Labetalol

The statistics on high blood pressure and stroke are sobering: every year, about 600 000 persons in the United States have a stroke (83% ischemic, 17% hemorrhagic). (1) Roughly half of those persons have hypertension,' and hypertension develops after stroke in many patients who were previously normotensive. (2) In the landmark 1996 National Institute of Neurological Disorders and Stroke (NINDS) trial of recombinant tissue plasminogen activator (rtPA) in patients with stroke, 19% of the subjects were hypertensive at the time of their acute ischemic stroke; within 24 hours, that rate had tripled. (3) For these reasons, critical care nurses need expertise in managing hypertension in patients who have had an acute ischemic stroke.

Comprehensive stroke protocols include administration of alteplase (rtPA) for acute ischemic stroke and provide guidelines for management of hypertension; intravenous labetalol (Normodyne, Trandate) is often recommended. (4-8) Although intravenous labetalol is often used in critical care units and medical units, its administration as an intravenous infusion may not be common, and many nurses may not be knowledgeable about blood pressure issues related to patients who have had an acute ischemic stroke.

In this article, I focus on the nursing considerations for management of hypertension, including administration of labetalol, in patients with acute ischemic stroke treated with rtPA. In addition, I describe the relationships among cerebral blood flow, blood pressure, and stroke: concepts that direct guidelines for care. This overview is appropriate for staff nurses who work in emergency, intensive care, and medical units. Nurse educators and managers involved in the development of stroke protocols and educational programs also will find the information useful.

11:30 PM

Meet Ruth

Your night shift is just getting started when the telephone rings. The emergency department has admitted 68-year-old Ruth Casey. Diagnosis? Acute ischemic stroke. Treatment? Thrombolytic therapy with alteplase.

You listen to the report, assign a bed, and check the equipment in the room. If you are like many nurses, you also pull out the policy and procedure book because your community hospital has not been using this treatment for very long; you want to review the details of the new pathway.

12:15 AM

Ruth arrives awake and alert with slight residual hemiparesis on the right side, a right-sided facial droop, and dysarthria. The rtPA was administered in the emergency department, and now an isotonic sodium chloride solution is being infused intravenously at a rate of 50 mL/h. Neurological findings and vital signs are unchanged from those in the report, except for the blood pressure, which has increased to 220/100 mm Hg. Heart and respiratory rates are stable. Oxygen saturation is fine at 98%. Ruth answers, "No," when you ask if she is in pain.

1:30 AM

You set the blood pressure auto-cuff, pet-form another neurological assessment, and notify the physician. Ten minutes pass quickly; the blood pressure is unchanged. The physician determines that the pressure must be treated and prescribes labetalol, 10 mg administered intravenously over 2 minutes, followed by an infusion if necessary.

1:45 AM

You have the labetalol vials in front of you. For years you have given labetalol to your patients with myocardial infarction; you are familiar with its cardioprotective effects. But have you ever administered it as an infusion? Are you aware of the mixing guidelines? The precautions? The concerns about patients' safety? Can you explain why treatment of hypertension in this patient must be approached delicately?

Normal Physiology of Cerebral Blood Flow

Complex autoregulatory mechanisms seek to maintain cerebral blood flow at a constant rate of about 750 mL/min. (9) The 2 main regulatory factors are cerebral perfusion pressure and cerebral vascular resistance. Cerebral perfusion pressure, the blood pressure gradient across the brain, is in turn influenced by mean arterial pressure and intracranial pressure. Like vascular resistance elsewhere in the body, cerebral vascular resistance is determined by the diameter of the vessels. In response to elevated blood pressure (from any cause), cerebral vessels constrict, restricting cerebral blood flow to a homeostatic rate. Thus, "myogenic autoregulation" (9) protects the brain from increasing intracranial pressure by limiting cerebral intravascular volume (see Figure).

Cerebral myogenic autoregulation can usually accommodate a wide range of fluctuations in blood pressure, from a mean arterial pressure as low as 60 mm Hg (2,9,10,12) to a high of 120 mm Hg (10) or even 150 mm Hg. (2,9,12) In chronic hypertension, however, both limits are shifted upward. This shift in limits must be considered when treating stroke patients who have preexisting chronic hypertension. Although autoregulation adjusts to broad variations in blood pressure, it will fail when brain tissue is injured, when intracranial pressure becomes extremely high (>40 mm Hg (9)), or when mean arterial pressure is outside the patient's usual range. Once autoregulation fails, cerebral blood flow becomes passively regulated by the systemic mean arterial pressure.

