Treatment of intraoperative hypertensive emergencies in patients with intracranial disease

In patients with neuropathologic processes leading to disturbed cerebrovascular autoregulation, sudden increases in arterial blood pressure may lead to a sudden elevation in cerebral blood flow and intracranial pressure. Therefore, sudden increases in arterial pressure should be assiduously avoided in the perioperative period. Hypertensive episodes may occur at any time during anesthesia, but are more likely to occur (1) during laryngoscopy and intubation, (2) at the time of skin incision, (3) at extubation, and (4) during awakening. In patients with cardiovascular disease, such hypertensive episodes may also cause deterioration of the cardiovascular situation. Catecholamines are the principal mediators of such intraoperative hypertensive reactions. There are 2 options available to the anesthesiologist: (1) attempt to suppress this response after it has occurred, or (2) prevent its occurrence at the outset. Treatment of hypertension often relies on agents that relax vascular smooth muscle. In patients with compromised intracranial compliance, however, cerebral vasodilation must be avoided because it leads to an increase in cerebral blood volume. This, in turn, may raise intracranial pressure and result either in herniation of brain contents or a decrease in cerebral perfusion pressure leading to brain ischemia. Different pharmacologic means of preventing or suppressing such intraoperative hypertensive reactions are reviewed. Many of the drugs reviewed resulted in adverse effects that could preclude their use in patients with reduced intracranial compliance. Alpha- and beta-adrenergic receptor blockers can safely be administered to such patients.     

Blood pressure control in acute cerebrovascular disease

Acute cerebrovascular diseases (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) affect 780,000 Americans each year. Physicians who care for patients with these conditions must be able to recognize when acute hypertension requires treatment and should understand the principles of cerebral autoregulation and perfusion. Physicians should also be familiar with the various pharmacologic agents used in the treatment of cerebrovascular emergencies. Acute ischemic stroke frequently presents with hypertension, but the systemic blood pressure should not be treated unless the systolic pressure exceeds 220 mm Hg or the diastolic pressure exceeds 120 mm Hg. Overly aggressive treatment of hypertension can compromise collateral perfusion of the ischemic penumbra. Hypertension associated with intracerebral hemorrhage can be treated more aggressively to minimize hematoma expansion during the first 3 to 6 hours of illness. Subarachnoid hemorrhage is usually due to aneurysmal rupture; systolic blood pressure should be kept <150 mm Hg to prevent re-rupture of the aneurysm. Nicardipine and labetalol are recommended for rapidly treating hypertension during cerebrovascular emergencies. Sodium nitroprusside is not recommended due to its adverse effects on cerebral autoregulation and intracranial pressure. Hypoperfusion of the injured brain should be avoided at all costs.     

降血压治疗对脑血流动力学影响的初步研究

目的 :探讨降血压治疗是否影响脑血流动力学。方法 :应用经颅多普勒超声 (TCD)诊断仪监测原发性高血压患者 32例以硝苯地平及 17例以硝苯地平 +卡托普利降血压前后的脑血流参数 ,以及 11例血压大于 2 0 0 / 130mmHg的脑出血患者不同梯度地降血压前后的TCD血流参数的变化。结果 :三组药物降血压效果均有显著性意义。高血压患者双侧大脑中动脉血流速度 (MFV)降低无统计学意义 ,PI值升高有统计学意义 ;脑出血患者不同梯度降血压健侧和患侧MFV降低、PI升高 ,均有统计学意义 ,而两组药物之间TCD参数差异无统计学意义。结论 :原发性高血压患者脑血管仍有一定的调节功能 ,脑出血患者降血压治疗可能会更降低脑灌注压 ,应慎重应用降压药。     

Effects of rapid blood pressure reduction on cerebral blood flow

The changes that occur in the cerebral circulation with chronic hypertension are important when considering the therapeutic possibilities in treating patients with severe hypertension. Care must be taken not to lower the blood pressure below the lower limit of autoregulation, no matter what drug is used. In patients with severe, chronic hypertension, blood pressure should be lowered carefully. Rapid blood pressure reduction to a level that is below the lower limit of autoregulation may result in central nervous system dysfunction due to cerebral hypoperfusion. This is especially true in patients with increased intracranial pressure and cerebral edema such as those with hypertensive encephalopathy.     

