Critical Care Medicine

From Critical Care Medicine and Trauma, sponsored by the University of California, San Francisco, School of Medicine

Educational Objectives

The goal of this program is to improve the management of acute heart failure and shock. After hearing and assimilat­ing this program, the clinician will be better able to:

1.   Describe the management of volume overload using vasodilators, including nitroprusside, nitroglycerin, and nesiritide.

2.   Recognize the signs and symptoms of cardiorenal syndrome in a patient with acute decompensated heart fail­ure.

3.   Compare the agents used in the management of shock, including phenylephrine, norepinephrine, epinephrine, dopamine, dobutamine, and vasopressin.

4.   Identify shock of different etiologies, including cardiogenic, hypovolemic, obstructive, septic (inflammatory), and medication-induced.

5.   Discuss the findings of comparative studies of agents used in the management of shock.

Faculty Disclosure

In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and mem­bers of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this

educational activity promotes quality in health care and not a proprietary business or commercial interest.

For this program, the faculty and planning committee reported nothing to disclose.

Acknowledgements

This program was recorded at Critical Care Medicine and Trauma, held May 28-30, 2009 in San Fran­cisco, CA, and sponsored by the University of California, San Francisco, School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of this pro­gram.

Medical Management of Acute Heart Failure: The Internists’ Perspective

Mary O. Gray, MD, Associate Professor of Medicine, University of California, San Francisco, School of Medi­cine

Volume overload: total volume overload often seen in coronary care unit (patients often neglect preexisting cardiac conditions); pulmonary volume overload of more concern in critical care; usually due to left ventricular diastolic dysfunction; patients in ambulatory care setting often “on the brink,” but managing to function; examples  —  patients with left ventricular hypertrophy due to chronic hypertension; coronary disease; diabetes; elderly pa­tients; older women with these conditions at especially high risk; acute precipitants include pain, anemia, tachy­cardia, and acute cardiac ischemia or infarction

Diuretics: guidelines issued by American Heart Association (AHA) and American College of Cardiology (ACC) support use of loop diuretics first (eg, furosemide [Lasix] or bumetamide [Bumex]); dose should induce diure­sis, optimize volume status, and relieve congestion without drastic swings in intravascular volume

Diuretic Optimization Strategies Evaluation (DOSE) study: testing 2 hypotheses; first hypothesis  —  low-intensi­fication furosemide (equivalent to standard oral dose) better at relieving symptoms and safer for renal function than high-intensification furosemide; second hypothesis  —  continuous furosemide infusion safer and more ef­fective than twice-daily bolus

Vasodilators: when used with diuretic, relieve congestion more quickly in patients with acute decompensated heart failure (ADHF); may also help relieve chest pain (angina); two-thirds to three-quarters of patients with ADHF normo- or hypertensive, so vasodilators effective in that setting also; combination of vasodilators and diuretics improves absorption of oral cardiac medication

Major vasodilators: nitroprusside  —  many patients with ADHF do not feel well enough to take oral medications; as congestion and edema increase, absorption of oral medication often becomes more difficult; intravenous va­sodilators circumvent absorption problem and easy to titrate; “a very effective way to start a vasodilator”; con­cerns include theoretical possibility of coronary steal (leading to relative loss of circulation to myocardium and possible ischemia) and possibility of thiocyanate (cyanide) toxicity; actual toxicity relatively rare because drug used only in low doses and for short periods; nitroglycerin  —  rapidly reduces pulmonary venous congestion; usually used in acute setting (first or second hour); classically recommended as agent of choice for patients with severe hypertension, ischemia, or mitral valve regurgitation; main drawback rapid development of toler­ance, with subsequent reduction of efficacy; also some evidence that patients with heart failure (HF) more re­sistant to vasodilatory effects of nitroglycerin than those receiving it for other indications; nesiritide  —  human B-type natriuretic peptide (Natrecor); data supporting its use stronger than those for nitroprusside or nitroglyc­erin; produces fastest relief of congestive symptoms; biggest drawback (other than cost) possible nephrotoxic­ity; renal issues and effects on mortality now under investigation

Cardiorenal syndrome: patients hospitalized with ADHF often develop renal dysfunction; sometimes classified as mild, moderate, or severe (depending on glomerular filtration rate [GFR]); defined by others as worsening renal function during treatment (increase in creatinine >25% over baseline); equally common in diastolic and systolic heart failure; left ventricular filling pressure (pulmonary capillary wedge pressure) only parameter sig­nificantly associated with worsening renal function; no significant association with cardiac output or blood pressure, so focusing exclusively on increasing cardiac output not likely to resolve cardiorenal syndrome; per­sistent congestion  —  may occur despite dosing with furosemide at 240 mg/day, or in combination with other diuretics; determine whether patient candidate for dialysis and treatment for advanced HF; consider pulmonary artery catheter-guided therapy; imaging studies of kidneys often not as helpful as expected

