Correspondence
Nitroprusside in Critically Ill Patients with Aortic Stenosis
N Engl J Med 2003; 349:811-813August 21, 2003
- Article
To the Editor:
The study by Khot et al. (May 1 issue)1 regarding the use of nitroprusside in patients with severe aortic stenosis and severe left ventricular systolic dysfunction is encouraging. However, we do not agree with the authors that nitroprusside is a safe drug. It has a very narrow therapeutic window and requires close monitoring. Nitroprusside-induced cyanide intoxication may be fatal.2 The addition of thiosulfate to nitroprusside infusion may decrease the risk of cyanide intoxication.3 Thiocyanate toxicity is another potential problem. Patients receiving a high-dose infusion (>2 to 3 μg per kilogram of body weight per minute) or patients with renal impairment should have their serum levels of thiocyanate checked after 48 to 72 hours of infusion.4 The infusion should be discontinued if the thiocyanate level is more than 10 mg per deciliter. The maximal allowable dose rate is 10 μg per kilogram per minute for no longer than 10 minutes. We believe that these recommendations should be followed closely to avoid any potential drug-related complications.
4 ReferencesPradeep K. Agarwal, M.D.
West Jefferson Medical Center, Marrero, LA 70072
pradeep.agarwal@att. net Rekha Kumari, M.D.
Louisiana State University Health Sciences Center, New Orleans, LA 701121
Khot UN ,Novaro GM ,Popovic ZB , et al. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis. N Engl J Med 2003;348:1756-1763
Full Text | Web of Science | Medline2
Hall VA ,Guest JM . Sodium nitroprusside-induced cyanide intoxication and prevention with sodium thiosulfate prophylaxis. Am J Crit Care 1992;2:19-273
Schulz V . Clinical pharmacokinetics of nitroprusside, cyanide, thiosulphate and thiocyanate. Clin Pharmacokinet 1984;9:239-251
CrossRef | Web of Science | Medline4
McKenzie CR. Hypertension. In: Carey CF, Lee HH, Woeltje KF, eds. The Washington manual of medical therapeutics. 29th ed. Philadelphia: Lippincott-Raven, 1997:61-80.
To the Editor:
Khot and colleagues demonstrate the usefulness of reducing the systemic vascular resistance with nitroprusside in patients with decompensated severe aortic stenosis. However, the authors fail to highlight the need to maintain preload when the ventricle is noncompliant. This need is all the more relevant when one is using a balanced vasodilator such as sodium nitroprusside, which affects both the systemic vascular resistance and the left ventricular end-diastolic pressure. Among similar patients treated with intravenous nitroprusside, it has been observed that the cardiac index does not increase1,2 and that the systemic vascular resistance may actually increase2 in patients with a low left ventricular end-diastolic pressure at base line or those in whom it falls by more than 10 mm Hg. In the study by Khot et al., there was a hemodynamic benefit probably because the relatively high filling pressures in patients receiving nitroprusside (mean wedge pressure, 19 mm Hg) allowed the ventricle to operate within its “preload reserve.”3 Similarly, it is likely that systemic vasodilation would be deleterious in patients with severe aortic stenosis and normal ventricular function, more because of its effect on preload than because the normal ventricle is insensitive to afterload, as the authors suggest.
3 ReferencesGanesan Karthikeyan, M.D., D.M.
All India Institute of Medical Sciences, New Delhi 110029, India
karthik_2010@hotmail.com 1
Awan NA ,DeMaria AN ,Miller RR ,Amsterdam EA ,Mason DT . Beneficial effects of nitroprusside administration on left ventricular dysfunction and myocardial ischemia in severe aortic stenosis. Am Heart J 1981;101:386-394
CrossRef | Web of Science | Medline2
Ikram H ,Low CJ ,Crozier IG ,Shirlaw T . Hemodynamic effects of nitroprusside on valvular aortic stenosis. Am J Cardiol 1992;69:361-366
CrossRef | Web of Science | Medline3
Ross J Jr . Afterload mismatch and preload reserve: a conceptual framework for the analysis of ventricular function. Prog Cardiovasc Dis 1976;18:255-264
CrossRef | Web of Science | Medline
To the Editor:
Patients were enrolled in the study by Khot et al. regardless of whether they had coexisting coronary artery disease. Nitroprusside was infused in patients with left ventricular dysfunction and aortic stenosis in order to assess the primary end point of the cardiac index. However, the authors mention two clinical episodes of cardiac ischemia: one episode of chest pain in a patient during the infusion period and a case of refractory unstable angina that was not amenable to coronary revascularization. It is known that nitroprusside may exacerbate cardiac ischemia by means of a “steal” mechanism.1 In view of this potential detrimental effect, assessment of cardiac troponin as a measure of myocardial damage would have been warranted.