Finally, metabolic factors that act independently of the perfusion pressure affect cerebral blood flow. Increased metabolic rate (fever), hypercapnia (in both local brain tissue and the blood), acidosis, hypoglycemia (<70 mg/100 mL), (2) and hypoxia all stimulate cerebral vasodilation and a subsequent increase in cerebral blood flow. Conversely, hypocapnia and alkalosis cause vasoconstriction.

Mechanisms for Hypertension in Acute Ischemic Stroke

After a stroke, hypertension can develop in previously normotensive patients for a variety of reasons. Sudden and severe hypertension, particularly after administration of alteplase, is alarming because it may indicate--or cause--intracerebral hemorrhage. In addition to hypertension, signs and symptoms of intracerebral hemorrhage include neurological decline, new headache, nausea, and/or vomiting. Any indication that a patient may have intracerebral hemorrhage demands immediate discontinuation of the rtPA, reassessment of neurological function, and emergent computed tomography. (4,7,8,13,14)

Conversely, hypertension may be a vital compensatory mechanism, promoting perfusion to threatened brain tissue. Cerebral ischemia, the consequence of occlusion of the cerebral artery by an embolus or a thrombus, damages the cellular sodium-potassium pump. This damage permits, among other things, an influx of sodium and water; the cells swell, cerebral edema ensues, and intracranial pressure becomes elevated. Without a corresponding increase in blood pressure, cerebral perfusion pressure would be impaired (see Figure).

Furthermore, higher than normal blood pressure may be of particular importance in the protection of the ischemic penumbra, a zone of injured, but still viable, brain tissue that surrounds the central core of infarction. Although the ischemic penumbra is temporarily perfused by collateral circulation, as increasing intracranial pressure impairs brain perfusion, the collateral vessels dilate. (12) Sustaining cerebral perfusion pressure through the dilated vessels requires a greater blood pressure.

In addition to stroke, hypertension may be associated with other acute conditions such as aortic dissection, myocardial infarction, unstable angina, acute renal failure, pulmonary edema with respiratory failure, eclampsia, pheochromocytoma, and microangiopathic hemolytic anemia. Finally, emotional stress, bladder distention, pain, and hypoxia can cause elevations in blood pressure after a stroke." Searching for the cause of hypertension is vital to prescribing the most appropriate therapy.

Treatment of Hypertension in Patients With Ischemic Stroke Treated With Alteplase

In the NINDS trials, treatment of hypertension correlated with less favorable outcomes than did untreated hypertension. This unexpected finding led the researchers to advocate "careful attention to" but "gentle management" of blood pressure, (3) a position that is echoed throughout the literature. (10,11,15-17) Although reluctant to define optimal blood pressure for patients after acute ischemic stroke, experts in the management of stroke do agree about when high blood pressure should be treated.

The American Heart Association defines high blood pressure as either a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure less than 90 mm Hg. (18) As a result of the NINDS trials, however, parameters for stroke treated with rtPA are considerably higher. During and/or after administration of rtPA, 2 successive measurements, taken 5 to 10 minutes apart, should meet 1 or both of the following criteria before antihypertensive agents are given (3,4,6-8) systolic blood pressure greater than 180 mm Hg or diastolic blood pressure greater than 105 mm Hg. (Note: rtPA is contraindicated in stroke patients with sustained systolic blood pressures >185 mm Hg or diastolic blood pressure >110 mm Hg who are unresponsive to either nitroglycerin paste or a maximum of two 10- to 20-mg doses of intravenous labetalol. (4-8)

High blood pressure in patients who have had an ischemic stroke is managed with restraint; the risk of intracerebral hemorrhage must be weighed against the need to preserve perfusion to the ischemic penumbra. When treatment is indicated, the drug used should have a rapid onset, a predictable effect, a low risk for causing precipitous decreases in blood pressure, a minimal effect on cerebral blood flow, and a relatively short half-life; it should also be easy to titrate. Because it meets most of these standards, labetalol is recommended for these patients. (3-10,14,15,19,20)

Actions and Effects of Labetalol

Labetalol is a complex medication. It acts on [alpha]- and [beta]-receptor sites in distinct locations in the heart, lungs, and vasculature. Specifically, labetalol is a selective, postsynaptic [[alpha].sub.1]-adrenergic blocking agent and a nonselective, [beta]-adrenergic blocking agent (Table 1). Because of its unique combination of actions, labetalol decreases systemic blood pressure and vascular resistance without markedly affecting cardiac output, renal hemodynamics, or cerebral blood flow.

