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 »  Abstract
 »  Introduction
 »  Material and methods
 »  Results
 »  Discussion
 »  References

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Year : 2000  |  Volume : 48  |  Issue : 2  |  Page : 126-31

Postoperative hypertensive-hypervolaemic-haemodilution (Triple H) therapy in the treatment of vasospasm following aneurysmal subarachnoid haemorrhage.


Departments of Neurosurgery and Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Correspondence Address:
Departments of Neurosurgery and Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

  »  Abstract

Twenty five patients with post operative ischaemic deficits, following clipping of intracranial aneurysms, were studied. Hypertensive-hypervolaemic-haemodilution (triple H) therapy was given to all patients using colloids and crystalloids. CVP was used to monitor the fluid therapy. Dopamine was needed in 22 patients to elevate the systemic blood pressure. Vasospasm was confirmed in 20 patients with transcranial doppler studies (TCD). 20 (80%) patients survived, 10 (40%) with good outcome, 7 (28%) with fair, 2 (8%) with poor outcome and 1 (4%) with vegetative state. There were 5 (20%) deaths, 4 of which occurred due to infarct. All these patients had poor Hunt and Hess grade at admission, high Fisher grade haemorrhages in the initial CT scan and/or required prolonged temporary clipping at surgery. One death occurred due to central venous line induced septicaemia. The duration of 'triple H therapy' amongst the survivors varied from 2-7 days with an average of 4.6 days. The complications of 'triple H therapy' included hypokalaemia (3 patients), haemorrhagic infarct (1 patient) and septicaemia (1 patient). It is concluded that 'triple H therapy' is useful in treating vasospasm induced ischaemic deficits. It worsens brain oedema in presence of acute infarcts and hence is contraindicated in such patients. A further study involving a larger number of patients with strict haemodynamic and ICP monitoring is suggested to determine the usefulness of individual components of 'triple H therapy'.

How to cite this article:
Gupta D, Sharma B S, Gupta S, Bapuraj R, Khosla V K. Postoperative hypertensive-hypervolaemic-haemodilution (Triple H) therapy in the treatment of vasospasm following aneurysmal subarachnoid haemorrhage. Neurol India 2000;48:126


How to cite this URL:
Gupta D, Sharma B S, Gupta S, Bapuraj R, Khosla V K. Postoperative hypertensive-hypervolaemic-haemodilution (Triple H) therapy in the treatment of vasospasm following aneurysmal subarachnoid haemorrhage. Neurol India [serial online] 2000 [cited 2020 Oct 29];48:126. Available from: https://www.neurologyindia.com/text.asp?2000/48/2/126/1561




   »   Introduction Top

Delayed cerebral ischaemia due to vasospasm is a major cause of death and disability in patients with ruptured intracranial aneurysms. Patients with vasospasm have three times more chances of fatal outcome or disability.[1] The pathogenesis of vasospasm is still incompletely understood. The proposed spasmogens include oxyhaemoglobin, endothelium derived vasoactive peptide endothelin, epinephrine, prostaglandins, serotonin, inflammatory mediators like eicosanoids, cytokines and immune complexes.[2] No agent that specifically antagonises any of the above processes has yet been found. Mechanical clot removal during surgery, fibrinolytic agents like urokinase, tissue plasminogen activator[2] and nimodipine[3],[4] a calcium channel blocker have been shown to improve clinical outcome. Theoretically, any method that would produce a sustained increase in the cerebral blood flow after subarachnoid haemorrhage (SAH) should prevent or alleviate delayed ischaemic deficits and their associated morbidity and mortality.
Elevated systemic blood pressure (BP),[5],[6] intravascular volume expansion[6] and hypertension[7] were thought to increase cerebral blood flow (CBF) and hence the cerebral perfusion pressure.[8] The ischaemic deficits were shown to resolve with this therapy.[9] The regime was soon enthusiastically applied prophylactically against delayed ischaemic deficits in all patients with SAH. However, aggressive use of this therapy led to the recognition of its deleterious effects.[10],[11] A more cautious approach is now advocated. The relative contribution of the components of this therapy to its efficacy are a subject of debate. The haemodynamic indices followed during this therapy have been called arbitrary as is the length of therapy.[12],[13] Although of proven value, the application of this therapy requires further study and a close observation of the patient to determine its indications, limitations and usefulness.
The present study was undertaken with the aim of determination of the usefulness, limitations, complications, optimum duration and the effect of the individual components of 'triple H therapy'.


