Hemodynamic Effects of Nesiritide and Dopamine in Cardiovascular Collapse Assessed Via Impedance Cardiography

We illustrate a case of a patient presenting after an intentional overdose of diphenhydramine who subsequently had progression to respiratory failure and hemodynamic collapse. To our knowledge, only one similar case has been reported in the literature in which an intra-aortic balloon pump was used to treat the patient. In contrast, our patient was treated with dopamine and nesiritide as well as serial hemodynamic measurements via impedance cardiography. After several days of therapy, the patient had a return to normal ejection fraction and hemodynamic stability. This treatment approach may provide a less invasive treatment option for similar patients while still rendering favorable patient outcomes. A 26-year-old black woman presented to the emergency department after taking 32 sleeping pills (25 mg of diphenhydramine per capsule) in a reported attempt to commit suicide. The patient had apparently taken the pills approximately 9 hours before arrival. Other than a history of bipolar disorder, her medical history was unremarkable. She had no history of drug or alcohol use and took no prescription medications. On arrival to the emergency room her physical examination revealed a somnolent 26-year-old black woman in mild distress. She was arousable to verbal stimuli. When aroused, she complained of nausea and chest pain. She described the pain as a pressure on the left side of her chest that was mild and did not radiate. She had no other associated signs or symptoms. Her vital signs revealed that she was hypertensive (163/120 mm Hg) and tachycardic (134 beats per minute). The initial electrocardiographic (ECG) results showed a sinus tachycardia with some ST segment elevation in the inferior leads; however, 2 subsequent ECG tests revealed resolution of the ST segment elevation. Findings from chest x-ray were normal. Chemistries showed that she was hypokalemic (2.8 mg/dL) and hyperglycemic (243 mg/dL). Complete blood cell count and urinalysis were unremarkable. Her creatine kinase-MB was normal but her first troponin-I was slightly elevated at 0.19 ng/mL. Brain natriuretic peptide (BNP) was elevated at 2870 pg/mL. The patient's serum drug screen was negative for routine drugs of abuse. The patient was admitted to the cardiac floor for chest pain to rule out acute coronary syndrome, hypertensive urgency, tachycardia, diphenhydramine overdose, hyperglycemia, and hypokalemia. She was placed on routine telemetry orders, moderate sliding-scale regular insulin, enoxaparin 40 mg SQ daily, intravenous replacement of potassium, and suicide precautions. Approximately 8 hours after admission, the patient became hypotensive and hypoxic. Serial cardiac enzymes demonstrated that she had sustained an acute myocardial infarction with elevated troponin-I levels of 5.42 ng/mL and 6.78 ng/mL at 8 and 16 hours after admission, respectively. Repeat BNP rose to 3170 pg/mL. She was then transferred to the intensive care unit (ICU) where intubation and central venous access were performed. An initial fluid bolus corrected her blood pressure (BP) (500 mL of normal saline improved pressure to 106/88 mm Hg); however, a repeat chest x-ray showed pulmonary edema. A spiral computed tomographic scan result of the chest was negative for pulmonary embolus. A limited 2-dimensional echocardiogram revealed a left ventricle that was dilated and hypokinetic and an echogenic area consistent with left ventricular apical thrombus. The enoxaparin dose was increased to 1 mg/kg SQ every 12 hours. The patient continued to be hypotensive and more tachycardic 24 hours after admission. She also developed a fever. All of these symptoms were consistent with an anticholinergic crisis due to diphenhydramine overdose. A dopamine drip was started to maintain her BP, and metoprolol was ordered as needed for a heart rate >140 beats per minute. On hospital day 2, impedance cardiography revealed that the patient had a low cardiac index, decreased stroke volume, and increased systemic vascular resistance (Table, Figure 1, Figure 2, Figure 3). On hospital day 3, it was decided to start the patient on nesiritide to improve her hemodynamics, with a bolus of 2 μg/kg, with the drip initiated at 0.01 μg/kg/min. Her BP was maintained with low-dose dopamine. Impedance cardiography results. Cardiac index. HD indicates hospital day and time. Impedance cardiography results. Systemic vascular resistance index. HD indicates hospital day and time. Impedance cardiography results. Stroke index. HD indicates hospital day and time. On hospital day 4, the patient became more hypotensive, leading to reduction of the nesiritide drip to 0.005 μg/kg/min. The drip rate was increased back to 0.01 μg/kg/min on hospital day 5 after improvement in the patient's BP. The nesiritide drip, along with dopamine, was maintained for the next 48 hours. Nesiritide was then discontinued on hospital day 7 and the patient continued on dopamine alone for another 48 hours. On hospital day 9, the patient started having recurrent symptoms of heart failure decompensation, leading to an additional 48 hours of nesiritide. By hospital day 11, the