Labetalol is metabolized in the liver and excreted in the urine. After intravenous injection, its effects occur within 5 minutes, peak within 15 minutes, and persist at least 2 to 4 hours (effect lasting 24 hours has been reported). The half-life is 5.5 hours. (21-23)

Contraindications and Precautions

Contraindications (Table 2) and precautions (Table 3) for administration of labetalol are related to the effects of the drug on the sympathetic nervous system. Although it may not produce the same degree of sympathetic blockade as pure [alpha]- or [beta]-adrenergic blockers, restrictions for each of these categories are generally applied to labetalol. (21-26) The manufacturers also urge caution in administering labetalol to patients with ischemic heart disease (myocardial infarction and exacerbation of angina have been documented), vasospastic angina or pheochromocy toma (paradoxical hypertensive crisis has been reported for both), and severe hepatic dysfunction (labetalol metabolism may be impaired; the drug can also further injure hepatocytes). Pregnant women (pregnancy category C: may be harmful to the fetus) and nursing women (small amounts excreted in breast milk) should receive this medication only when the benefit outweighs the risks and when alternatives are not available. Finally, safety and efficacy of labetalol in children have not been established for intravenous administration. (22,23)

Drug Interactions

Standard nursing practice calls for obtaining a thorough and accurate medication history before a new drug is administered. Today, this history must include information on use of over-the-counter medicines and herbal remedies, some of which have long-acting effects. Because patients may not consider over-the-counter drugs and herbal remedies when reporting their medication lists, nurses must specifically ask about these preparations (Table 4).

Adverse Effects and Reactions

Most of the undesirable effects of labetalol appear to be dose related, are both mild and transient, and occur early in treatment. Because labetalol blocks the ability of the heart to pump faster in response to changes in body position, dramatic orthostatic hypotension can occur. Symptomatic postural hypotension is the most common adverse effect, (21-25) and patients may experience dizziness, light-headedness, and/or syncope.

Other serious adverse effects include increased atrioventricular block, bradycardia, worsening of heart failure, ventricular arrhythmia, dyspnea, wheezing, and bronchospasm. In addition, after intravenous administration, at least 5% of patients experience l or more of the following: scalp tingling, nausea, and transient elevated serum levels of urea nitrogen and creatinine (in patients with preexisting renal insufficiency). (22,23) Management of overdose is aimed at countering the effects of the sympathetic blockade (Table 5).

Guidelines for Administration of Labetalol in Patients With Acute Ischemic Stroke Treated With rtPA

Mixing Guidelines

Labetalol must be diluted for intravenous infusion and can be mixed in most common intravenous solutions such as isotonic sodium chloride solution and 5% dextrose in water. Both commercial preparations of labetalol are supplied in vials that contain 5 mg/mL. Three specific solutions, 1.25 mg/mL, 2.5 mg/mL, and 3.75 mg/mL, are stable for at least 24 hours. (21,30,31) In addition, more dilute preparations of l mg/mL or 2 mg/3 mL may be prepared. (21-23,25,26,30,31) Table 6 offers mixing guidelines for each of these 5 concentrations.

Drug Compatibilities and Incompatibilities

When mixed with 5% dextrose in water in a 1:1 solution, labetalol is compatible for 24 hours with the medications listed in Table 7. It is incompatible with alkaline solutions.

