Drugs to lower blood pressure (Table 12.15)
While deepening the anesthetic or adding opioids will correct hypertension from light anesthesia, many patients require further blood pressure control. We have many agents at our disposal, with varying mechanisms of action.
The older propranolol (Inderal®) was not selective and blocked both β1 and β2 receptors, thus getting some patients into trouble with bronchoconstriction. Nevertheless, when it became available it represented a major advance in the treatment of hypertension, myocardial ischemia, and ventricular arrhythmias.
Frequently used today are labetalol (Normodyne®; Trandate®) and esmolol (Brevibloc®), two beta-blockers selective for the β1 receptors with just a weak β2 blocking component. Labetalol has the added advantage of some α1 blocking effect, perhaps 1/7th as strong as its β1 effect, thus enhancing its antihypertensive action with a little peripheral vasodilatation. It has a long duration of action, lasting several hours. Typical intravenous doses start with 10 mg for the average adult. If necessary, these doses can be repeated in 2- or 3-minute intervals, three or four times.
Esmolol has two characteristics that make it useful in special circumstances: it exerts a prominent effect on heart rate and has a rapid onset and relatively short duration with a half-life of under 10 minutes. The typical bolus dose is 0.25–1.0 mg/kg while infusions of 50 mcg/kg/min may be used for a more sustained effect.
Beta blockers are widely used in anesthesia where the common tachycardia sec-ondary to surgical stimulation or with tracheal intubation can lead to a mismatch of myocardial oxygen supply (reduced time for coronary perfusion) and demand (tachycardia, particularly when matched with hypertension). In addition to its intra-operative use, several studies have demonstrated that prophylactic use of beta blockers, e.g., metoprolol, throughout the perioperative period reduces car-diac morbidity and mortality. This is particularly true for patients with coronary artery disease.
When an elevated blood pressure cannot, or should not, be lowered by beta blockade or by deepening anesthesia, and particularly when we wish to have minute-to-minute control of blood pressure, we need agents with rapid onset of action and short duration. To meet this need routinely, the body liberates nitric oxide from the vascular endothelium, which has a fleeting effect of relaxing vas-cular smooth muscle. Two frequently used drugs, nitroglycerin and nitroprusside, appear to work by forming nitric oxide, so intimately involved in the tone of blood vessels. Both drugs take effect within a minute and will dissipate within 5 minutes. A direct vasodilating hypotensive agent, hydralazine (Apresoline®), finds less use because of its slow onset (up to 10 minutes) and its long duration (up to 4 hours) of action. However, its long, safe track record makes it a favorite in the obstetric suite.
Widely used in cardiology in the treatment of angina, nitroglycerin dilates vascular smooth muscle, with a preponderance of effect on venous over arterial vessels. For angina, a typical dose might be a 0.4 mg tablet under the tongue. As a hypotensive agent to lessen intraoperative bleeding, we infuse nitroglycerin intravenously at a rate of 0.5 to 1 mcg/kg/min. It is important to permit such low doses time to show their effect before adjusting the dose upward (potentially up to 10 mcg/kg/min in tolerant patients) in order to avoid hypotension and a stormy up and down of blood pressure by impatiently adjusting the infusion rate.
Nitroglycerin has the reputation of relieving coronary spasm and subendo-cardial ischemia, and thus it finds use when ST-segment depression or flipped T waves signal myocardial distress. Reduced ventricular pressure and cardiac out-put, without a marked rise in heart rate, help to re-establish a favorable balance of myocardial oxygen demand and supply.
In doses similar to those for nitroglycerin, i.e., starting an infusion of 0.5 to 2 mcg/kg/min and up to 10 mcg/kg/min, if needed, nitroprusside appears to have a more pronounced effect on arterial vessels and the pulmonary vascular bed than nitroglycerin. In the brain, sodium nitroprusside dilates vessels and interferes with autoregulation, which can present problems to patients at risk of increased intracranial pressure. The biotransformation of nitroprusside can lead to methemoglobinemia and, in extreme cases, to the liberation of cyanide. To minimize the chance of this toxicity, we monitor the total dose and keep it well below 0.5 mg/kg/h.
Clonidine occupies an interesting position in the classical scheme of drugs. On the one hand, it looks a little like a catecholamine, without chemically belonging to this category; on the other hand, it stimulates alpha adrenergic receptors – but α2 instead of α1. Thus, it inhibits adrenergic stimulation and decreases sympa-thetic influence on the heart and peripheral vascular bed, resulting in bradycardia and hypotension. As such, the drug finds use in the treatment of hypertension. Anesthesiologists must be aware that the sudden discontinuation of clonidine medication can trigger rebound hypertension.
Clonidine also produces mild sedation and analgesia. It has been used both orally and mixed with local anesthetics to enhance and prolong analgesia (see Local anesthetic additives).
This interesting gas hides behind a mouthful term, namely the “endothelium-derived relaxing (vasodilatory) factor” or EDRF for short. Its precursors reside in neurons, vascular endothelium, and macrophages. Once synthesized intracellu-larly, the very short-lived nitric oxide (NO) triggers a cascade of steps leading to the relaxation of vascular smooth muscle. As soon as a potential therapeutic role of NO had been appreciated – without a full understanding of its different physiologic roles – industry made it available as a gas that now finds application in treatment of patients with acute respiratory distress syndrome (ARDS). Short-term inhala-tion of tiny concentrations of NO (about 20 ppm) appears to be beneficial in this difficult clinical syndrome.