Board Review Session II Wednesday, August 17, 2011 Questions and Answers and Rationales
15. A patient is receiving volume assist-control ventilation and his ventilator graphics are depicted as “Baseline” in the Figure. The top tracing in the Figure is flow, the second tracing is volume, the third tracing is airway pressure, and the bottom tracing is esophageal pressure. An aspiration event producing parenchymal lung injury occurs. Which set of tracings is most consistent with this?
a. Panel A b. Panel B c. Panel C d. Panel D
16. Curve A is the intraoperative capnograph of a 67-year-old man who underwent left carotid endarterectomy 6 hours ago. He has diabetes and hypercholesterolemia. Findings of preoperative pulmonary assessment, including full pulmonary function tests, are normal. Evaluation is requested for sudden hypotension and chest pain. There is no change in pulse oximetry readings or lung auscultation. Which of the following capnographs most suggests acute myocardial infarction as a cause
for this patient's symptoms?
a. Capnograph A b. Capnograph B c. Capnograph C d. Capnograph D
17. A man with an exacerbation of chronic obstructive pulmonary disease has required mechanical ventilatory support for the past 5 days. This morning, his gas exchange has improved, his airway obstruction seems less, and he is easily triggering every breath on the ventilator. A spontaneous breathing trial (SBT) is initiated and, although he does well initially, he becomes tachypneic and tachycardic, and his SpO2 drops after 1 hour. The best way to manage this patient's ventilatory support is to: a. Abandon further SBTs, place him on substantial pressure support (PS) ventilation and wean the pressure level as tolerated b. Abandon further SBTs, start a combination of synchronized intermittent mandatory ventilation (SIMV) and PS, then sequentially wean the SIMV and PS as tolerated. c. Repeat the SBTs every 6 hours and provide stable PS ventilation in between. d. Repeat the SBTs every 24 hours and provide stable PS ventilation in between. e. Repeat the SBTs every 24 hours and suppress all spontaneous efforts in between.
18. A 34-year-old woman is receiving mechanical ventilation for bilateral lung contusions. She is receiving volume assist-control ventilation (tidal volume, 6 mL/kg ideal body weight; plateau pressure, 23 cm H2O; positive end-expiratory pressure, 5 cm H2O; FIO2, 0.40; SpO2, 93%) and has been heavily sedated for over 72 hours. As a consequence, she never triggers the ventilator and relies on the ventilator set rate. Under these circumstances, she is particularly at risk for:
a. Intracranial hypertension b. Oxygen toxicity c. Ventilator-induced diaphragmatic dysfunction d. Pneumothorax 19. A patient is being ventilated with the mode depicted in the Figure below (top tracings depict flow; middle tracings, volume; bottom tracings, pressure). The left panel is a stable baseline. Flash pulmonary edema develops and the graphics change to the right panel. Which of the following ventilation modes behaves like this? a. Pressure-regulated volume control ventilation b. Pressure support ventilation
c. Volume assist-control ventilation d. Airway pressure release ventilation
20. In cardiogenic shock following myocardial infarction, which of the following therapies will produce all of the following hemodynamic and myocardial effects: an increase in mean arterial pressure, a decrease in systemic vascular resistance (afterload), an increase in myocardial oxygen supply (coronary blood flow), and a decrease in myocardial oxygen demand? a. Norepinephrine b. Milrinone c. Dobutamine d. Intraaortic balloon counterpulsation 21. A 48-year-old man enters the ICU with a 2-hour history of severe (10/10), substernal, nonradiating chest pain. He notes some pain reduction with leaning forward. He has mild
nausea but not shortness of breath or diaphoresis. His father had a myocardial infarction at the age of 49. He takes no medications and has no other past medical history. His pulse rate is 82/min, BP is 160/90 mm Hg, temperature is 38.2°C (100.8°F), and RR is 18/min. His physical examination findings are normal. His ECG is shown in the Figure below. A cardiac catheterization laboratory is not available. Which of the following therapeutic agents should be administered to this patient?