Recommended Dose and Administration

Labetalol is administered by repeated bolus doses given by slow intravenous injection or by continuous infusion until the desired blood pressure is achieved. The benefits of continuous infusion may include greater control of antihypertensive action as well as milder and fewer adverse effects (including hypotension). (32) Once the target blood pressure is reached, the infusion can be stopped, (21-25) although it is sometimes continued for 24 hours (A. M. Pancioli, MD, University of Cincinnati Medical Center, e-mail, August 21, 2001); in either instance, once the infusion is discontinued, an oral regimen is considered (21-25) (A. M. Pancioli, MD, e-mail, August 21, 2001). An infusion pump is necessary for safe administration. Refer to Table 6 for a titration chart and to Table 8 for a specific dosing regimen. Although the manufacturers recommend a maximum cumulative bolus dose of 300 mg, (22,23) a maximum of 150 mg is recommended for patients with ischemic stroke treated with rtPA. (3,4,6-8,14,20)

Promoting Patients' Safety

The goal of hypertension management in acute ischemic stroke is gradual and controlled reduction in blood pressure to a prescribed value. (17) Avoiding precipitous decreases in blood pressure reduces the likelihood of hypoperfusion injury to the brain, myocardium, kidneys, (10,22,23) and optic nerve. (22,23) Nursing interventions are outlined in Table 9.

And Ruth?

By 2 AM, you had administered a bolus dose of 10 mg of labetalol intravenously. Ruth's blood pressure changed but remained elevated. The physician ordered a labetalol infusion with a target systolic blood pressure of 185 mm Hg. To limit the intravenous fluid intake, you mixed a solution of 3.75 mg/mL and titrated the infusion accordingly. Ruth's systolic blood pressure gradually improved, and as it neared the target value, you discussed further treatment with the physician.

5:30 AM

Throughout the past few hours, you have continued to assess Ruth's vital and neurological signs. You have also monitored for post-thrombolytic complications. Finally, you have created a restful environment for her and have offered ongoing support and information to Ruth and her family. It has been a busy night!

Summary

As community hospitals adopt comprehensive stroke pathways, nurses in critical care areas must prepare for each possible complication. Although the thrombolytic component of a new stroke protocol may receive the most attention, the various details of the pathway--in this case, management of blood pressure--should not be overlooked. Critical care nurses who appreciate the considerations for treatment of hypertension and who can correctly and efficiently administer intravenous labetalol may save precious time and enhance outcomes for patients with stroke who have hypertension.

Acknowledgments

The author thanks Jeanne Bruno-Joyce, RPh, clinical pharmacy coordinator, from the intensive care unit at Wentworth Douglass Hospital, Dover, NH, for her assistance in preparing this manuscript.

References

(1.) American Heart Association. 2002 Heart and Stroke Statistical Update. Dallas, Tex: American Heart Association; 2002. Available at: http://www.americanheart.org. Accessed February 1, 2002.

(2.) Dolan JT. clinical Management Through the Nursing Process. Philadelphia, Pa: FA Davis co; 1991.

(3.) Brott T, Lu M, Kothari R, et al. Hypertension and its treatment in the NINDS rt-PA Stroke Trial. Stroke. 1998;29:1504-1509.

(4.) Adams HP Jr, Brott TG, Furlan AJ, et al. Guidelines for thrombolytic therapy for acute stroke: a supplement to the guidelines for the management of patients with acute ischemic stroke. A statement for healthcare professionals from a Special Writing Group of the Stroke council, American Heart Association. Circulation. 1996;94:1167-1174.

(5.) Broderick JP. Guidelines for medical care and treatment of blood pressure in patients with acute stroke. National Institute of Neurological Disorders and Stroke. Reviewed July 1, 2001. Available at: http://www.ninds.nih.gov/health_and_medical/stroke_proceedings/brodri ck.htm. Accessed February 1, 2002.

(6.) Jauch E. The "golden hour" of acute ischemic stroke: post-treatment guidelines and recommendations. Internet Stroke center. Last revised March 26, 2001. Available at: http://www.strokecenter.org/education/jauch. Accessed February 1, 2002.

(7.) Lappin R. Thrombolysis for stroke: a user's guide. Emerg Med. September 1999;31:54-64.

(8.) Brott TG, clack WM, Fagan SC, et al. Stroke: the first hours. Guidelines for acute treatment. National Stroke Association. 2000. Available at http://www.stroke.org/pages/pro_firsthours.cfm. Accessed February 1, 2002.

(9.) Hickey JV. The Clinical Practice of Neurological and Neurosurgical Nursing. 4th ed. Philadelphia, Pa: JB Lippincott; 1997.

(10.) Varon J, Marik PE. The diagnosis and management of hypertensive crisis. Chest. 2000;118:214-227.