   »   Material and methods Top

This study was performed on 25 patients who underwent clipping of intracranial aneurysm and showed ischaemic deficits in the post operative period. Thorough general physical and neurological examination was performed and the patients' neurological status was graded according to Hunt and Hess.[14] SAH was confirmed by CT scan. Fisher grading[15] of the subarachnoid blood was done. Digital subtraction cerebral angiography (DSA) was done by transfemoral route in all patients. Baseline measurements of haemoglobin, serum electrolytes, blood sugar and haematocrit were done. After admission, baseline TCD measurement of blood flow velocities in the major intracranial vessels namely internal carotid artery (ICA), middle cerebral artery (MCA) and anterior cerebral artery (ACA) was done. Nimodipine was started orally in all patients in a dose of 60 mg three times a day and continued postoperatively for 3 weeks. Antihypertensives and anticonvulsants were used when indicated. All patients underwent clipping of the aneurysm under general anaesthesia by standard microsurgical techniques, through pterional craniotomy and using Sugita aneurysm clips. Temporary clipping was used when needed and the timing was noted. Mannitol, phenytoin and steroids were given during temporary clipping. Hypotension was generally avoided, except in one patient.
The patients were observed closely during the postoperative period particularly for neurological status. Hourly BP chart was maintained. Daily estimation of haemoglobin, haematocrit, serum electrolytes and arterial blood gases (ABG) was done. Postoperative treatment consisted of antibiotics, steroids, ranitidine, intravenous fluids, phenytoin and analgesics. Any patient who showed neurological deficit, thought to be due to ischaemia from vasospasm, underwent TCD and was put on 'triple H therapy'. A central vein line was inserted through the basilic vein and its correct placement was checked with a chest X-ray. CVP measurement was begun after connecting the central line to a manometer. Normal saline, gelatine (Haemaccel), low molecular weight dextran (Lomodex) and hexaethyl starch (Expan) were infused to increase the CVP to 10-12 cm of saline. If hypervolaemia alone did not improve the patient's condition, the systemic blood pressure was raised by withdrawing antihypertensives, if any, and dopamine infusion was given if required. The dopamine infusion was started at 5 µ g/kg/min and titrated to obtain a systolic BP of 160-180 mmHg. Haematocrit was maintained at 30+3%. Frequent observations of patient's neurological status, BP and CVP were done and the fluid therapy modified as indicated by the clinical status. CT scan was repeated whenever required. The therapy was continued according to the individual patient's response and was gradually withdrawn once the ischaemic neurological deficits disappeared and TCD velocities became normal. The therapy was also withdrawn with the development of brain oedema, infarcts or complications of the therapy.


