Learning Objectives

At the conclusion of this educational activity, participants should be able to:

• Recognize appropriate indications for intravenous fluid bolus therapy in the setting of syncope.
• Identify contraindications for beta-blockers in the setting of acute decompensated heart failure.
• Describe effective treatments for hypertensive emergencies.
• Discuss appropriate Emergency Department disposition for patients during hypertensive emergencies, and barriers to admitting high-risk patients to intensive or stepdown care.

The Case

The patient was a 55-year-old woman with a history of panic attacks, class III obesity, and previously untreated hypertension who presented to the emergency department (ED) for an episode of syncope while sitting at church. On arrival, the patient reported a prodrome of flushing, diaphoresis, and lightheadedness. She lost consciousness for an unknown length of time and awoke with a headache but no confusion. Initial vital signs included a severely elevated blood pressure (BP) of 218/177 mm Hg, borderline heart rate of 102 beats per minute, and low oxygen saturation of 90% on room air. Electrocardiography (ECG) showed sinus tachycardia without ischemic changes. She was given an intravenous (IV) bolus of one liter of normal saline and ibuprofen for her headache.

Laboratory testing was notable for creatinine 1.83 mg/dl with unknown baseline, brain natriuretic peptide (BNP) markedly elevated at 3723 pg/mL, and troponin-I elevated at 1.20 ng/mL. Computed tomography (CT) of the head without contrast was negative for acute intracranial processes, but the chest x-ray showed pulmonary edema. After these results, the working diagnosis changed to acute heart failure exacerbation and the patient was given furosemide 40 mg IV. To treat her hypertension, she was given two doses of labetalol 10 mg IV and admitted to the general ward after her systolic BP dropped below 160 mm Hg. The next morning, while she remained as a boarder in the ED awaiting transfer to the ward, the patient’s systolic BP was again over 200 mm Hg, and she was given isosorbide mononitrate 60 mg by mouth. Her blood pressure failed to improve, and she developed oliguria. Cardiology was consulted and recommended to transfer the patient to the cardiac intensive care unit (ICU) for continuous nitroglycerin infusion.

After transfer to the ICU, a transthoracic echocardiogram showed global hypokinesis with an ejection fraction (EF) of about 20% (i.e., less than half the normal value). Despite nitroglycerin infusion, the patient developed worsening hypoxic respiratory failure and somnolence requiring intubation. Immediately after intubation, the patient suffered cardiac arrest; the initial rhythm was pulseless electrical activity (PEA). After two cycles of cardiopulmonary resuscitation (CPR), spontaneous circulation returned. Magnetic resonance imaging (MRI) of the head showed a left cerebellar hypodensity concerning for ischemic stroke, intraventricular hemorrhages in the right hemisphere, and signs of increased intracranial pressure. An external ventricular drain was emergently placed, but she failed to make meaningful neurologic improvement. The patient’s spouse and children agreed to transition the goal of care to comfort, after which she was extubated and died.

The Commentary

By Jaenic Lee, MD, Josh Fernelius, MD, and William Frick, MD

This patient with previously untreated hypertension presented after a syncopal episode in church, preceded by a prodrome of flushing, diaphoresis, and lightheadedness. She was quickly recognized as having a hypertensive emergency with end-organ effects on her cardiopulmonary system and kidneys. However, it was not immediately recognized that she was in acute heart failure with left ventricular dysfunction and hypervolemia, leading to mismanagement of her hypertensive emergency, irreversible progression of cardiac injury, and a fatal hemorrhagic stroke.

Syncope is a common ED presentation with a broad differential diagnosis that includes multiple potential cardiovascular and non-cardiovascular causes. Considering there are many etiologies of syncope in which the patient may be volume-depleted, an intravenous (IV) fluid bolus is a reasonable part of initial management in many patients. Furthermore, it is common practice to administer fluids to hospitalized patients with evidence for improved outcomes in patients with non-cardiac conditions.¹ However, the patient in this case presented with signs of volume overload including hypoxemia, pulmonary edema on chest x-ray, and elevated troponin and BNP. In this case, there was a probable contraindication to IV fluids, which have been associated with worse outcomes when administered inappropriately in heart failure.¹ After completing their initial evaluation, the treating clinicians changed course, administering IV loop diuretics in accord with usual practice in acute decompensated heart failure.² It is not clear from the case report what factors drove the decision to start with a crystalloid bolus, but up to 10-20% of patients admitted to US hospitals with heart failure receive crystalloid followed by diuretics, perhaps reflecting the fact that signs of volume overload can be subtle and not apparent when patients first present to the ED.¹