a. Tenecteplase (TNK-tPA) b. Ibuprofen c. Abciximab d. Heparin
22. A 72-year-old woman enters the ICU with an acute inferior myocardial infarction and bradycardia at 56/min. She has a past history of atrial fibrillation and has received longterm warfarin therapy. She is treated with tenecteplase (TNK-tPA), heparin, aspirin, and captopril. Beta-blockers are held due to her bradycardia, and a temporary transvenous pacemaker is fluoroscopically positioned in the right ventricular apex with good sensing and pacing thresholds. The patient’s chest pain resolves about 30 minutes after tenecteplase administration. The patient’s ECG on the second hospital day is shown in the Figure below. In addition to an evolving inferoposterior myocardial infarction, the ECG shows which of the following?
a. Dual-chamber pacing b. Failure to capture only c. Failure to sense only d. Failure to sense and capture e. Rate-adaptive pacing
23. A patient with recent acute inferior myocardial infarction awaiting coronary artery bypass grafting develops recurrent chest pain and becomes unresponsive and pulseless during ECG. His ECG is shown in the Figure below. The patient has an IV line in place and receives direct electrical defibrillations, but he remains in the rhythm shown in the ECG. Cardiopulmonary resuscitation is continued with chest compressions and endotracheal intubation and ventilation. Which of the following is the most appropriate next management step?
24. A 45-year-old woman with recently diagnosed small cell lung cancer is admitted 12 hours after her first dose of chemotherapy with altered mental status and oliguria. Her BP is 95/60 mm Hg, HR is 88/min, and temperature is 37.3°C (99.1°F). Physical examination is remarkable for confusion and tetany. Her urinalysis shows needle-shaped crystals. The patient’s condition is associated with: a. Hypouricemia b. Hypercalcemia c. Low lactate dehydrogenase level d. High creatine kinase level
25. A 68-year-old woman with a history of depression and hyperlipidemia presents with onset of confusion and lethargy during the past 24 hours. Medications include sertraline and simvastatin. On examination, she is difficult to arouse and disoriented to time and
place. BP is 130/78 mm Hg, HR is 88/min, and she is afebrile. Her jugular venous pressure is 6 cm at 45°. Lungs are clear. She has no edema. She is noncooperative with neurologic examination, though no obvious focal findings are evident. Laboratory findings in serum include the following: sodium, 114 mEq/L; potassium, 3.8 mEq/L; blood urea nitrogen, 15 mg/dL; creatinine, 0.9 mg/dL; and glucose, 98 mg/dL. Urine sodium level is 48 mEq/L, with osmolality of 450 mOsm/kg H2O. Which of the following is the most appropriate first step in the management of her hyponatremia? a.Fluid restriction and observation with the goal of raising serum sodium level to 124 mEq/L in 24 hours b. IV 0.9% saline with the goal of raising her serum sodium level to 124 mEq/L in 24 hours c. IV 0.9% saline and furosemide with the goal of raising her serum sodium level to 130 mEq/L in 24 hours d. IV 3% saline with the goal of rapidly raising her serum sodium level to 118 mEq/L in 4 hours
26. An intensivist is called to a resuscitation of an elderly patient with a small bowel obstruction. The patient has vomitus coming out of her mouth and is hemodynamically unstable, with a systolic BP of 75 mm Hg. She is oxygenating on a face mask but is poorly responsive. Etomidate and 1.0 mg/kg of rocuronium are given and cricoid pressure is being held. Endotracheal intubation is attempted twice but the view is very poor. The patient is becoming more hypotensive and hypoxemic. Which of the following would be most useful in the next attempt at establishing an airway? a. Using another laryngoscopy blade b. Using a laryngeal mask airway c. Using a cricothyroidotomy kit d. Doing a blind nasal intubation e. Getting a smaller endotracheal tube 27. A 51-year-old woman with exertional angina is admitted to the ICU after having a cardiac arrest during an exercise test. Her prior medical history includes coronary artery disease treated with coronary artery bypass grafting 8 months ago, hypertension, hyperlipidemia, and diabetes. She currently takes extended-release metoprolol, 50 mg/day; ramipril, 2.5 mg/day; simvastatin, 80 mg day; aspirin, 81 mg/day; metformin, 500 mg 3 times daily; and repaglinide, 2 mg 3 times daily. During the recovery phase of the exercise test, the patient collapsed and the ECG shown in the Figure was obtained. The ECG shows which of the following rhythms?