   »   Results Top

There were 13 males and 12 females. Their ages ranged from 14-65 years with a mean of 41.24 years. 60% patients were in their 4th or 5th decade of life. Their clinical features are depicted in [Table I]. Eight patients were known hypertensive, seven of whom were on irregular treatment. One patient had diabetes. Five patients were in Hunt and Hess grade I and eight in grade II. Six patients each were in Hunt and Hess grade III and IV respectively. Subarachnoid blood on CT was Fisher grade I, II, III and IV in 2, 8, 7 and 8 patients, respectively. One patient with Fisher grade II haemorrhage showed enlarged ventricles in the initial CT. CT appearance and location of aneurysm at angiography is presented in Tables II and III, respectively. Only one of these 25 patients had surgery within the first 48 hours after SAH. In 4 patients, the aneurysms ruptured during surgery and temporary clipping for a total period of 5 to 15 min was required for successful clipping of the aneurysm. Temporary clipping for upto 20 min was used in 5 more patients. Hypotension without temporary clipping was used in only one patient with left ICA bifurcation aneurysm.
Neurological deficits attributed to ischaemia were observed in 11 (44%) patients on the day of surgery, in 8 (32%) patients on the first postoperative day and in 6 (24%) on the second postoperative day. 24 patients had altered sensorium, 11 had hemiparesis and 2 had aphasia. 5 patients had elevated blood flow velocities in MCA and/or ICA in the baseline TCD study recorded before surgery. All of them also showed diffuse vasospasm in the angiogram. Blood flow velocities were normal before surgery in the other 20 patients. Postoperatively, one patient deteriorated rapidly and died before repeat TCD study could be performed. Repeat TCD study was done postoperatively in remaining 24 patients. Blood flow velocities higher than 120 cm/s in MCA and/or ICA were found in 20 patients, confirming vasospasm. Post-operative blood flow velocities were found to be normal in 4 patients. All of them, however, had suffered temporary ischaemia during surgery due to aneurysm rupture and/or temporary clipping and were therefore also given 'triple H therapy'.
All the patients tended to be hypovolaemic immediately after surgery. Their CVP at the start of In this study, 20 (80%) patients survived. Out of these, 10 (40%) had a good outcome, 7 (28%) fair, 2 (8%) poor and 1 (4%) became vegetative. Eight patients had varying degrees of hemiparesis. One patient had aphasia. One patient had both hemiparesis and dysphasia and was improving on follow up. He had developed a right ACA territory infarct postoperatively due to vasospasm. Another patient amongst the survivors had an infarct at presentation and remained hemiplegic. There were 5 (20%) deaths in all. Four of these patients had high clinical and/or high Fisher grade and suffered temporary ischaemia during surgery [Table IV]. The fifth patient who died had improved with 'triple H therapy' after surgery for left ICA bifurcation aneurysm but developed septicaemia and died 6 days later.
The commonest complication of 'triple H therapy' observed in our study was hypokalaemia in 3 patients. Haemorrhagic infarct and septicemia from central line sepsis occurred in one patient each. The duration of 'triple H therapy' in the patients who survived, varied from 2 to 7 days with an average of 4.6 days. Most patients needed it for about 4 days after which it could be gradually withdrawn without worsening of their neurological status. TCD study at this time showed restoration of normal flow velocities in all patients. Three patients required VP shunt insertion for hydrocephalus.