Tachyarrhthmias: rate control first priority with atrial fibrillation in any patient with ADHF; rhythm control second priority; equally important, but rhythm harder to control, so controlling rate probably confers similar degree of benefit; hard to control sinus rhythm in acute care setting, so speaker recommends improving patient’s volume status and reducing ventricular response

Key questions: whether patient has pacemaker or implantable cardioverter defibrillator; status of left ventricular systolic function (preserved or reduced); duration of atrial fibrillation (if longstanding, goal of rate control rather than conversion to sinus rhythm may be appropriate); medications patient currently taking; whether patient has other medical conditions

Cardiogenic shock: state of end organ hypoperfusion caused primarily by cardiac failure; acute myocardial infarc­tion with left ventricular failure most common etiology; consists of persistent hypotension, severe reduction in car­diac index, and adequate or elevated left filling pressure; critical to assess patient for suitability of advanced treatment; consider presence of other medical conditions (eg, aortic dissection); also consider possible mechanical complications (eg, papillary muscle rupture); management  —  dopamine often used in coronary care unit at San Francisco General Hospital; dopamine and milrinone used more often in critical care; no evidence favoring either one, but both considered last-resort treatment; diuretics and vasodilators associated with better survival; inotropes possibly cardiotoxic, and often associated with less favorable outcomes; most useful for rescuing patient nearing end of life, when considering aortic balloon pump placement or implantation of ventricular assist device

Vasopressors and Inotropes

Judith Hellman, MD, Associate Professor in Residence, Anesthesia and Perioperative Care, University of Cal­ifornia, San Francisco, School of Medicine

Shock states: cardiogenic, hypovolemic, obstructive, and distributive; medication often exacerbates effects of hypo­tension and shock in intensive care unit (ICU); obstructive  —impairment of normal blood flow through obstruction of outflow or inflow; distributive  —  shock associated with systemic inflammatory processes (septic shock)

Drugs used to treat shock in ICU: primarily adrenergic agents; discussed below in decreasing order of a and in­creasing order of b activity

Phenylephrine: primarily a-agonist; potent vasoconstrictor with reflex effects on heart (bradycardia and decreased cardiac output); classically used to treat hypotension caused by vasodilation secondary to epidural or spinal anes­thesia or analgesia; also used to manage autonomic instability or effects of vasodilator; may help “temporize” pa­tient while awaiting access for other agents or volume resuscitation; occasionally used to counteract tachycardia due to norepinephrine or dopamine

Norepinephrine: most frequently used; binds to a- and b-receptors (minimal b₂ effect); considered potent vasocon­strictor rather than inotrope, but also increases cardiac rate and contractility; used to manage combined vasodila­tion and cardiac dysfunction; often employed in treatment of hypotension due to sepsis or other systemic inflammatory processes

Epinephrine: more b effect and vasoconstriction potency than norepinephrine; drawbacks include increased tachy­cardia and myocardial work load; generally used in management of severe myocardial dysfunction that contrib­utes to shock; classically used in treatment of acute cardiac arrest (can be administered intratracheally if intravenous access unavailable); also treats anaphylaxis

Dopamine: binds to adrenergic and dopaminergic receptors; effects go from b to a as dose increases; doses high enough to achieve vasoconstriction can induce tachycardia (some clinicians prefer norepinephrine); however, often used to treat shock from systemic inflammatory processes; classically used to increase urine output (low-dose, dopaminergic effect), although few data support practice; Surviving Sepsis Campaign recommends against it

Dobutamine: primarily b-agonist, with more b₁ than b₂ activity; strong inotrope; increases cardiac output; increases heart rate; in patient with severe cardiomyopathy, effect sometimes unpredictable (b₂ effect may lower blood pressure, but b₁ enhances contractility); used to treat cardiogenic shock, or refractory shock due to sepsis or other systemic inflammatory processes; not first choice, due to risk for tachyarrhythmias and hypotension

Vasopressin: helps regulate blood pressure; causes vasoconstriction and vasodilation of vascular beds; levels de­cline in sepsis; some data suggested that administration improved blood pressure and urine output and possibly decreased mortality; led to wide use in patients with sepsis and other systemic inflammatory processes; current uses  —  septic shock; pericardiopulmonary bypass; cardiopulmonary resuscitation or advanced cardiopulmonary life support (instead of epinephrine); longstanding or persistent hypotension due to use of angiotensin-converting enzyme inhibitor; animal evidence suggests even low doses may inhibit gastrointestinal blood flow (consider­ation if patient has compromised bowel function)

Vasoactive drug management of shock states

Cardiogenic shock: main problem poor contractility, with increased vascular tone or vascular resistance; start with dobutamine; if shock complicated by tissue hypo-perfusion and vasodilation, choose norepinephrine or epineph­rine; phosphodiesterase inhibitors (eg, milrinone) may also be used