Management of hypertension in patients with acute stroke

Lowering systemic blood pressure (BP) in patients with acute cerebral infarction may produce clinical deterioration. Because of impaired cerebral autoregulation and the spontaneous fluctuations in BP following stroke, antihypertensive medication should be avoided in patients with acute cerebral infarction unless vital organs such as the heart or kidney are compromised, the diastolic BP rises to 130 mm Hg or greater, or the patient has hypertensive encephalopathy. Brief remarks about BP control in intracerebral hematoma and subarachnoid hemorrhage are also included.     

Blutdruck und Gehirn

During acute cerebral infarction, autoregulation is abolished. Brain perfusion therefore directly depends on perfusion pressure and cardiac output. For this reason, in the early state of stroke, elevated blood pressure improves cerebral blood flow and only values of 210 mmHg systolic or above should be lowered. With the development of a vasogenic brain edema or a dysfunctional blood-brain barrier (usually on day 2 to 4 after infarction), blood pressure must be normalized in order to avoid hemorrhage and to minimize edema. In the presence of space occupying edema or intracranial hemorrhage, only those antihypertensive substances may be used which do not cause a dilatation of brain vessels. Direct vasodilators and calcium antagonists are not suitable in this situation. Furthermore, antihypertensive medication which causes bradycardia (e.g. beta blockers) should be avoided, because in acute stroke, brain perfusion also depends on the cardiac output.For primary and secondary stroke prevention normalization of blood pressure is essential. Efficacy is basically independent of the kind of antihypertensive medication used. Effective normalization of blood pressure probably helps to prevent vascular dementias of all kinds. Convincing studies however are still lacking for most sorts of antihypertensive medication.     

Altered circadian rhythm of blood pressure and cerebrovascular damage

An abnormal circadian rhythm of blood pressure [i.e. a lesser or 'reverse' nocturnal fall of blood pressure (nondippers)] is associated with cerebrovascular damage including intracranial hemorrhaging, thrombosis, and vascular dementia. Silent cerebrovascular damage such as lacunae and periventricular hyperintensity lesions is not infrequently detected in apparently healthy hypertensive elderly subjects by brain magnetic resonance imaging and also is more common among nondippers than it is among dippers. Although no exact cause-effect relationship is known, a decrease in nocturnal fall of blood pressure might be secondary to a site-specific injury to the brain resulting in an impairment of central autonomic nervous system functioning. Besides nondipping, evidence suggests that the extreme dipping (a marked nocturnal fall of blood pressure) should be considered a type of abnormal diurnal blood pressure variation in elderly patients with hypertension who are likely to have advanced silent cerebrovascular damage. The pathogenic significance of 'extreme dipping' might be an 'artificial' excess reduction in blood pressure at night beyond the lower limit of blood pressure in the autoregulation of cerebral blood flow that is probably induced by antihypertensive agents. It is also possible that a greater blood pressure variability in extreme dippers itself accelerates the hypertensive target-organ damage. Prospective follow-up of subjects with these distinct subtypes of abnormal circadian blood pressure variation as well as trials comparing a group of treated patients with various degrees of dipping with a group of untreated counterparts may establish the validity of assessing these distinct circadian rhythms of blood pressure as a useful clinical parameter in the management of hypertension.     