The presence of pulmonary edema with hypoxemia and acute kidney injury, in the setting of hypertension, was indicative of hypertensive emergency at presentation, not hypertensive urgency. Once severe hypertension is linked to end organ damage, that is an indication for rapid blood pressure control using a titratable drip.³ For emergent management in the setting of pulmonary edema and suspected heart failure, combined preload and afterload control with a nitroglycerin drip and intensive monitoring may permit optimal titration of dosage.^3,4 Trials have not demonstrated significant adverse effects of IV nitroglycerin when used during heart failure exacerbations.³ Clevidipine and nicardipine are dihydropyridine calcium channel blockers that can also be given by continuous infusion to safely treat hypertensive emergencies.^5,6 Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have also been shown to be beneficial in reducing afterload in this setting, but ACE/ARB therapy was not immediately indicated for this patient given the uncertain condition of her kidneys.⁴

As a combined alpha/beta adrenergic blocker, labetalol is seen as an attractive choice in the ED because of its rapid onset of action when given IV.⁴ However, there are reasons to be cautious with labetalol, as its alpha blocking properties address the problem of increased afterload, but its beta blocking properties reduce inotropy and chronotropy.⁷ In addition, labetalol has not been shown to reduce morbidity and mortality in heart failure, unlike carvedilol and metoprolol.^8,9,10 Beta blockers have an important role in the management of heart failure with reduced ejection fraction (HFrEF), but this therapy should be started after the patient’s cardiac afterload has been reduced (i.e., after initiation of a renin-angiotensin-aldosterone system or angiotensin receptor/neprilysin inhibitor) and volume overload has been corrected.^2,11,12 In this case, labetalol may have been chosen as a way to emergently lower the blood pressure while sparing the patient continuous infusion, which would have required admission to an ICU.

ICU level care may be a limited resource in busy hospitals, and ED staff are expected to help manage this resource effectively by limiting ICU admissions to the most critically ill patients. In this patient’s case, after two doses of IV labetalol controlled the blood pressure, she appeared to be safe for admission to the general medical ward. By the time the effects of labetalol wore off, she had already been seen by the admitting team and orders had been written to cover her care overnight. Between her admission evaluation in the ED and her re-evaluation by the day team on the medical ward, there was clinically apparent deterioration requiring a higher level of care. Therefore, it is reasonable to ask whether disposition to a higher level of care, with more frequent monitoring and greater nursing attention, may have prevented the poor outcomes in this case. For a patient with only one “ICU level need” (i.e., a titratable infusion), a stepdown unit may have been appropriate; however, many hospitals do not have such units or limit them to patients coming out of the ICU. This predicament apparently led to repeated administration of “as needed” anti-hypertensives to keep the patient’s condition appropriate for admission to a medical ward, which led to patient harm.

The patient’s hospital course was then complicated by a hemorrhagic stroke, but there is no way to know whether more effective treatment of her hypertensive emergency would have prevented this complication. The patient likely had severe hypertension for several years without treatment and severe heart failure with an ejection fraction of about 20% before her syncopal episode and arrival in the ED. HFrEF is known to be associated with poor outcomes such as stroke.¹³ Furthermore, the etiology of her heart failure was not known, but it seems likely attributable, at least in part, to decompensated hypertensive cardiomyopathy.