Hypovolemic shock: fluid resuscitation major goal; multiple comorbidities may contribute to hypotension; pressors can maintain blood pressure

Obstructive forms of shock: inflow problems  —  eg, cardiac tamponade, pneumothorax; administer fluids, resolve problem (no important role for pressors); outflow problems; eg, pulmonary embolism, aortic coarctation, aortic stenosis, or pulmonary hypertension; judicious fluid administration plus inotropes or inotropes plus vasoconstric­tors; systemic inflammation leading to vasodilation indicates need for mixed inotrope and vasoconstrictor

Medication-induced shock: may result from vasodilation or cardiac dysfunction, depending on drug; classic mani­festation hypotension with neuraxial blockade; treat with phenylephrine; treat vasodilator-induced shock with phenylephrine also (use norepinephrine if systemic inflammation contributing); for cardiac depressant-induced shock, use pure inotrope or drug that increases vasoconstriction as well as cardiac contractility

Shock associated with inflammation: includes systemic inflammatory response syndrome (SIRS); decreased vascu­lar tone leads to increased vascular capacitance (capillary leak sometimes contributes to hypotension); de­creased cardiac contractility, even with elevated cardiac output and stroke volume

Vasopressin in Septic Shock Trial (VASST): patients initially treated with norepinephrine, then received either vasopressin or more norepinephrine; 778 patients randomized; no reduction in 28-day or 90-day mortality as­sociated with vasopressin; no significant differences in serious adverse events; authors’ conclusion  —  no over­all benefit with vasopressin; advantages of vasopressin (despite study findings)  —  useful as additional therapy for acidemic patients with inadequate response to norepinephrine; speaker recommends considering vasopres­sin for patients with septic shock already receiving mid-range dose of epinephrine; patients who develop tachydysrhythmias on norepinephrine or epinephrine, with extreme acidemia (low pH does not inactivate vaso­pressin), or already receiving high doses of pressors; also consider for patients on advanced cardiopulmonary life support or pericardiopulmonary bypass

Norepinephrine plus dobutamine vs epinephrine alone: 330 patients in septic shock randomized; no reduction in 28-day mortality associated with combination treatment; no difference in any secondary end points; no signifi­cant differences in serious adverse events; authors’ conclusion  —  no significant differences between treat­ments

Sepsis Occurrence in Acutely ill Patients (SOAP) study: observational study of 1,058 patients with shock (462 with septic shock) in 198 ICUs; 80% of patients treated with norepinephrine; found more dopamine and nor­epinephrine use in nonsurvivors; concluded dopamine represents independent risk factor for mortality

Portuguese community-acquired sepsis study: multicenter observational study comparing dopamine and norepi­nephrine; 458 patients with septic shock in 17 ICUs; norepinephrine associated with worse outcome and con­sidered independent risk factor for ICU mortality; results conflict with last study; speaker recommends more clinical trials to resolve

Recommendations from Surviving Sepsis campaign: norepinephrine and dopamine first-choice vasopressors for managing septic shock; epinephrine, phenylephrine, and vasopressin should not be initial vasopressors; vasopres­sin may be added subsequently to other pressors; epinephrine first choice as alternative if patient poorly respon­sive to norepinephrine or dopamine; use of low-dose dopamine to improve renal perfusion not well-supported by data; dobutamine recommended to treat myocardial dysfunction

Suggested Reading

Annane D et al: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 370:1034, 2007; Dellinger RP et al: Surviving Sepsis Campaign: international guidelines for management of se­vere sepsis and septic shock: 2008. Crit Care Med 36:296, 2008; DiMarco John P: Atrial fibrillation and acute decompen­sated heart failure. Circulation: Heart Failure 2:72, 2009; Fares WH: Management of acute decompensated heart failure in an evidence-based era: what is the evidence behind the current standard of care? Heart Lung 37:173, 2008; Howlett JG: Current treatment options for early management in acute decompensated heart failure. Can J Cardiol 24:9B, 2008; Liang KV et al: Acute decompensated heart faiure and the cardiorenal syndrome. Crit Care Med 36:S75, 2008; Noviasky JA: Controversy and conflict in the treatment of acute decompensated heart failure: limited role for nesiritide. Pharmacotherapy 27:626, 2007; Póvoa PR et al: Influence of vasopressor agent in septic shock mortality. Results from the Portugese Community-Acquired Sepsis (SACiUCI) study. Crit Care Med 37:410, 2009; Russell JA et al: Vasopressin versus norepinephrine infusion in pa­tients with septic shock. N Engl J Med 358:877, 2008; Sakr Y et al: Does dopamine administration in shock influence out­comes? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) study. Crit Care Med 34:589, 2006; Townsend SR et al: Reducing mortality in severe sepsis: the Surviving Sepsis Campaign. Clin Chest Med 29:721 2008.