Comment [A1]: ECG missing
a. Atrial fibrillation with a bundle-branch block b. Wolff-Parkinson-White syndrome c. Ventricular fibrillation d. Ventricular tachycardia 28. A 52-year-old woman with dilated cardiomyopathy and heart failure enters the ICU because of increasing dyspnea and weight gain during the past week. An arterial and pulmonary artery catheter are placed. Baseline and postmedication hemodynamics are shown below. Following Drug Baseline Administration Parameter Blood pressure (mm Hg) 100/60 90/60 Right atrial pressure (mean, mm Hg) 15 8 Right ventricular pressure (mm Hg) 40/15 25/10 Pulmonary artery pressure (mm Hg) 40/30 25/15 Pulmonary artery occlusion 28 15 Pressure (mean, mm Hg) Cardiac output (L/min) 2.0 2.6 Urine output (mL/h) 10 140 The hemodynamic change depicted in the table is most consistent with the administration of which of the following medications? a. Nesiritide b. Dopamine c. Norepinephrine d. Angiotensin
29. A 74-year-old man enters the ICU with fever and hypotension. He has a history of kidney stones with multiple previous bouts of urinary tract infection. Urine and blood cultures are obtained, and vancomycin and ceftazidime are started. Presently, his BP is 70/40 mm Hg. Two liters of normal saline do not raise the blood pressure, and a thermodilution pulmonary artery catheter is inserted, revealing low right-sided heart filling pressures, a pulmonary artery occlusion pressure of 16 mm Hg, and a cardiac output of 13.7 L/min. An infusion of norepinephrine increases the blood pressure to 100/70 mm Hg. An infusion of vasopressin, 0.01–0.03 U/min, is also started. Which of the following statements most accurately reflects the evidence on the effectiveness of vasopressin, 0.01–0.03 U/min, as administered to this patient? a. Patients on doses of norepinephrine >15 µg/min demonstrate an improved survival if so treated. b. When added to norepinephrine, it is associated with an increase in episodes of acute ischemic heart disease. c. Given with norepinephrine, it produces a mortality rate at 28 days that is comparable to therapy with norepinephrine alone. d. It has little or no effect on the ability to decrease norepinephrine dose using a target mean arterial pressure of 65 to 75 mm Hg.
15. Correct Answer: B. Panel B Rationale: Because the mode is volume assist-control, the set volume is constant regardless of respiratory system mechanics in all four panels. In contrast, the airway and the esophageal pressure profiles are markedly different. In all four choices, the peak airway pressures are elevated, but only in B and C are the plateau pressures (pressures at end-inspiration with no flow) elevated. Thus panels B and C are the only two patterns reflecting a worsening respiratory system compliance, as would occur with a parenchymal lung injury such as our patient experienced. The esophageal pressure allows us to separate the lung and the chest wall compliance contributions to the plateau pressure in panels B and C. If the elevation in plateau pressure is due to a chest wall effect such as obesity, ascites, anasarca, or chest bandages, the esophageal pressure will be elevated, as in panel C. However, if abnormal lung mechanics are producing the acutely elevated plateau pressure, the esophageal pressure will not change. Thus, panel B best represents an acute parenchymal lung injury, as in our patient. Panels A and D reflect flow-related pressure elevations, as might occur with increased airway resistance (panel A) or an increased flow setting (panel D). 16. Correct Answer: B. Capnograph B Rationale: Arterial end-tidal PaCO2 gradient is a function of dead-space ventilation, and in the absence of significant pulmonary disease, end-tidal partial pressure of carbon dioxide (PetCO2) is several millimeters of mercury less than the pressure of arterial carbon dioxide (PaCO2). The major factors that alter this gradient are lung disease and change in cardiac output. An acute change in the gradient without a significant change in capnographic configuration indicates a change in cardiac output. In our case, curve A represents the baseline capnograph; curve B shows a widened P(arterial to end-tidal [aet])CO2 gradient while the morphology of the capnograph is similar to the baseline curve, suggesting an acute change in cardiac output as a cause for the patient's instability. Curves C and D, although suggestive of a widened P(a-et)CO2 gradient show different morphologies than curve A. This difference in morphology suggests, in addition, changes in pulmonary mechanics as an explanation for the observed changes. 17. Correct Answer: D. Repeat the SBTs every 24 hours and provide stable PS ventilation in between. Rationale: The evidence strongly supports daily spontaneous breathing trials (SBTs) as the best way to assess ventilator discontinuation potential in patients with stable or recovering respiratory failure. Specifically, in two large trials evaluating ventilator weaning and withdrawal techniques in such patients, no strategy was faster than simply evaluating the patient daily with an SBT and maintaining a stable level of substantial ventilatory support in between. Indeed, strategies focused only on gradual support reductions without daily SBTs can actually slow the withdrawal process if support