Hypertension in the intensive care unit

PURPOSE OF REVIEW: The severity of hypertensive crises is determined by the presence of target organ damage rather than the level of blood pressure. Hypertensive urgencies with no signs of organ dysfunction can therefore be distinguished from hypertensive emergencies in which the presence of severe end-organ damage requires prompt therapy. Hypertensive emergencies include acute aortic dissection, hypertensive encephalopathy, acute myocardial ischaemia, severe pulmonary oedema, eclampsia, and acute renal failure. RECENT DEVELOPMENTS: Malignant hypertension is a severe form of hypertensive emergency demanding special consideration because of the risks of permanent blindness and renal failure. Catecholamine excess and postoperative hypertension may also sometimes require urgent treatment. The management of patients with hypertensive emergencies must be ensured in an intensive care unit, and must include the parenteral administration of antihypertensive drugs and accurate blood pressure monitoring. SUMMARY: Except for acute aortic dissection, the recommended goals of treatment are a reduction of mean arterial pressure by no more than 20% during the first few hours, because an abrupt fall in blood pressure in patients with preexisting hypertension may induce severe ischaemic injury in major organs as a result of the chronic adaptation of autoregulation mechanisms. Hypertension in the context of acute stroke should be treated only rarely and cautiously because of the presence of impaired autoregulation.     

Arterial hypertension in neurosurgical emergencies

The Cushing, or ischemic response, is a useful mechanism in intracranial hypertension because it restores normal cerebral perfusion pressure and cerebral circulation. In patients with acute intracranial hypertension due to mass-expanding lesions such as brain edema, hydrocephalus or brain tumor, cerebral perfusion pressure decreases and plateau waves occur. In experimental animals, spontaneous or induced arterial hypertension can compensate for the reduction of cerebral perfusion pressure. The interrelation between arterial pressure, intracranial pressure and cerebral perfusion pressure in an experimental model of hydrocephalus in dogs was investigated. Plateau waves were preceded by a decrease in cerebral perfusion pressure and a Cushing response was seen 5 to 15 seconds before abolition of the wave. Arterial hypertension, induced by intravenous infusion of Aramin, restored cerebral perfusion pressure and intracranial pressure became normal. Arterial hypertension appears to be an efficient stimulus to abort plateau waves. Hypertensive patients in whom subarachnoid bleeding develops from ruptured aneurysm are at high risk of bleeding again and need antihypertensive treatment together with drainage of cerebrospinal fluid. Induced arterial hypertension is the most effective treatment of vasospasm but increases the danger of aneurysmal rebleeding and can only be safe after clipping of the aneurysm. This is one of the strongest arguments for early operation on cerebral aneurysms.     

Morphologic changes during hypertension

Circulation to the brain is greatly affected by hypertension and by its treatment. Neurologic dysfunction is prominent among the complications of increased arterial pressure and is also most susceptible to preventive antihypertensive therapy. The upward resetting of the limits of autoregulation of cerebral blood flow in hypertension is probably due largely to structural thickening of the walls (hyaline arteriosclerosis) of the resistance vessels. Other consequences of hypertensive vascular lesions in the brain include increased formation of atheroma, lacunae and lacunar infarction, cerebral infarction, multi-infarct dementia and Binswanger's disease. There is also an association between hypertension and hemorrhagic strokes, namely, subarachnoid and intracerebral hemorrhage. Brain lesions are also prominent in malignant hypertension and hypertensive encephalopathy. Antihypertensive treatment, especially if intensive, can result in boundary zone ischemia in the brain if arterial pressure decreases steeply.     

Cerebral hemodynamics after short- and long-term reduction in blood pressure in mild and moderate hypertension

This study tested the hypothesis that acute reduction in blood pressure (BP) at the initial stage of antihypertensive therapy compromises brain perfusion and dynamic cerebral autoregulation in patients with hypertension. Cerebral blood flow velocity and BP were measured in patients with mild and moderate hypertension and in healthy volunteers at baseline upon reduction of BP within 1 to 2 weeks of administration of losartan/hydrochlorothiazide and after 3 to 4 months of treatment. The transfer function between beat-to-beat changes in BP and cerebral blood flow velocity was estimated to assess dynamic autoregulation. After 1 to 2 weeks of treatment, BP was reduced in mild (143+/-7/88+/-4 versus 126+/-12/77+/-6 mm Hg) and moderate hypertension (163+/-11/101+/-9 versus 134+/-17/84+/-9 mm Hg; P<0.05). These reductions in BP were well maintained over the 3 to 4 month period. Cerebral blood flow velocity did not change, whereas cerebrovascular resistance index was reduced by 17% (P<0.05) after reduction in BP. Responses of cerebral blood flow velocity to head-up tilt remained unchanged. Baseline transfer function gain at the low frequencies (0.07 to 0.20 Hz) was reduced in moderate hypertension, consistent with cerebral vasoconstriction and/or enhanced dynamic autoregulation. However, this reduced transfer function gain was restored to the level of control subjects after reduction in BP. These findings, contrary to our hypothesis, demonstrate that there is a rapid adaptation of the cerebral vasculature to protect the brain from hypoperfusion even at the initial stage of antihypertensive therapy in patients with mild and moderate hypertension.     

