 to 5.5 liters/ min/sq m). 3. Frequent and meticulous neurological monitoring, coupled with prompt correction of inadequate PWP/ PADP, is the best method established to date of preventing neurological deficit. 4. Extremely high PWP's and induced hypertension are not necessary as routine measures. Acknowledgments The authors thank Drs. J. E. Barnes, J. H. Goodman, T. Hawk, E. J. Kosnik, M. Meagher, and C. Rossel, who had patients included in this study. References 1. Adams HP Jr: Current status of antifibrinolytic therapy for treatment of patients with aneurysmal subarachnoid hemorrhage. Stroke 13:256-259, 1982 2. 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Neurosurgery 13: 394-401, 1983 Manuscript received December 4, 1985. Address reprint requests to: William E. Hunt, M.D., Division of Neurologic Surgery, N-935 Doan Hall, Ohio State University Hospitals, 410 West 10th Avenue, Columbus, Ohio 43210. J. Neurosurg, / Volume 65 / July, 1986