1.Concept and classification
Hypertensive emergencies are a common clinical phenomenon in the emergency department and all departments, and are a life-threatening emergency. It is clinically divided into hypertensive emergencies and hypertensive sub-emergencies. Hypertensive emergencies refer to a serious life-threatening clinical syndrome in patients with primary or secondary hypertension, in which blood pressure suddenly and significantly increases (generally SBP exceeds 180 mmHg, DBP exceeds 120 mmHg) under the action of certain triggers, accompanied by progressive acute impairment of the function of important target organs such as heart, brain and kidney. Subacute hypertension refers to a significant increase in blood pressure without target organ damage. The two together are called hypertensive crisis.
2.Pathophysiological mechanism
The mechanism of hypertensive emergencies is still poorly understood. It is believed that the systemic vascular resistance and the uncontrolled self-regulation of cerebral blood flow are involved in the occurrence of hypertensive crisis, while the endothelial and coagulation damage caused by inflammation is the core mechanism. When blood pressure rises sharply, it leads to a rightward shift of the self-regulation curve, causing high mean arterial pressure and increased cerebral blood flow. Therefore, in order to avoid tissue hyperperfusion, blood pressure must be lowered rapidly and effectively, but at the same time, according to the patient’s condition, blood pressure must be lowered carefully to avoid the possibility of ensuing hypoperfusion.
3. Treatment principles and antihypertensive targets for hypertensive emergencies
The basic principles of antihypertensive treatment for hypertensive emergencies are.
(1) Rapidly lower blood pressure: usually requires intravenous infusion pump or intravenous drip administration. The advantage of intravenous drip administration is that the dose of the drug administered is flexibly adjusted according to the changing characteristics of blood pressure. If the situation permits, early initiation of oral antihypertensive drug therapy.
(2) Controlled blood pressure lowering: To avoid a significant reduction in blood perfusion to vital organs due to rapid blood pressure lowering, gradual controlled blood pressure lowering should be adopted.
(3) Rational selection of antihypertensive drugs: choose drugs with rapid onset of action, short duration of action, faster disappearance of action after discontinuation, less adverse effects, and less impact on cardiac and cerebral blood flow.
The ultimate goal of antihypertensive is to protect organ function, reduce complications and improve patient prognosis. An individualized treatment plan is developed according to the condition, and blood pressure is lowered in a rhythmic and targeted manner. It is important to bring the blood pressure down rapidly to a safe level to prevent progressive or irreversible target organ damage, but not to bring it down too fast or excessively, otherwise it will cause inadequate perfusion of local or systemic tissues and organs. After stabilization of hypertensive emergencies, the causes or triggers of abnormally high blood pressure are corrected to prevent recurrence. However, all current recommendations are derived from expert experience and there are no data from randomized controlled studies to determine how to individualize treatment.
The goals of blood pressure lowering in hypertensive emergencies are divided according to timing.
First goal: The first goal of antihypertensive treatment for hypertensive emergencies is to lower blood pressure to a safe level in 30-60 min. This safety level must be determined on a patient-by-patient basis due to the varying levels of basal blood pressure and the combined target organ damage. Except in special cases (ischemic stroke, aortic coarctation), it is recommended that the mean arterial pressure (MAP) be rapidly reduced to no more than 20%-25% of the basal blood pressure and the diastolic blood pressure (DBP) to 100-110 mmHg or no more than 25% of the basal blood pressure within the first 1-2H. The critical nature of the self-regulation of blood pressure needs to be fully recognized during emergency antihypertensive treatment. If the blood pressure is sharply reduced by treatment, narrowing the space for self-regulation of the vascular bed can lead to inadequate tissue perfusion and/or infarction.
Second goal: to lower the blood pressure to the target value, usually 160/(100-110) mmHg, in the subsequent 2 to 6H, with the specific target value adjusted appropriately according to the patient’s condition. After the first goal is reached, the rate of blood pressure lowering should be slowed down, oral antihypertensive drugs should be added, and the rate of intravenous drug administration should be gradually slowed down to gradually lower the blood pressure to the second goal.
Third target: If the blood pressure level of the second target is tolerable and the clinical condition is stable, gradually lower the blood pressure to normal level in the following 24-48H. Different combined target organ damage of blood pressure reduction target.
4.Treatment principles and antihypertensive targets for subacute hypertension
For patients with subacute hypertension, too rapid a decrease in blood pressure is more likely to be accompanied by serious neurological complications, and too rapid correction of blood pressure beyond the automatic regulation range of the vascular bed can lead to reduced perfusion of important tissues and organs such as the kidney, brain and coronary arteries, resulting in tissue ischemia and infarction. Therefore, injectable antihypertensive drugs and oral rapid-acting antihypertensive drugs are not recommended for use in subacute patients without target organ damage.