Antihypertensive therapy increases cerebral blood flow and carotid distensibility in hypertensive elderly subjects

Many physicians are reluctant to lower blood pressure to recommended levels in elderly hypertensive patients because of concern about producing cerebral hypoperfusion. Because hypertension is associated with potentially reversible structural and functional alterations in the cerebral circulation that may improve with treatment, we investigated whether long-term pharmacological reduction of systolic blood pressure will improve, rather than worsen, cerebral blood flow and its regulation. Three groups of elderly subjects 65 years of age or older were studied prospectively: normotensive subjects (N=19), treated hypertensive subjects with systolic pressure <140 mm Hg (N=18), and uncontrolled hypertensive subjects with systolic pressure >160 mm Hg at entry into the study (N=14). We measured beat-to-beat blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography), finger arterial pressure (photoplethysmography), and pulsatile distensibility of the carotid artery (duplex Doppler ultrasonography) at baseline and after 6 months of observation or antihypertensive therapy. After baseline hemodynamic measurements, uncontrolled hypertensive subjects underwent aggressive treatment with lisinopril with or without hydroclorothiazide or, if not tolerated, nifedipine or an angiotensin receptor blocker to bring their systolic pressure <140 mm Hg for 6 months. The other 2 groups were observed for 6 months. After 6 months of successful treatment, uncontrolled hypertensive subjects had significant increases in cerebral blood flow velocity and carotid distensibility that was not seen in the other groups. Treatment reduced cerebrovascular resistance and did not impair cerebral autoregulation. Therefore, judicious long-term treatment of systolic hypertension in otherwise healthy elderly subjects does not cause cerebral hypoperfusion.     

Why Do Treated Hypertensives Suffer Strokes? An Internist's Perspective

Despite widespread treatment of hypertension, stroke continues to be the third leading cause of death in the United States. Antihypertensive therapy is more effective in preventing hemorrhagic strokes than ischemic strokes. In order to understand the reasons why antihypertensive therapy is only partially successful in the eradication of ischemic strokes, differences in the pathogenesis and treatment of subtypes of stroke must be considered. There are three main stroke subtypes of ischemic strokes: small-vessel arteriopathic (lacunar), large-artery atherothrombotic, and cardioembolic. Hypertension is the major cause of lacunar strokes but plays a lesser role in the pathogenesis of atherothrombotic strokes. Antihypertensive therapy prevents the majority of lacunar strokes but may not have a major impact on the occurrence of atherothrombotic strokes. Due to impaired cerebral autoregulation, overtreatment of hypertension, especially in the elderly and in patients with previous strokes, may paradoxically lead to stroke (J-curve). Assuming that the majority of lacunar strokes are prevented by judicious antihypertensive therapy, future therapeutic efforts should concentrate on the prevention of atherothrombotic and cardioembolic strokes. In this regard, refinement of surgical techniques, pharmacologic approaches aimed at plaque stabilization, and the application of transesophageal echocardiography for the diagnosis of embolic strokes (and anticoagulation for a probable source) are promising. Besides the obvious reasons of noncompliance and inadequate therapy, overly aggressive treatment of hypertension in the elderly and stroke mechanisms unrelated to blood pressure may explain the occurrence of strokes despite our efforts to treat hypertension.     