patient's hemodynamic status had improved sufficiently to allow discontinuation of both the nesiritide and dopamine. At that time, the patient was transferred from the ICU to the step-down unit for further treatment. During these drug titrations, hemodynamic status was frequently monitored by impedance cardiography. The Table shows the results of these tests along with the corresponding infusion rates of nesiritide and dopamine.Figure 1, Figure 2, and Figure 3 provide a graphic representation of the changes in the patient's cardiac index, systemic vascular resistance index, and stroke volume index, respectively. In addition to monitoring these hemodynamic markers, the patient's left ventricular function was monitored. A 2-dimensional echocardiogram obtained on hospital day 5 showed an ejection fraction of 25% with continued presence of the left apical thrombus seen on the first echocardiogram. A resting nuclear ventriculogram was obtained on hospital day 15 before patient discharge and showed a left ventricle with normal wall motion and an ejection fraction of 61%. Cardiovascular collapse following anticholinergic overdose has previously been reported in the literature.1 In this previous report, right-sided heart catheterization with thermodilution and pulmonary wedge pressure analysis gave very similar results: decreased cardiac output and increased systemic vascular resistance and a bedside 2-dimensional echocardiogram that revealed an estimated left ventricular ejection fraction of 20%. Multiple inotropic agents in addition to an intra-aortic balloon pump were implemented. These agents were able to be withdrawn on day 7 with complete resolution of symptoms. Drug therapy to help correct the hemodynamic sequelae of decompensated heart failure and cardiovascular collapse has historically included agents such as dopamine and dobutamine. High doses of these agents, however, lead to a variety of potential side effects including angina, ventricular arrhythmias, and excessive vasoconstriction. These agents provide stimulation to the sympathetic nervous system to help maintain cardiac output, but they do not address all of the neurohormonal pathways that are now implicated in this clinical scenario. Newer agents have been developed that lead to regulation of other neurohormonal pathways, such as the renin-angiotensin-aldosterone system. Nesiritide is one such agent that provides additional mechanisms of action along with a relatively benign side effect profile. We elected to use a combination of nesiritide combined with low-dose dopamine in the setting of acute cardiovascular collapse. We believed that the more favorable effects of nesiritide were indicated and beneficial even in the setting of hypotension and cardiovascular collapse. Nesiritide is a recombinant BNP used in the treatment of acutely decompensated heart failure. Endogenous BNP is synthesized in the ventricular myocardium in response to elevated ventricular filling pressures and ventricular stretch. BNP has a variety of physiologic actions that lead to the numerous hemodynamic changes that have been documented.2-5 BNP has the ability to counteract angiotensin II, norepinephrine, and endothelin.2 The impact of BNP's neurohormonal effects includes vasodilation and natriuresis.2 These effects result in a decrease in pulmonary capillary wedge pressure, decreased systemic vascular resistance, and an increase in cardiac output. BNP also seems to exhibit an inhibitory effect on myocardial fibrosis after a myocardial infarction.3 This is accomplished by the inhibition of the transforming growth factor-β gene, which, when expressed, regulates fibrosis and myofibroblast conversion.4 In addition, there is evidence that BNP may also effect inflammation and proliferation of smooth muscle in blood vessels.2, 4 To assess the efficacy of drug therapy, we documented hemodynamic changes during the titration of nesiritide and dopamine in this patient. Historically, documentation of these various hemodynamic parameters has been assessed via the use of a Swan-Ganz catheter; however, several drawbacks hinder the use of Swan-Ganz catheters. Insertion of the catheter itself can lead to complications. Correct placement of the catheter is also necessary for reliable readings. Patients with Swan-Ganz catheters require intensive monitoring, usually in an ICU setting. In addition, due to the invasive nature of the catheter, there is an increased risk of infection with their long-term use. Impedance cardiography provides the ability to assess hemodynamic parameters such as cardiac output, stroke volume, and systemic vascular resistance in a much less invasive manner. Several comparisons have shown similar results between the 2 methods of hemodynamic measurements.6, 7 It also provides the ability to monitor hemodynamic changes in patients in various clinical settings.8, 9 In summary, we have shown that nesiritide, in combination with low doses of dopamine, can produce favorable hemodynamic changes in an acutely decompensated individual with heart failure combined with hypotension. We have also demonstrated that impedance cardiography is an excellent tool for monitoring hemodynamic trends in the critically ill.