The antihypertensive strategy for patients with subacute hypertension is to use oral antihypertensive agents, usually without hospitalization, with blood pressure monitoring, to lower blood pressure smoothly over 24 h to several days is recommended. Although there is a lack of sufficient evidence to suggest the optimal timing and type of drug selection for blood pressure lowering, there is evidence that sublingual nifedipine tablets can lead to reduced blood flow to the brain, heart and kidneys, so they are not recommended for patients with critical hypertension, including subacute hypertension.
5.Commonly used antihypertensive drugs and classification
5.1 Precautions
(1) Rapid and appropriate lowering of blood pressure, and removal of the causes of acute illness;
(2) The effect of extra-venous drugs is slow and not easy to adjust, usually need to be given intravenously;
(3) Strengthen general treatment: oxygen, bed rest, psychological care, quiet environment, monitoring vital signs, maintaining water and electrolyte balance, and preventing and treating complications;
(4) Drugs to be avoided: It should be noted that some antihypertensive drugs are inappropriate for acute hypertension and even harmful. Powerful diuretic antihypertensive drugs should not be used at the beginning of treatment unless there is heart failure or obvious overload of body fluid volume, because in most hypertension the sympathetic nervous system and renin-angiotensin-aldosterone system (RAAS) are over-activated, peripheral vascular resistance is significantly increased, and the circulating blood volume in the patient’s body is reduced, and powerful diuresis is dangerous.
5.2 Drug classification
This paper only introduces the pharmacological properties and use of some commonly used antihypertensive drugs in China.
5.2.1 Vasodilators
(1) sodium nitroprusside: sodium nitroprusside is a direct vasodilator, which can directly dilate both arteries and veins, especially coronary arteries, reduce the pre and afterload of the heart, reduce left ventricular volume, reduce ventricular wall pressure, increase the output per beat and reduce myocardial oxygen consumption. The drug has a short half-life and is easy to adjust, and can be used in various hypertensive emergencies.
The initial dose is 0.5μg/(kg-min), and the dose is gradually increased by 0.5μg/(kg-min) according to the efficacy, usually the maintenance dose is 3μg/(kg-min), and the extreme dose is 10μg/(kg-min). If the extreme dose has been reached and the effect of lowering blood pressure is still unsatisfactory after 10 min, discontinuation of the drug should be considered. In the usual dose of mild adverse reactions, nausea, vomiting, muscle tremors, toxic reactions are mainly caused by cyanide poisoning, drip site such as drug extravasation can cause local skin and tissue reactions.
(2) nitrate preparations: commonly used nitroglycerin or isosorbide nitrate. It mainly dilates peripheral veins, and also has the effect of dilating peripheral small arteries and coronary arteries. The effect of intravenous drip is immediate, and disappears a few minutes after stopping the drug.
It is mainly used in acute hypertension with acute pulmonary edema and acute coronary syndrome. It is contraindicated in patients with intracranial hypertension, glaucoma, hypertrophic obstructive cardiomyopathy, cerebral hemorrhage or cranial trauma. Common adverse reactions include headache, dizziness, skin flushing, etc.
5.2.2 Calcium channel antagonists
(1) Nicardipine: Nicardipine is a potent, water-soluble dihydropyridine calcium channel antagonist with antihypertensive effectiveness similar to that of sodium nitroprusside, mainly dilating small and medium-sized arteries and reducing cardiac afterload, with little effect on veins. It has a high degree of vascular selectivity, the selectivity of vertebral artery, coronary artery and terminal small artery is much higher than that of myocardium, no obvious negative inotropic effect, while lowering blood pressure can improve blood flow to heart, brain and other organs, and has a protective effect on ischemic myocardium.
It is suitable for short-term emergency treatment of hypertensive emergencies and abnormal hypertension during surgery, especially for patients with acute hypertension with insufficient basilar artery blood supply, insufficient coronary artery blood supply or mitral valve closure insufficiency and low cardiac output with moderately elevated terminal resistance and pulmonary artery pressure. This drug has a moderate diuretic effect and does not affect gas exchange in the lungs. The half-life of nicardipine is medium, with an intravenous onset of action of 5-10 min and a duration of 1-4 h. The process of blood pressure control is smooth, not easy to cause excessive reduction of blood pressure, not easy to rebound after discontinuation of the drug, no significant resistance, but does not change the circadian rhythm of blood pressure. Forbidden to use in severe aortic stenosis.