   »   Discussion Top

A high incidence of aneurysms, reported in females in the older age group,[18] was also observed in the present study. Whereas in the western literature, the highest incidence of aneurysmal SAH is in the sixth decade,[18] most patients in this study were in the fourth and fifth decades of life. This finding is consistent with observation made by Rout in his data on Indian patients.[19] Internal carotid and middle cerebral artery aneurysms together outnumbered anterior communicating artery aneurysms, although the latter have a higher statistical incidence. This may be because of selection of patients who showed ischaemic deficits more often in eloquent areas of the brain.
Cerebral blood flow (CBF) across the narrowed arterial segment gets decreased in vasospasm. This decline of CBF, below an ischaemic threshold, may result in delayed ischaemic neurological deficits.[16],[17] Cerebral vasospasm does not always produce cerebral ischaemia or neurological deficits. Ischaemic deficits appear when the vasospasm is severe or associated with hydrocephalus, infection or electrolyte imbalance.[2] Overall incidence of angiographic vasospasm of over 50% is currently accepted.[1] Cerebral infarction may ensue in about 50% of symptomatic cases.[2] Clinically, fever and slight leucocytosis may herald the onset of vasospasm. Later, subtle cognitive changes, confusion, increased headache or meningism may follow. Still later, definite focal signs appear. Many patients in this study had poor clinical grade at presentation which correlates highly with vasospasm risk. These patients tend to have more extensive subarachnoid bleeding. Other risk factors for vasospasm are intraventricular blood, hydrocephalus, hyponatraemia, hypovolaemia, fever, peripheral leucocytosis and antifibrinolytic agents.
TCD is a non invasive technique for detecting vasospasm. Elevated cerebral arterial blood flow velocities correlate highly with angiographic vasospasm.[20] Elevated blood flow velocities in the cerebral vasculature were recorded in 20 patients. 5 of these had angiographic vasospasm which correlated with their ischaemic deficits and were consistent with the findings previously reported.[20] TCD measurement of blood flow velocities was found to correlate with clinical signs of vasospasm in this study. Vasospasm usually begins 3-5 days after SAH, is maximum from 5-14 days and gradually resolves over 2-4 weeks.[21] The critical period appears to be 72 hrs after ictus and removal of the thrombus prior to this time eliminates vasospasm.[1]19 (76%) patients in this study had surgery 3-14 days after the SAH. This corresponds with the acknowledged period of peak vasospasm.[21] On the other hand, there was only one patient who developed vasospasm after early surgery. 5 patients (20%) who had surgery more than 2 weeks after SAH also had vasospasm. In the postoperative period, when the ischaemic deficits appeared, hypovolaemia was noted in all the patients with initial CVP around 5 cm of saline. Although the volume status in this group of patients before surgery was not measured, they were very likely hypovolaemic from the beginning. Poor oral intake,[7] high circulating levels of catecholamines[22] and antinuclear factor (ANF)[23] or other similar factors[24] are considered responsible for the common occurrence of hypovolaemia in such patients. Inotropic support with dopamine was needed in 22 patients, although mere withdrawal of antihypertensive therapy in two patients helped to maintain elevated systemic BP. This has also been reported by Awad et al.[25]
Hypervolaemia was produced by infusion of colloids. Other studies[7],[12],[26],[27] have reported using low molecular weight dextran, blood, plasmanate, albumin and betastarch. In this study, low molecular weight dextran (Lomodex), gelatine (Haemaccel) and hexaethyl starch (Expan) were used and satisfactory volume expansion was obtained. Blood transfusion was avoided if the patient had a haematocrit near 33%. Vasopressor agents such as norepinephrine, phenylephrine, dopamine and dobutamine have been used to elevate systemic blood pressure in the previously reported studies.[7],[12],[25],[26],[27] Dopamine was used as vasopressor agent in 22 patients in this study. The earlier workers[7],[25],[26] used CVP to monitor intravascular volume expansion. They used Swan Ganz catheter only when a high risk of complications related to overhydration was anticipated, such as in patients with cardiac and pulmonary diseases. Such patients were excluded from this study and CVP alone was used. Optimum hypervolaemic therapy was used in this study as described by Shimoda et al.[11]
The overall results of this therapy were quite favourable. 17 out of 25 patients (68%) had a favourable outcome, 2 (8%) had poor outcome and 1 (4%) remained vegetative. There were 5 (20%) deaths out of which 4 occurred in poor grade [Table IV] patients who had intracerebral haematoma and/or intraventricular haematoma in the initial CT. In two patients, the aneurysm ruptured during surgery requiring temporary clip. In the remaining 2 patients temporary clip and hypotension was used before clipping the aneurysm. All these 4 patients developed infarcts inspite of triple H therapy. Probably these patients had suffered ischaemic injury during surgery, which possibly had already advanced to the stage of infarction. These patients did not improve with 'triple H therapy' which had to be withdrawn because of the development of infarcts. One of them developed haemorrhagic infarct leading to rapid neurological deterioration. This therapy is known to worsen brain oedema and produce haemorrhage in preexisting infarcts.[10],[11] In such patients, Oda[28] recommended initial decongestant therapy followed by 'triple H therapy' if needed. Overall, 'triple H therapy' is less effective in these patients, as reported earlier.[25],[27],[29] One patient in this study who died had septicemia although he had responded well to 'triple H therapy' and his ischaemic deficit had improved. The source of sepsis was central venous line infection.
Medlock et al[30] reported a high incidence of pulmonary complications with 'triple H therapy'. They had, however, given hypervolaemia far in excess of the optimum level as determined from the study of Pritz[13] and Levy and Giannotta.[12] Excessive hypervolaemia may account for their high complication rate. No such complication occurred in the present study. Careful monitoring of the fluid therapy is emphasised to prevent fluid overload.
Wood et al[31] have reported a failure of non dilutional hypervolaemia in improving ischaemic deficits. In this study, all the components of hypertension hypervolaemic haemodilutional therapy had been used and they were not employed selectively. Therefore, the relative contribution of these components to the efficacy of the therapy could not be determined. Although 'triple H therapy' showed benefit in many patients with vasospasm, several questions remain unanswered. There exists a need for a further detailed study in a larger number of patients. The proposed study should involve invasive BP measurement, ICP measurement and monitoring of cardiac output and haemodynamic parameters with Swan Ganz catheter to further clarify the role of 'triple H therapy' in vasospasm after aneurysmal SAH especially in the setting of infarcts or brain oedema.