Any improvement in the cardiac index provided by nitroprusside in this setting may have caused some damage to myocardial tissue. Perhaps a different agent, such as nitroglycerin, would be a more suitable agent in the setting of coronary artery disease.2
2 ReferencesAndrew Gogbashian, M.B., B.S.
Hammersmith Hospital, London W12 0HS, United Kingdom1
Ihlen H ,Myhre E ,Opstad P . Evaluation of potential adverse effects of sodium nitroprusside during pacing-induced myocardial ischemia in man. Eur Heart J 1984;5:834-841
Web of Science | Medline2
Mann T ,Cohn PF ,Holman LB ,Green LH ,Markis JE ,Phillips DA . Effect of nitroprusside on regional myocardial blood flow in coronary artery disease: results in 25 patients and comparison with nitroglycerin. Circulation 1978;57:732-738
Web of Science | Medline
Author/Editor Response
Our experience does not support the concern of Drs. Agarwal and Kumari regarding cyanide and thiocyanate toxicity. In fact, the reference they cite reports data from the Food and Drug Administration, which documented 25 deaths associated with nitroprusside administration over a 15-year period. Deaths that are clearly related to cyanide toxicity involve infusion rates that are much higher than those conventionally used today.1 We do not routinely administer thiosulfate, since it may paradoxically increase the incidence of thiocyanate toxicity.1 We routinely measure thiocyanate levels after three days of nitroprusside but have found elevated levels and clinical toxic effects to be exceedingly rare, even if there is abnormal renal function.1,2 Therefore, we believe that nitroprusside is safe.
Limiting the administration of nitroprusside to patients without coronary artery disease would unnecessarily exclude many patients who could derive a clear benefit from nitroprusside. The routine measurement of troponin, as suggested by Dr. Gogbashian, would be confounded by the numerous patients who presented after a recent myocardial infarction. Nitroglycerin predominantly reduces the preload and has limited ability to improve cardiac output.3 The development of tachyphylaxis with continuous infusion further limits its use.
The report cited by Dr. Karthikeyan showed a failure of the cardiac index to increase in patients with a normal ejection fraction, who were specifically not included in our study. However, the results in patients with a depressed ejection fraction were similar to those in our study, with the cardiac index increasing with nitroprusside use. In addition, Dr. Karthikeyan suggests that our results apply only to patients with an elevated left ventricular end-diastolic pressure. If this were true, then a subgroup of our patients who had a low base-line left ventricular end-diastolic pressure or a substantial decrease in the left ventricular end-diastolic pressure (>10 mm Hg) with nitroprusside should have had a decrease in the cardiac index. However, as shown in Figure 2 of our article, all patients had an increase in the cardiac index, despite wide variations in base-line preload levels and change in preload with nitroprusside. Stevenson and Tillisch have similarly shown that increases in the cardiac output with nitroprusside can be maintained even with a normal preload in the failing heart.4
We wish to underscore the importance of continuous electrocardiographic and invasive hemodynamic monitoring in an intensive care unit in order to achieve our results. When it is administered in this setting, nitroprusside rapidly and safely normalizes the cardiac output and can be used effectively as a bridge to either aortic-valve replacement or oral vasodilator therapy.
4 ReferencesUmesh N. Khot, M.D.
Indiana Heart Physicians, Beech Grove, IN 46107
khot@cvresearch.net Gian M. Novaro, M.D.
Cleveland Clinic Florida, Weston, FL 33331Gary S. Francis, M.D.
Cleveland Clinic Foundation, Cleveland, OH 441951
Friederich JA ,Butterworth JF IV . Sodium nitroprusside: twenty years and counting. Anesth Analg 1995;81:152-162
CrossRef | Web of Science | Medline2
Schulz V . Clinical pharmacokinetics of nitroprusside, cyanide, thiosulphate and thiocyanate. Clin Pharmacokinet 1984;9:239-251
CrossRef | Web of Science | Medline3
Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF)
CrossRef | Web of Science4
Stevenson LW ,Tillisch JH . Maintenance of cardiac output with normal filling pressures in patients with dilated heart failure. Circulation 1986;74:1303-1308
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
J. David Spence. (2007) New treatment options for hypertension during acute ischemic or hemorrhagic stroke. Current Treatment Options in Cardiovascular Medicine 9:3, 242-246
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