reductions are not timely. Moreover, because gradual support reductions require a high level of monitoring and frequent ventilator adjustments, personnel time and resource consumption can be increased. Options A and B are thus wrong. While more frequent SBTs (option C) may be useful in patients with rapidly reversible respiratory failure (eg, drug overdose, asthma, transient need for neuromuscular blockers for procedures), lung injury recovery patterns are such that SBTs more frequent than every 24 hours are not helpful. Option C is thus wrong in this patient with chronic obstructive pulmonary disease. The difference between options D and E is the approach to the stable ventilatory support between the daily SBTs. Animal studies have shown that muscle atrophy and delayed fatigue recovery occurs when the inspiratory muscles are made totally inactive (option E). Moreover, sedation needs may increase if the goal is to totally suppress all inspiratory activity. Thus, the preferred ventilatory mode should probably be a comfortable interactive mode such as pressure support (option D) with the inspiratory pressure level titrated to comfort. 18. Correct Answer: C. Ventilator-induced diaphragmatic dysfunction Rationale: Ventilator-induced diaphragmatic dysfunction (VIDD) describes ventilatory muscle abnormalities induced by mechanical ventilation strategies that suppress or eliminate spontaneous ventilatory muscle activity. These strategies generally involve high-level assist-control support modes designed to have patients perform little or no work to receive ventilatory support. Ventilatory muscles thus receive virtually no neural stimulation and have virtually no muscle loading. Under circumstances of no neural input or muscle loading, a number of changes have been described in the ventilatory muscles that resemble peripheral skeletal muscle atrophy. Complicating this is the fact that VIDD co-occurs with other causes of muscle injury (eg, critical illness myopathy, corticosteroids, neuromuscular blockers) and it may be difficult to clinically discern its relative importance. Nevertheless, it seems prudent to avoid prolonged conventional mechanical ventilation and allow spontaneous inspiratory efforts as soon as feasible with appropriate levels of mechanical ventilatory support. While options A, B, and D may all be complications of mechanical ventilation, they are not the best choices in the clinical setting described here. The patient's intrathoracic pressures are not high enough to significantly raise intracranial pressures or produce pneumothorax, her FIO2 is in a range that minimizes oxygen toxicity, and her lack of inspiratory efforts makes dyssynchrony a nonissue. 19. Correct Answer: A. Pressure-regulated volume control ventilation Rationale: The left panel of the figure depicts a pressure-targeted mode with the typical square wave of pressure and the exponentially decelerating inspiratory flow pattern. With abruptly changing respiratory system mechanics such as flash pulmonary edema, traditional pressure-targeted modes (ie, pressure assist-control and pressure support) will
maintain the set airway pressure but produce smaller tidal volumes. That appears to be the case in the first breath of the lower panel. However, over the next several breaths, the ventilator automatically increases the inspiratory pressure to restore the previous tidal volume. This is characteristic of the pressure-regulated volume control mode (option A). The pressure-regulated volume control mode is designed to provide the synchrony and gas mixing effects of pressure targeting while “guaranteeing” a set tidal volume. A similar feedback algorithm can be applied to pressure support in the volume support mode. 20. Correct Answer: D. Intra-aortic balloon counterpulsation Rationale: The hemodynamic and myocardial effects of an increase in mean arterial pressure and a decrease in systemic vascular resistance coupled with an increase in myocardial oxygen supply (coronary blood flow) and a decrease in myocardial oxygen demand are typical of effective treatment with intra-aortic balloon counterpulsation (IABC). IABC provides a balloon inflation-induced augmentation of blood pressure and flow during ventricular diastole. With effective IABC, the mean arterial pressure increases because of the added balloon-assisted pressure wave during diastole. Overall, stroke volume and cardiac output are increased, leading to a reduction in systemic vascular resistance and afterload. The IABC also increases diastolic blood flow into the coronary vessels, probably because of direct balloon inflation and an overall improvement in hemodynamics from restoration of blood pressure and cardiac output. This constellation of hemodynamic and myocardial effects is ideal for the management of cardiogenic shock because it optimizes the systemic and cardiac circulations in the face of major ventricular failure and shock. No pharmacologic agent is able to produce these hemodynamic