Why Do Treated Hypertensives Suffer Strokes? An Internist's Perspective

Despite widespread treatment of hypertension, stroke continues to be the third leading cause of death in the United States. Antihypertensive therapy is more effective in preventing hemorrhagic strokes than ischemic strokes. In order to understand the reasons why antihypertensive therapy is only partially successful in the eradication of ischemic strokes, differences in the pathogenesis and treatment of subtypes of stroke must be considered. There are three main stroke subtypes of ischemic strokes: small-vessel arteriopathic (lacunar), large-artery atherothrombotic, and cardioembolic. Hypertension is the major cause of lacunar strokes but plays a lesser role in the pathogenesis of atherothrombotic strokes. Antihypertensive therapy prevents the majority of lacunar strokes but may not have a major impact on the occurrence of atherothrombotic strokes. Due to impaired cerebral autoregulation, overtreatment of hypertension, especially in the elderly and in patients with previous strokes, may paradoxically lead to stroke (J-curve). Assuming that the majority of lacunar strokes are prevented by judicious antihypertensive therapy, future therapeutic efforts should concentrate on the prevention of atherothrombotic and cardioembolic strokes. In this regard, refinement of surgical techniques, pharmacologic approaches aimed at plaque stabilization, and the application of transesophageal echocardiography for the diagnosis of embolic strokes (and anticoagulation for a probable source) are promising. Besides the obvious reasons of noncompliance and inadequate therapy, overly aggressive treatment of hypertension in the elderly and stroke mechanisms unrelated to blood pressure may explain the occurrence of strokes despite our efforts to treat hypertension.     

Cerebrovascular aspects of antihypertensive treatment

Although the treatment of hypertension clearly benefits the brain in most patients, there are, however, unfortunate exceptions. Overzealous blood pressure lowering especially, and sometimes conservative blood pressure lowering, occasionally compromise the supply of blood to the brain to such an extent that neurological dysfunction or death results. Despite an awareness of this problem for more than a decade, the number of reports of such cases is increasing. An understanding of the problem requires detailed knowledge of both the pathophysiology of the cerebral circulation in hypertension and the cerebrovascular effects of antihypertensive drugs. If antihypertensive treatment, in particular emergency blood pressure lowering, is to always be safe, thought must be given to the cerebrovascular effects of the drugs to be used. This topic is discussed in relation to the observed (i.e., experimentally determined) and inferred (i.e., from clinical observation) effects of antihypertensive drugs and treatment on the cerebral circulation, especially with regard to autoregulation of cerebral blood flow.     

A new cause of resistant arterial hypertension: coprescription with anticonvulsant treatments]

This article provides two case reports about pharmacokinetic interactions with hypertensive drug therapy and anticonvulsive treatment. First, a 49-year-old patient presenting severe hypertension had a non-traumatic cerebral hemorrhage with convulsions. Extensive etiologic investigations did not find any cause of secondary hypertension. Under an association of four antihypertensive drugs regimen, associated with carbamazepine blood pressure was not controlled. Finally, blood pressure was well controlled after replacement of carbamazepine with vigabatrin. The second case reports a 64-year-old treatment-resistant essential hypertensive patient, carbamazepine was associated with antihypertensive treatment because of aggressivity attributed to Alzheimer's disease. After withdrawal of carbamazepine treatment, blood pressure reached normal values with the same antihypertensive regimen. Those case reports suggest drug-drug interactions between antihypertensive and anticonvulsive drug therapies. Following explanation can be hypothesis: several antihypertensive drugs are liver-metabolised by microsomal cytochrome P450 3A4 isoform that could explain a significantly decreased half-life in association with enzymatic inducers, such as rifampicine or antiepileptic drugs (phenobarbital, phenytoin or carbamazepine). CONCLUSION: When blood pressure is not controlled without cause of secondary hypertension, physicians must be careful with drug-drug interactions.     