 

  »   References Top

1.Dorsch NWC: Cerebral arterial spasm - a clinical review. Br J Neurosurg 1995; 9: 403-412.   Back to cited text no. 1    
2.Weir B: The pathophysiology of cerebral vasospasm. Br J Neurosurg 1995; 9: 375-390.   Back to cited text no. 2    
3.Allen GS, Ahn HS, Preziosi TJ et al: Cerebral arterial spasm: A controlled trial of nimodipine in patients with subarachnoid haemorrhage. N Engl J Med 1983; 308: 619.   Back to cited text no. 3    
4.Mee E, Dorrance D, Lowe D et al: Controlled study of nimodipine in aneurysm patients treated early after SAH. Neurosurgery 1988; 22: 484.   Back to cited text no. 4    
5.Kassell NF, Peerless SJ, Durward QJ et al: Treatment of ischaemic deficits from vasospasm with intravascular volume expansion and induced arterial hypertension. Neurosurgery 1982; 11: 537-543.   Back to cited text no. 5    
6.Pritz M, Giannotta SL, Kindt GW et al: Treatment of patients with neurological deficits associated with cerebral vasospasm by intravascular volume expansion. Neurosurgery 1978; 3: 364-368.   Back to cited text no. 6    
7.Kosnik EJ, Hunt WE: Postoperative hypertension in the management of patients with intracranial arterial aneurysms. J Neurosurg 1976; 45: 148-154.   Back to cited text no. 7    
8.Waltz A: Effect of blood pressure on blood flow in ischaemic and non-ischaemic cerebral cortex. The phenomenon of autoregulation and luxury perfusion. Neurology 1968; 18: 613-621.   Back to cited text no. 8    
9.Solomon RA, Fink ME, Lennihan L: Early aneurysm surgery and prophylactic hypervolemic hypertensive therapy for the treatment of aneurysmal subarachnoid haemorrhage. Neurosurgery 1988; 23: 699-704.   Back to cited text no. 9    
10.Shimoda M: Complications of hypervolemic therapy. J Neurosurg 1993; 79: 798-801 (letter).   Back to cited text no. 10    
11.Shimoda M, Oda S, Tsugane R et al: Intracranial complications of hypervolemic therapy in patients with delayed ischaemic deficit attributed to vasospasm. J Neurosurg 1993; 78: 423-429.   Back to cited text no. 11    
12.Levy ML, Giannotta SL: Cardiac performance indices during hypervolemic therapy for cerebral vasospasm. J Neurosurg 1991; 75: 27-31.   Back to cited text no. 12    
13.Pritz MB: Treatment of cerebral vasospasm. Surg Neurol 1984; 21: 239-244.   Back to cited text no. 13    
14.Hunt WE, Hess RM: Surgical risk as related to time of intervention in the repair of intracranial aneurysm. J Neurosurg 1968; 28: 14-19.   Back to cited text no. 14    
15.Fisher CM, Kistler JP, Davis JM: Relation of cerebral vasospasm to SAH visualised by CT scanning. Neurosurgery 1980; 6: 1-9.   Back to cited text no. 15    
16.Grubb RL, Raichle ME, Gilling JO et al: Effect of subarachnoid haemorrhage on cerebral blood volume, blood flow and oxygen utilization in humans. J Neurosurg 1977; 46: 446-453.   Back to cited text no. 16    
17.Meyer CHA, Lowe D, Meyer M et al: Progressive changes in cerebral blood flow during the first three weeks after subarachnoid haemorrhage. Neurosurgery 1983; 12: 58-76.   Back to cited text no. 17    