(11.) Thelan L, Lough M, Urden L, Stacy K. Critical Care Nursing: Diagnosis and Management. 3rd ed. St Louis, Mo: CV Mosby; 1998:830.

(l2.) Powers WJ. Acute hypertension after stroke: the scientific basis for treatment decisions. Neurology. 1993;43:461-467.

(13.) Vance DL. Treating acute ischemic stroke with intravenous alteplase. Crit Care Nurse. August 2001;21:25-32.

(14.) Hock NH. Brain attack. Nurs Clin North Am. 1999;34:689-723.

(15.) Adams HP Jr, Brott TG, Crowell RM, et al. Guidelines for the management of patients with acute ischemic stroke: a statement for healthcare professionals from a Special Writing Group of the Stroke Council, American Heart Association. Dallas, Tex: American Heart Association; 1994. Available at: http://www.americanheart.org/presenter.jhtml?identifier=1227. Accessed February 1, 2002.

(16.) Foley JJ. Pharmacologic management of hypertensive crisis in the emergency department. J Emerg Nurs. 1994;20:134-135.

(17.) Bahouth MN, LaMonte MP. Update on stroke prevention and initial acute stroke management. Lippincotts Prim Care Pract. 2000;4:545-562.

(18.) American Heart Association. About high blood pressure. Dallas, Tex: American Heart Association; 2002. Available at http://www.americanheart.org/presenter.jhtml?identifier=468. Accessed February 1, 2002.

(19.) Torbey MT, Bhardwaj A. Blood pressure management in acute ischemic stroke: selecting agents, avoiding pitfalls. J Crit Illin. 2000;15:590.

(20.) Pancioli A, Kothari R. Thrombolytic therapy for acute isehemic stroke. Air Med J. April-June 1999;18:56-61.

(21.) McEvoy GK, ed. American Hospital Formulary Service Drug Information. Bethesda, Md: American Society of Health-System Pharmacists Inc; 2001.

(22.) Normodyne [package insert]. Kenilworth, NJ: Schering Corp; September 1999.

(23.) Trandate [package insert]. Research Triangle Park, NC: Glaxo Wellcome Inc; December 1999.

(24.) Reent S, ed. Clinical Pharmacology [book on CD-ROM]. Tampa, Fla: Gold Standard Multimedia; 2001.

(25.) Cada DJ, ed. Drug Pacts and Comparisons. 2001 ed. St Louis, Mo: Facts and Comparisons; 2001:480-482.

(26.) Gahart BL, Nazareno AR. Intravenous Medications: A Handbook for Nurses and Allied Health Professionals. St Louis, Mo: CV Mosby; 2001:554-557.

(27.) Jenkins AP. Herbal energizers: speed by any other name. J Phys Educ Recreation Dance. Feb 1997. Available at Central Washington University Web site at: http://www.cwu.edu/%7Ejenkinsa/speed.html. Accessed January 29, 2002.

(28.) Kolecki P. Sympathomimetic toxicity. June 11, 2001. Available at: http://www.emedicine.com. Accessed January 29, 2002.

(29.) The natural pharmacist. Available at http://www.tnp.com. Accessed January 29, 2002.

(30.) Catania PK. King Guide to Parenteral Admixtures. Naps, Calif: King Guide Publications Inc; 2001.

(31.) Trissel LA. Handbook of Injectable Drugs. 11th ed. Bethesda, Md: American Society of Health-System Pharmacists Inc; 2001:775-778.

(32.) Wright JT Jr, Wilson DJ, Goodman RP, Minisi AJ. Labetalol by continuous infusion in severe hypertension. J Clin Hypertens. 1986:2:39-43.

(33.) Perry HM Jr, Davis BR, Price TR, et al. Effect of treating isolated systolic hypertension on the risk of developing various types and subtypes of stroke: the Systolic Hypertension in the Elderly Program (SHEP).JAMA. 2000;284:465-471.

(34.) Gueyffier F, Boissel J-P, Boutitie F, et al. Effect of antihypertensive treatment in patients having already suffered from stroke. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators. Stroke. 1997;28:2557-2562.

Cindy Harrington is a staff nurse in the intensive care unit at Wentworth Douglass Hospital, Dover, NH.

COPYRIGHT 2003 American Association of Critical-Care Nurses
COPYRIGHT 2003 Gale Group