and myocardial effects. Norepinephrine’s vasoconstrictor properties increase blood pressure and increase systemic vascular resistance; norepinephrine increases myocardial oxygen demand because of the increase in afterload, and myocardial oxygen supply usually increases as a result of improvement in systemic blood pressure. Therefore, option A is incorrect. Dobutamine and milrinone both decrease systemic vascular resistance by vasodilation and increase cardiac output because of their inotropic actions; however, blood pressure usually decreases, especially with milrinone, so options B and C are incorrect. Dobutamine causes an increase in both myocardial oxygen demand and supply because of its beta1-adrenergic inotropic stimulation. Myocardial oxygen consumption usually increases with dobutamine. Milrinone has a somewhat more potent vasodilator effect than dobutamine, so milrinone also increases myocardial oxygen supply and demand; however, the increase is more balanced, so that myocardial oxygen consumption is usually unchanged. 21. Correct Answer: B. Ibuprofen Rationale: The patient’s chest pain improves somewhat on leaning forward, a characteristic commonly seen in pericarditis. The ECG shows diffuse ST-segment elevation located in the inferior (II, III, aVF), lateral (I, II, aVL), and most anterior (V3-
V6) leads. In addition, prominent PR depression is seen in leads II and aVF. Lead aVR shows PR-segment elevation and ST-segment depression. These diffuse ECG changes are typical of acute pericarditis, which should be treated with a nonsteroidal antiinflammatory agent (NSAID) such as ibuprofen. Option B is correct. The typical features of ECG abnormalities in acute pericarditis are the diffuse ST elevation commonly in all leads except aVR and V1 (as in this case) and PR-segment depression in several leads. The PR-segment elevation and ST depression in aVR are also typical of pericarditis. Treatment with an NSAID such as ibuprofen is usually effective. In resistant cases, indomethacin, colchicine, and rarely prednisone, are necessary to relieve symptoms. Since this patient has pericarditis, none of the other agents aimed at the coagulation system are indicated. Tenecteplase is a thrombolytic agent that would be indicated in treatment of an ST-segment elevation myocardial infarction (MI), with ST elevation in the leads corresponding to the occluded coronary artery. (Option A is incorrect.) Abciximab is a platelet IIb/IIIa receptor antagonist that would be indicated in acute STsegment elevation MI being treated with primary angioplasty. (Option C is incorrect.) Heparin is an antithrombin agent that should be used with tenecteplase, reteplase, or alteplase for reperfusion therapy during an ST-segment elevation MI. (Option D is incorrect.) In patients with more equivocal ECG findings, an echocardiogram may provide useful information to differentiate pericarditis from an ST-elevation MI. A patient with MI should have obvious wall motion abnormalities, and a patient with pericarditis may have some pericardial effusion. Elevation of troponin level may be seen in a minority of patients with pericarditis, presumably reflecting some asymptomatic myocarditis occurring with pericarditis. The troponin elevations are usually small and do not approach the magnitude seen with MI. 22. Correct Answer: D. Failure to sense and capture Rationale: The ECG shows atrial fibrillation with a moderate ventricular response and an evolving inferior myocardial infarction (Qs and ST elevation in leads II, III, and aVF) and posterior involvement (prominent R waves in V2 and V3 with ST depression in V2). The pacemaker artifacts (arrows) march through the entire tracing at a rate of 60/min, demonstrating that the pacemaker fails to sense the native rhythm. Pacemaker artifact numbers 1, 5, and 7 occur far enough outside the refractory period of the ventricle that they should produce capture if the pacemaker was capturing the ventricle. In this patient, the ventricular pacemaker wire had dislodged into the pulmonary artery outflow tract and was no longer sensing or capturing. Dual-chamber pacing refers to pacing both the atrium and ventricle with separate pacing wires. An atrial pacing wire was not placed in this patient, and atrial pacing would not be successful in atrial fibrillation. Rate-adaptive pacing refers to permanent pacemakers that
