Only one known similar case has been previously reported in the English language literature. In 1984, Ward and Reid [1
] described a 64-year-old woman with an acute MI who had a cardiac arrest. She had ventricular tachycardia and was cardioverted to sinus bradycardia, intubated and ventilated. She received atropine, epinephrine, and calcium chloride, and had pericardiocentesis and rapid saline infusions. However, she still did not have a detectable BP. She was then started on NTG at 1 mg/minute. In three minutes, her BP was 80/60 mmHg. Several days later, her cardiac catheterization demonstrated severe coronary artery disease and a large anteroapical and septal infarction with aneurysm formation. She was eventually discharged from the hospital.
In 1990 [2
], and in 1997 [3
], we reported a case series in which the infusion of high doses of NTG resulted in rapid improvement in some patients with cardiogenic shock due to acute MI or advanced heart failure. The results are summarized in Table .
BP Response and Clinical Outcomes after High Dose NTG
High doses of NTG were used in 22 patients, including 14 patients with acute MI and eight patients with advanced HF. All patients had critically low BP measured by cuff, and 18 had an unmeasurable BP and pulse. They all had cold and mottled skin and increased central venous pressure. Eleven patients had rales in the lungs, three had pulmonary edema, and one had anasarca. The doses of NTG used in each patient, as well as the times of infusions, are listed in Table . BP became obtainable or increased in 20 of 22 patients immediately after intravenous NTG was administered. In the end, 13 patients survived.
We recently presented these data to a group of cardiology fellows, one of whom administered the bolus of NTG to our patient in this case.
According to current recommendations, intravenous NTG is contraindicated if systolic BP is below 90 mmHg. Hemodynamic properties of vasodilators, and of nitrates in particular, were extensively studied in the 1970s and 1980s, although usually not in terminal patients with no BP. In 1972, Franciosa et al. [4
] reported that intravenous sodium nitroprusside increased cardiac output and decreased wedge pressure in 15 patients with acute MI and elevated left ventricular filling pressure. Their BP was not allowed to fall below 95 mmHg, with the average drop in systolic BP at only 26 mmHg. Similar results were achieved in severe HF secondary to ischemic or dilated cardiomyopathy [5
In 1975, Chatterjee et al. [6
] described a beneficial effect of nitroprusside in 43 patients with acute MI and severe pump failure. In their series, the cardiac index increased from 1.7 to 2.2 L/min/m2
, while the left ventricular filling pressure decreased by 35%. The mean arterial pressure decreased from 83 ± 1.5 to 73 ± 1.7 mmHg. Although these patients had BP of ≤90 mm Hg by cuff, only 17 had clinical shock syndrome.
In another study evaluating incremental doses of intravenous NTG in patients with left ventricular failure the maximal hemodynamic benefit, in terms of decrease in wedge pressure and increase in cardiac index, was obtained at 160 mcg/min, which represented the highest dose tested [7
Stevenson et al. [8
] found that after-load reduction with nitroprusside in severe HF leads to smaller left ventricular end-diastolic volume and less severe mitral regurgitation, resulting in greater forward flow. The BP cutoff for nitroprusside infusion was 80 mmHg. In the emergency department, boluses of intravenous NTG ranging from 0.05 mg to 0.4 mg repeated every five minutes as needed for chest pain were used successfully to treat ischemia due to MI or unstable angina. Systolic BP was not allowed to drop below 95 mmHg [9
Recently, there has been increased interest in high dose intravenous nitrates. Cotter et al. [10
] randomized patients with pulmonary edema into cohorts receiving isosorbide dinitrate at 3 mg bolus administered intravenously every five minutes versus traditional treatment using low doses of isosorbide, furosemide, and morphine. BP was not allowed to be <90 mmHg. Mechanical ventilation was required in 13% of the high dose nitrates group and in 40% of the traditional group. MI occurred in 17% and 37%, respectively. Similar results were obtained by Phillip Levy et al. [11
], who administered up to 10 doses of NTG in intravenous boluses of 2 mg every three minutes to treat pulmonary edema with hypertension (systolic BP > 160 mmHg). In comparison with historical controls, fewer intubations, MIs, and intensive care unit admissions occurred.
One animal study has demonstrated the benefits of NTG in pigs after prolonged resuscitation. After four minutes of ventricular fibrillation and four minutes of standard CPR, pigs were randomized to the combination of epinephrine, vasopressin and NTG (7.5 mcg/kg) versus epinephrine alone. The mean coronary perfusion pressures, left ventricular, and global cerebral blood flow were significantly higher in animals who received NTG as part of the therapy. Spontaneous circulation was restored in 11 of 12 animals in the NTG group, versus 6 of 12 swine after epinephrine alone (P = NS) [12
A possible explanation for the hemodynamic benefit of NTG in our patients is increased cardiac output produced by rapid vasodilatation in a heart operating at the extreme of the Frank-Starling curve. Vasodilators in heart failure with or without acute myocardial infarction have been proven to decrease left ventricular filling pressure and systemic vascular resistance while increasing cardiac index [7
]. The more severe the failure, the more beneficial the effect of vasodilators [13
Interventricular dependence can also be a factor in cases where elevation of right ventricular pressure compromising filling of the left ventricle occurs due to severe congestion resulting from pre-existing systolic dysfunction and precipitated by ongoing ischemia. In this case, decreased preload after NTG can improve left ventricular filling and further increase cardiac output [14