18.Kassell NF, Torner JC, Jane JA et al: The international cooperative study on the timing of aneurysm surgery: Part I: Overall Management results. J Neurosurg 1990; 73: 18-36.   Back to cited text no. 18    
19.Rout D, Krishna Das R: Spontaneous subarachnoid haemorrhage. In: Text Book of Neurosurgery (2nd Ed) Ramamurthi B, Tandon PN (Ed.). BI Churchill Livingstone, New Delhi, 1996; 577.   Back to cited text no. 19    
20.Sekhar LN, Weschsler LR, Yonas H et al: Value of transcranial doppler examination in the diagnosis of cerebral vasospasm after subarachnoid haemorrhage. Neurosurgery 1988; 22: 813-821.   Back to cited text no. 20    
21.Weir B, Grace M, Hansen J et al: Time course of vasospasm in man. J Neurosurg 1978; 8: 173-178.   Back to cited text no. 21    
22.Nelson RJ, Roberts J, Rubin C et al: Association of hypovolaemia after subarachnoid haemorrhage with computed tomographic scan evidence of raised intracranial pressure. Neurosurgery 1991; 29: 178-182.   Back to cited text no. 22    
23.Diringer M, Ladenson PW, Stern BJ et al: Plasma atrial natriuretic factor and subarachnoid haemorrhage. Stroke 1988; 19: 1119-1123.   Back to cited text no. 23    
24.Okuchi K, Fujioka M, Fujikawa A et al: Rapid natriuresis and preventive hypervolaemia for symptomatic vasospasm after subarachnoid haemorrhage. Acta Neurochir 1996; 138: 951-957.   Back to cited text no. 24    
25.Awad IA, Carter P, Spetzler RF et al: Clinical vasospasm after subarachnoid haemorrhage: Response to hypervolaemic haemodilution and arterial hypertension. Stroke 1987; 18(2): 365-372.   Back to cited text no. 25    
26.Muizelaar JP, Becker DP: Induced hypertension for the treatment of cerebral ischaemia after subarachnoid haemorrhage. Surg Neurol 1986; 25: 317-325.   Back to cited text no. 26    
27.Origitano TC, Wascher TM, Reichman OH et al: Sustained increased cerebral blood flow with prophylactic hypertensive hypervolemic haemodilution ('Triple H therapy') after subarachnoid haemorrhage. Neurosurgery 1990; 27: 729-740.   Back to cited text no. 27    
28.Oda S, Shimoda M, Sato O: Early aneurusym surgery and dehydration therapy in patients with severe subarachnoid haemorrhage without ICH. Acta Neurochir 1996; 138: 1050-1056.   Back to cited text no. 28    
29.Gumprecht H, Winkler R, Gerstner W et al: Therapeutic management of grade IV aneurysm patients. Surg Neurol 1997; 47: 54-59.   Back to cited text no. 29    
30.Medlock MD, Dulebohn SC, Elwood PW: Prophylactic hypervolemia without calcium channel blockers in early aneurysm surgery. Neurosurgery 1992; 30: 12-16.   Back to cited text no. 30    
31.Wood JH, Snyder LL, Simeone FA: Failure of intravascular volume expansion without haemodilution to elevate cortical blood flow in region of experimental focal ischaemia. J Neurosurg 1982; 56: 80-91.   Back to cited text no. 31    

 

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