With hindsight, it is reasonable to conclude that the initial fluid bolus and repeated administration of beta blockers may have contributed to the patient’s poor outcome. It is unclear why the patient initially received a fluid bolus, and whether clinicians assessed for signs of heart failure with hypervolemia, such as orthopnea (dyspnea when supine), bendopnea (dyspnea when bending forward at the waist for 30 seconds, while sitting in a chair), jugular venous distension, and hepatojugular reflex (sustained increase of jugular venous pressure by >3 cm with 10 seconds of continuous abdominal pressure).¹⁴ Higher rates of late critical care admission, late intubation, late renal replacement therapy, and in-hospital death have been observed in heart failure patients who received IV fluids versus those who did not.¹

The patient was given IV furosemide after crystalloids, but she may have benefited from doses higher than 40 mg due to her worsening kidney function, likely from cardiorenal syndrome. While labetalol initially helped control the patient’s blood pressure, she experienced persistent hypertension with an especially elevated diastolic pressure. Maintenance of cardiac output in patients with acute heart failure depends in part upon sympathetic drive.⁷ The administration of a beta blocker likely worsened perfusion in the setting of acute heart failure.¹⁵ The patient may have responded better to a parenteral nitrate such as nitroglycerin (given that nitroprusside is relatively contraindicated in the setting of acute kidney injury) or a calcium channel blocker such as nicardipine or clevidpine.

Approaches to Improving Patient Safety

Fluid and volume management

The patient may have benefited from immediate diuresis after initial examination in the ED to offset her volume overload rather than the IV fluid bolus that exacerbated it. In this patient’s case, it is unclear what indication led to fluid administration, but ED physicians in a high-stress environment managing several patients concurrently must make rapid decisions based on limited information. Syncope has different risk stratifications depending on cardiac versus noncardiac etiologies, and ED physicians may have more cumulative experience with vasovagal and orthostatic syncope than with cardiac causes of syncope, such as heart failure and cardiomyopathy with decreased cardiac output.¹⁶ In this situation, “availability bias” may lead to reflexive use of IV fluids as initial therapy for all patients with syncope. A more thoughtful, evidence-based approach to fluid and volume management¹ might emphasize assessing fluid balance and documenting goals before administering crystalloid boluses. Proper use of checklists, treatment algorithms, or clinical decision support tools might prevent similar mistakes in the future.

Disposition

This patient had several signs of end-organ damage and high-diastolic pressure with narrow pulse-pressure; admission to a general medical ward before resolution of these issues was not conducive to patient safety. Admission to a cardiac stepdown or critical care unit would have allowed more active blood pressure management and closer observation. It is necessary to query the system of care to understand better why the clinicians on both ends of the admission decision felt comfortable with such a risky choice. Were all ICU beds full at the time of admission, with administrative or clinical barriers to transferring a low-risk patient out of the ICU to open a bed? Were stepdown beds eliminated or unavailable due to nursing shortages or other factors? Was there implicit bias related to the patient’s obesity, lack of prior treatment for hypertension, religion, or unreported social factors such as race or education? Was the overnight nursing supervisor or the charge nurse on the receiving unit empowered to raise questions about the appropriateness of admission to a general medical ward? Hospitals should consider implementing policies and procedures that direct patients with high-risk admitting diagnoses, such as hypertensive emergency with pulmonary edema, to intensive care, perhaps allowing for carefully justified exceptions.

Conclusion 

Implementing these approaches to improving patient safety may not have changed the outcome for the patient in this case, but clinicians must be cautious in administering the same set of typical interventions to all patients with common presenting complaints, such as syncope. Avoiding universal administration of fluid boluses, caution in treating hypertensive emergencies, choosing appropriate antihypertensives for patients with end-organ injury, and emphasizing patient safety-centered disposition from the ED may help to prevent future morbidity and mortality.

Take-Home Points

• Multiple factors can contribute to treatment errors in the acute care setting.
• Initiation of beta blockers should be avoided in acute decompensated heart failure, at least until hypervolemia and cardiogenic shock have been resolved.
• Intravenous fluids should not be given without a reasonable indication.
• Hypertensive emergencies warrant ICU admission, even if the blood pressure responds acutely to intravenous medications such as labetalol.

Jaenic Lee, MD
Resident Physician 
Department of Internal Medicine
West Virginia University
jaenic.lee@hsc.wvu.edu

Joshua Fernelius, MD
Resident Physician
Department of Internal Medicine
Saint Louis University
Joshua.Fernelius@slucare.ssmhealth.com

William Frick, MD
Cardiology Fellow
Department of Cardiovascular Medicine
Saint Louis University
William.Frick@slucare.ssmhealth.com

Acknowledgements: The editorial team thanks Dr. William R. Lewis with the Department of Cardiology at UC Davis Health for his peer review of this commentary.

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