have special programming features that increase heart rate in response to hemodynamic or respiratory parameters. This form of permanent pacing was not used in this patient. 23. Correct Answer: B. Epinephrine Rationale: The patient developed ventricular fibrillation (VF) during the performance of an ECG for chest pain, probably ischemic in origin. Although the VF has a sinusoidal pattern suggestive of torsade de pointes, the patient has become unresponsive and pulseless, so this must be managed as a VF-induced sudden death. According to the American Heart Association’s recommendations, IV epinephrine injection, 1 mg repeated every 3-5 minutes, is the appropriate next step. An alternative to epinephrine (not a choice in this question) would be IV vasopressin, 40 units. The American Heart Association’s algorithm then recommends one minute of CPR and repeat electrical defibrillation with 360 J. Since epinephrine or vasopressin are the next steps in the accepted algorithm, the other answers are incorrect. Atropine may be useful in treating bradycardia, symptomatic heart block, asystole, or occasionally pulseless electrical activity with a slow rhythm. Calcium may be useful in managing hyperkalemia and hypocalcemia. An intra-aortic balloon pump would not be able to support the circulation of a patient with VF. An intra-aortic balloon pump needs a rhythm or an arterial waveform in order to assist the circulation. One needs to establish a rhythm and blood pressure in this patient before sending him for coronary artery bypass grafting. Insertion of a biventricular assist device (not a choice in this question) to fully take over cardiac function as a possible bridge to coronary artery bypass grafting has been described in a few reports of prolonged, unresponsive CPR. 24. Correct Answer: A. Hypouricemia Rationale: Tumor lysis syndrome (TLS) is observed after chemotherapy for rapidly growing tumors such as Burkitt lymphoma and leukemia. Recently, TLS has been observed in patients with solid tumors such as small cell lung cancer, metastatic lung cancer, and medulloblastoma. Hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia can appear as soon as 6 hours after chemotherapy and persist for 5 to 7 days after treatment. Serum calcium levels drop from ectopic calcium deposition; this becomes more likely as the calcium-phosphorus product increases. Needle-shaped urate crystals can form in the renal collecting ducts and result in oliguric and anuric renal failure. High creatine kinase level is a typical finding of rhabdomyolysis, not TLS. 25. Correct Answer: D. IV 3% saline with the goal of rapidly raising her serum sodium level to 118 mEq/L in 4 hours Rationale: This patient has the syndrome of inappropriate antidiuresis, probably because of sertraline. She presents with advanced neurologic complications of hyponatremia. Regardless of the duration of the hyponatremia, such symptoms demand prompt
treatment to avoid further complications from hyponatremic encephalopathy due to cerebral edema. Hypertonic saline is the treatment of choice, with the goal of increasing the serum sodium level by 2-4 mEq/L over a period of 2-4 hours. After this modest improvement, which is safe and advisable, then the patient should receive, in addition to fluid restriction, either more hypertonic saline or the combination of normal saline and furosemide while monitored every 2 hours. The goal is to correct her sodium level by no more than 12 mEq/L in the first 24 hours, and by no more than 18 mEq/L in 48 hours. Fluid restriction alone is not an acceptable treatment for symptomatic patients. Normal saline, with or without furosemide, has limited effect in euvolemic patients and should not be used in patients with severe symptoms. 26. Correct Answer: C. Using a cricothyroidotomy kit Rationale: The patient is becoming unstable and could arrest. Furthermore, she is paralyzed, so a blind nasal intubation cannot be done. Data has suggested that after two attempts, consideration of obtaining a surgical airway is appropriate in critically ill patients to prevent cardiac arrests. Furthermore, placement of a laryngeal mask airway will not protect against aspiration in a patient who clearly is at risk. Continuing to perform laryngoscopy is dangerous, unless a specific issue could be resolved with new equipment. Using a smaller endotracheal tube will not help if you cannot visualize the glottis. 27. Correct Answer: C. Ventricular fibrillation Rationale: The ECG shows coarse ventricular fibrillation. The patient was successfully defibrillated. Cardiac catheterization showed a total occlusion of the bypass graft to the obtuse marginal branch of the left circumflex coronary artery. Successful angioplasty and stenting of the native left circumflex coronary artery was performed. The ventricular fibrillation was probably the result of acute ischemia from the occluded bypass graft. 28. Correct Answer: A. Nesiritide Rationale: The hemodynamic effect was a mild decrease in blood pressure, moderate decrease in pulmonary and right heart pressures, and an increase in cardiac and urine output. Nesiritide is the only agent listed that could produce this hemodynamic profile. Nesiritide is a recombinant form of human B-type natriuretic peptide (BNP), which is a naturally occurring protein secreted by the heart as part of the response to acute heart failure. Nesiritide is a 32-amino-acid polypeptide that is synthesized using recombinant DNA technology. BNP is expressed by ventricular myocytes in response to pressurevolume overloading of the ventricles. It has vasodilating and natriuretic properties that counter the vasoconstricting and fluid retention effects of the renin-angiotensin system. Nesiritide binds to the natriuretic peptide receptor on the surface of vascular smooth muscle and endothelial cells and produces vasodilatation through a guanosine monophosphate pathway.
