Users Online: 229 Home Print this page Email this page Small font sizeDefault font sizeIncrease font size  
Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Login 

RSACP wishes to inform that it shall be discontinuing the dispatch of print copy of JOACP to it's Life members. The print copy of JOACP will be posted only to those life members who send us a written confirmation for continuation of print copy.
Kindly email your affirmation for print copies to [email protected] preferably by 30th June 2019.


Table of Contents
Year : 2014  |  Volume : 30  |  Issue : 4  |  Page : 462-471

Sodium nitroprusside in 2014: A clinical concepts review

Department of Anesthesiology, University of Minnesota, Minneapolis, MN 55455, USA

Date of Web Publication14-Oct-2014

Correspondence Address:
Kumar G Belani
Department of Anesthesiology, University of Minnesota, MMC 8294, 420 Delaware Street SE, Minneapolis, MN 55455
Login to access the Email id

Source of Support: Work related to the new cyanide antidote was supported by Grant NIH NINDS/5U01NS058087., Conflict of Interest: None

DOI: 10.4103/0970-9185.142799

Rights and Permissions

Sodium nitroprusside has been used in clinical practice as an arterial and venous vasodilator for 40 years. This prodrug reacts with physiologic sulfhydryl groups to release nitric oxide, causing rapid vasodilation, and acutely lowering blood pressure. It is used clinically in cardiac surgery, hypertensive crises, heart failure, vascular surgery, pediatric surgery, and other acute hemodynamic applications. In some practices, newer agents have replaced nitroprusside, either because they are more effective or because they have a more favorable side-effect profile. However, valid and adequately-powered efficacy studies are sparse and do not identify a superior agent for all indications. The cyanide anion release concurrent with nitroprusside administration is associated with potential cyanide accumulation and severe toxicity. Agents to ameliorate the untoward effects of cyanide are limited by various problems in their practicality and effectiveness. A new orally bioavailable antidote is sodium sulfanegen, which shows promise in reversing this toxicity. The unique effectiveness of nitroprusside as a titratable agent capable of rapid blood pressure control will likely maintain its utilization in clinical practice for the foreseeable future. Additional research will refine and perhaps expand indications for nitroprusside, while parallel investigation continues to develop effective antidotes for cyanide poisoning.

Keywords: Antihypertensives, cyanide, pharmacology, sodium nitroprusside, toxicity

How to cite this article:
Hottinger DG, Beebe DS, Kozhimannil T, Prielipp RC, Belani KG. Sodium nitroprusside in 2014: A clinical concepts review . J Anaesthesiol Clin Pharmacol 2014;30:462-71

How to cite this URL:
Hottinger DG, Beebe DS, Kozhimannil T, Prielipp RC, Belani KG. Sodium nitroprusside in 2014: A clinical concepts review . J Anaesthesiol Clin Pharmacol [serial online] 2014 [cited 2021 Feb 26];30:462-71. Available from:

  Introduction and History Top

Sodium nitroprusside (SNP) is a well-known arterial and venous vasodilator used in clinical practice to lower blood pressure. Initially discovered in 1849 by Playfair, [1] SNP's first reported use in a patient was by Johnson in 1922. [2] Its safety and efficacy in lowering blood pressure when given intravenously in severely hypertensive patients was established in 1955. [3] After its successful use as an intraoperative antihypertensive in 1970, [4] it quickly gained acceptance as a fast-acting agent useful to reduce intraoperative hypertension, induce hypotension to minimize surgical blood loss, and decrease afterload and improve cardiac output in heart failure. It has been used clinically in cardiac surgery, hypertensive crises, heart failure, vascular surgery, pediatric surgery, and other acute applications.

However, reports began to surface associating nitroprusside and cyanide toxicity, [5],[6],[7],[8] with the food and drug administration (FDA) issuing new labeling emphasizing this risk in 1991. [9] In some practices newer agents [including nitroglycerin, calcium channel blockers, β-blockers, and dopaminergic agonists, [Table 1] replaced SNP, either because they were recognized to be more arterial selective, or because of a more favorable side-effect profile. Despite the risks, nitroprusside has continued to be used in many of the above settings and others for its potent and fast-acting vasodilatory properties. In addition, the ongoing threat of cyanide as a chemical warfare agent in bioterrorism continues to fuel research to reverse or prevent cyanide poisoning, and thus by association retains an interest in nitroprusside.
Table 1: Comparison of systemic vasodilators available for the control of perioperative hypertension

Click here to view

The last prominent review of SNP was by Friederich and Butterworth in 1995. [10] Since then, new research has deepened the understanding of its mechanism of action, refined its clinical application by comparing it to newer vasodilators, further elaborated its adverse effects and safety profile, and offered promise for reversing its significant potential toxicity.

Now 40 years since nitroprusside's widespread adoption and almost 20 years since its last thorough review, we summarize the new salient developments for this agent. Our goal is to provide clinicians with a comprehensive, updated benefit-to-risk understanding of the current use of nitroprusside in clinical practice. In addition, we provide newer experimental data of an antidote for cyanide toxicity, which may lead to an expanded role of nitroprusside in the future.