Cerebral autoregulation and acute ischemic stroke

Cerebral autoregulation tightly controls blood flow to the brain by coupling cerebral metabolic demand to cerebral perfusion. In the setting of acute brain injury, such as that caused by ischemic stroke, the continued precise control of cerebral blood flow (CBF) is vital to prevent further injury. Chronic as well as acute elevations in blood pressure are frequently associated with stroke, therefore, understanding the physiological response of the brain to the treatment of hypertension is clinically important. Physiological data obtained in patients with acute ischemic stroke provide no clear evidence that there are alterations in the intrinsic autoregulatory capacity of cerebral blood vessels, except perhaps in infarcted tissue. While it is likely safe to modestly reduce blood pressure by 10-15 mm Hg in most patients with acute ischemic stroke, to date, there are no controlled trial data to indicate that reducing blood pressure is beneficial. There may be subgroups, such as those with persistent large vessel occlusion, large infarcts with edema causing increased intracranial pressure or local mass effect, or chronic hypertension, in which blood pressure reduction may lead to impaired cerebral perfusion in noninfarcted tissue.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.53.     

Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, restores the lower limit of autoregulation of cerebral blood flow in the awake renovascular hypertensive rat

Chronic hypertension shifts the lower limit of cerebral blood flow autoregulation to a higher pressure level. Although acute administration of angiotensin converting enzyme inhibitors restores the lower limit of cerebral blood flow autoregulation the chronic effects have not received much attention. We studied the effect of the angiotensin converting enzyme inhibitor, perindopril, on mean arterial pressure, basal cerebral blood flow and cerebral blood flow autoregulation in renovascular hypertensive (two-kidney, one clip model) and normotensive male Wistar rats. Seven weeks after renal artery clipping or sham operation rats received daily intraperitoneal injections of perindopril. The dose was increased from 1 to 8 mg/kg over the first 4 weeks until blood pressure was normalized. Chronic renovascular hypertension caused a marked shift in the lower limit of cerebral blood flow autoregulation but did not alter basal cerebral blood flow. Treatment of hypertensive rats with perindopril normalized blood pressure and restored cerebral blood flow autoregulation. Chronic treatment of normotensive rats with perindopril increased basal cerebral blood flow. In conclusion, chronic treatment of renovascular hypertensive rats with perindopril causes a shift in the lower limit of cerebral blood flow autoregulation towards the value observed in normotensive rats.     

Comprehensive management of hypertensive emergencies and urgencies

Despite advances in chronic hypertension management, hypertensive emergencies and urgencies remain as serious complications. Much of this relates to poor compliance with effective antihypertensive management. Hypertensive emergencies and urgencies can also be seen as the initial manifestations of hypertension in pregnancy and in the perioperative period. Multiple classes of intravenous antihypertensive drugs are available to treat hypertensive emergencies, and specific agents may have an advantage in a given clinical situation. Orally active agents are used to treat hypertensive urgencies, and include clonidine, angiotensin-converting enzyme inhibitors, and labetalol. Most patients respond to drug therapy, but problems may arise related to a rapid normalization of blood pressure.     

脑出血患者的血压调控以及经颅多普勒监测的临床意义

目的:研究高血压性脑出血患者的血压调整幅度与应用经颅多普勒(TCD)监测脑血流动力学改变的临床指导意义。方法:动态监测64例发病后10h内入院的脑出血患者的血压,其中38例入院24h内行颅内血肿穿刺和置管引流术(手术组),18例患者行保守治疗(保守组),患者于入院当时以及第1、4、7天和2周时进行TCD监测;另外8例未手术者(降压组)在接受抗高血压治疗前、后行TCD监测,并与26例单纯高血压患者(对照组)抗高血压治疗前、后的TCD参数进行比较。结果:对照组抗高血压治疗前、后的TCD参数无显著差异,而降压组降压后双侧大脑中动脉(MCA)流速降低,搏动指数(PI)升高。脑出血患者治疗过程中血压逐渐下降,双侧MCA流速呈先降后升,双侧PI值呈先升后降趋势。保守组的MCA流速在发病1周内下降,第2周开始升高,PI值改变与其相反;手术组第7天MCA流速即升高,PI值降低,且在第14天两组间有显著差异;手术组血压下降幅度较保守组大,第14天时两组间的收缩压有显著差异。结论:颅内血肿穿刺和置管引流术可显著改善脑出血患者的脑灌注程度,而急性期抗高血压治疗不利于脑灌注,动态TCD监测可评价患者脑灌注状态和指导临床治疗。