When given to patients with heart failure, nesiritide reduces pulmonary artery occlusion pressure, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance (SVR). Reduced SVR results in increased cardiac output. Thus, the agent produces a “balanced” vasodilator effect on the pulmonary and systemic vascular circuits. Nesiritide also produces a modest natriuretic and diuretic effect, and its hemodynamic effects will enhance the effect of loop diuretics. The drug elimination half-life is about 20 minutes, and all effect is gone 2 to 4 hours after discontinuation of infusion. It was approved by the FDA for treatment of acute heart failure in 2001. Of the other choices, dopamine, norepinephrine, and angiotensin would produce an increase in blood pressure and no change or an increase in pulmonary artery and pulmonary artery occlusion pressures. Hydralazine is a pure arteriolar vasodilator. It will produce a decrease in SVR and increase in cardiac output, but it will not produce a decrease in pulmonary artery or pulmonary artery occlusion pressures. 29. Correct Answer: C. Given with norepinephrine, it produces a mortality rate at 28 days that is comparable to therapy with norepinephrine alone. Rationale: A recently published, large, randomized, controlled trial, the Vasopressin in Septic Shock Trial (VASST) compared therapy using vasopressin plus norepinephrine to norepinephrine alone in 778 patients with septic shock. The study’s major finding was that, in septic shock treated with catecholamine vasopressors, low-dose vasopressin (0.01–0.03 U/min) did not reduce mortality compared to norepinephrine. Thus, option C is correct. VASST identified two prospectively defined subgroups of more severe septic shock, patients requiring at least 15 µg/min of norepinephrine, and less severe septic shock, those patients requiring <15 µg/min of norepinephrine. In the more severe septic shock group, there was no difference in the mortality rates between vasopressin and norepinephrine treatment groups (44% versus 42.5%, respectively, p = 0.76). Thus, option A is incorrect. However, and somewhat paradoxically, in the less severe septic shock group, vasopressin was associated with a lower mortality rate than norepinephrine (26.5% versus 35.7%, p = 0.05). The study’s authors consider this finding, though interesting, to be a subgroup analysis subject to all the statistical shortcomings of subgroups. This finding was judged to be hypothesis-generating, and future clinical trials should evaluate its validity. One of the major side effects of higher doses of vasopressin (usually in the 0.1–0.4 U/min range) was an increased incidence of acute ischemic heart disease, including myocardial infarction and death. Presumably, these adverse events resulted from vasopressin-induced coronary vasoconstriction. The low-dose regimen of 0.01–0.03 U/min was developed to avoid these side effects, and in fact, VASST had no increase in episodes of ischemic heart disease associated with vasopressin use. Thus, option B is incorrect. In fact, overall adverse events were the same in the vasopressin and norepinephrine groups.
Vasopressin is a powerful vasoconstrictor, and in VASST as well as multiple previous smaller vasopressin studies, vasopressin administration has resulted in a large decrease in norepinephrine dose when using a target mean BP of 65 to 75 mm Hg. Thus, option D is incorrect.