(2) Diltiazem: Diltiazem is a non-dihydropyridine calcium channel antagonist, which can relax vascular smooth muscle and reduce peripheral vascular resistance so as to lower blood pressure, as well as improve coronary blood flow and reduce autoregulation and conduction of sinus node and atrioventricular node, and control rapid supraventricular arrhythmias. It is mainly used for hypertensive crisis or acute coronary syndrome, usually at the rate of 5-15μg/(kg-min) per hour intravenously, and the rate is adjusted according to the change of blood pressure. Its adverse effects include bradycardia, edema, headache, rash, etc. It is contraindicated in patients with pathological sinus node syndrome, atrioventricular block of second degree or higher, and severe congestive heart failure. Long-term intravenous administration is contraindicated due to its cardiac depressant effect.
5.2.3 Peripheral alpha-blockers
(1) Uraldial: Uraldial has a dual effect of peripheral alpha blockade and central regulation of blood pressure. It has the advantages of reducing cardiac load, lowering myocardial oxygen consumption, increasing cardiac stroke volume, lowering pulmonary hypertension and increasing renal blood flow, and does not increase intracranial pressure. Therefore, it is suitable for most hypertensive emergencies (most hypertensive emergencies have varying degrees of sympathetic hyperactivity) and is effective for hypertensive crisis caused by pheochromocytoma.
Treatment of hypertensive emergencies can be 12.5mg diluted intravenous injection, usually within 5min onset of effect, after 10-15min effect is not obvious can be repeated application, if necessary, can also increase the dose to 25mg intravenous, can also be continuous infusion of intravenous pump, Uladil 100mg diluted to 50mL (intravenous drip maximum drug concentration of 4g / L), the recommended initial rate of 2mg / min The recommended initial rate is 2mg/min, and the rate is adjusted according to the need of lowering blood pressure. Uraldil has few adverse effects, but dizziness, nausea, and palpitations may occur with rapid intravenous infusion. Contraindications are aortic isthmus stenosis or arteriovenous shunts (except for hemodynamically ineffective dialysis shunts).
(2) Phentolamine: Phentolamine is an adrenergic receptor blocker that increases cardiac output by reducing peripheral resistance and decreasing cardiac afterload and pulmonary artery pressure. It is indicated for hypertensive crisis caused by pheochromocytoma and hypertension combined with heart failure. Usually start with small doses, 5-10mg intravenously each time, and repeat after 20-30min as needed, or give 0.5-1mg/min intravenous drip. Due to the peripheral vasodilation caused by anti-catecholamines, individual patients may experience headache, tachycardia, facial flushing, and even severe postural hypotension. It is contraindicated in patients with severe atherosclerosis, hepatic and renal insufficiency, gastroduodenal ulcer, and acute coronary syndrome.
5.2.4 Beta-blockers
Esmolol: It is a very short-acting selective β1 receptor blocker, and the selectivity gradually disappears at high doses. It can block β1 receptors to reduce cardiac output, inhibit renin release, and block central β receptors to reduce peripheral sympathetic nerve activity, thus exerting antihypertensive effects. It is suitable for all types of hypertensive emergencies except for acute heart failure, especially for blood pressure control during the perioperative period including surgical anesthesia.
The drug is mainly metabolized by esterases in the cytoplasm of erythrocytes and does not affect liver or kidney function. The immediate control dose of this drug is 1mg/kg administered intravenously over 30s, followed by 0.15mg/(kg-min) intravenous drip, with a maximum maintenance dose of 0.3mg/(kg-min). Bronchial asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second or third degree atrioventricular block, refractory cardiac insufficiency, cardiogenic shock and hypersensitivity to this product are prohibited.
6.Drug selection for different target organ lesions in hypertensive emergencies
7.Summary
There is still some controversy about the optimal management of hypertensive emergencies. First, before deciding on the patient management process, patient history should be considered, then the target value of blood pressure lowering should be determined, the speed of blood pressure lowering, and the appropriate antihypertensive drug should be selected according to patient comorbidities. For patients with acute hypertension, intravenous drug antihypertensive therapy is recommended, and oral drugs are used to slowly lower blood pressure in patients with subacute hypertension.
Overly aggressive blood pressure lowering may lead to inadequate blood supply to tissues and organs, while inadequate blood pressure lowering can lead to increased morbidity and mortality in patients due to persistent hypertension, which can cause organ function damage. Moreover, strongly fluctuating blood pressure can also cause damage to target organs and blood vessels. Therefore, it is also necessary to adjust the speed of drugs and effectively control blood pressure in the appropriate range according to the condition during the antihypertensive process. In clinical practice, the principles of individualization, starting with small doses and adjusting according to the target value of blood pressure lowering are followed to lower blood pressure rapidly and smoothly in a planned and step-by-step manner to better protect target organs and improve the prognosis of hypertensive critical illness.