  Mechanism of Action and Hemodynamic Effects Top

Sodium nitroprusside is a water-soluble sodium salt comprised of Fe 2+ complexed with nitric oxide (NO) and five cyanide anions [Figure 1]. In the body it functions as a prodrug, reacting with sulfhydryl groups on erythrocytes, albumin, and other proteins to release NO. [11] NO, or endothelium derived relaxing factor, stimulates guanyl cyclase to produce cyclic GMP, sequestering calcium and inhibiting cellular contraction. [12] At the tissue level, these effects of NO result in reduced vascular tone in muscular conduit arteries. [13] NO released from nitroprusside decreases cerebral vascular resistance, and in a canine study it has been shown to impair brain and myocardial tissue oxygenation due to increase in arterial-venous shunting. [14] It decreases coronary flow reserve, which is the basis for the theory that nitroprusside can cause coronary steal syndrome, discussed further below. [15]
Figure 1: The sodium nitroprusside molecule is a sodium salt consisting of Fe complexed with five cyanide anions

Click here to view

The role of NO in the coagulation system and platelet function raised the concern that nitroprusside and other NO releasing drugs may affect coagulation, at least in theory. [16] A few studies showed the ability of nitroprusside to inhibit platelet aggregation in vitro[17] and in vivo. [18] One study showed increased intraoperative blood loss in spinal surgery with nitroprusside compared with nicardipine, but the authors did not believe that this was necessarily due to any effect on platelets but rather might be explained by increased venous congestion. [19] The clinical significance, if any, of nitroprusside administration on bleeding remains unproven.

Globally, the net hemodynamic effect of nitroprusside is to cause arterial and venous dilatation, reduce afterload, decrease ventricular filling pressures, lower the systemic blood pressure, and increase cardiac output, without significant lowering of the heart rate. These properties, together with nitroprusside's rapid onset and ability to be titrated to a target blood pressure, make the agent highly effective in situations where rapid blood pressure lowering is indicated.

  Clinical Use, Efficacy, and Comparative Advantages of Nitroprusside Top

Dosing and administration

Sodium nitroprusside is typically started as an intravenous infusion of 0.5 μg/kg/min and titrated to effect, with a maximum dose of 10 μg/kg/min (for short periods to establish blood pressure control). Limited data about pediatric dosing suggests that infusion rates should remain below 2 μg/kg/min, and reserve higher doses for short periods to establish urgent blood pressure control. [20],[21] SNP acts within minutes and is effective in clinical situations where urgent lowering of blood pressure is needed. However, this means that it requires vigilant monitoring to avoid the rapid onset of hypo-perfusion or potentially life-threatening hypotension. These properties have traditionally restricted its use to short duration therapy in the operating room, ICU, cardiac care unit, or other areas where continuous close monitoring by experienced providers is available. It must be protected from light to prevent degradation and the subsequent rapid cyanide anion release upon administration. [22] Routine monitoring of cyanide levels may not be necessary.

Cardiac surgery

Perioperative hypertension in cardiac surgery is common, reported in 15-50% of patients depending on the type of surgery performed, [23],[24] and is a risk factor for adverse outcomes after surgery. [25] Managing intraoperative hypertension is important because the blood pressure lability in hypertensive patients, due to impaired autoregulation of organ blood flow, confers on them a predilection for hypo-perfusion and subsequent ischemic events and end organ damage. [26] It can also produce vascular anastomotic disruption. Indeed, greater blood pressure variability has been associated with increased 30-day perioperative mortality in cardiac surgery patients. [27] The recommendation is to optimize blood pressure at least 6 weeks prior to noncardiac surgery; this may also be a reasonable strategy in cardiac surgery. [28] The ideal intraoperative agent could be easily and rapidly titrated to effect with minimal swings in blood pressure or risk of hypotension.

Historically, nitroprusside has been a favored agent to control blood pressure intraoperatively, although it carries risk for hypotension in addition to toxicity. Once its efficacy during and after cardiac surgery was established, [29],[30] it became the "gold standard" against which newer agents were studied for efficacy and comparative advantages. Nitroglycerin was compared to nitroprusside in a randomized, open-label crossover study of 17 patients by Flaherty et al. [31] While all patients responded to nitroprusside, a subset of patients achieved with nitroglycerin only 50% of the blood pressure reduction achieved with nitroprusside. The time to achieve blood pressure control was not reported. Pulmonary gas exchange parameters were improved during administration of nitroglycerin, while nitroprusside worsened these variables. No significant adverse effects were reported, but nitroprusside was noted to cause tachycardia in four patients.

The B-blockers esmolol and labetalol were compared with nitroprusside in postoperative cardiac surgical patients. [32] Labetalol lowered blood pressure in magnitude similar to nitroprusside, but over a much slower timeframe and with a significantly different hemodynamic profile. Labetalol lowered the heart rate and cardiac index, while central venous pressure was increased. By comparison, patients treated with nitroprusside had significantly greater reductions in diastolic blood pressure (DBP) and mean arterial pressure, and an increased heart rate, stroke volume, and cardiac index. The authors speculated that the higher DBP and lower heart rate might improve coronary perfusion and reduce myocardial oxygen demand in patients treated with labetalol. No complications were noted in either group. Gray et al. compared esmolol with SNP in postcardiac surgical patients and observed similar results. SNP lowered DBP more than esmolol and caused an increase in heart rate. There was a nonsignificant trend of quicker blood pressure control with SNP over esmolol (21 ± 15 vs. 29 ± 14 min, respectively). [33]

The calcium channel blockers nicardipine and clevidipine have been compared with nitroprusside. Nicardipine was compared with nitroprusside by Halpern et al. in cardiac and noncardiac surgical patients. [34] Nicardipine controlled blood pressure more quickly and with less adverse effects, which included tachycardia and hypotension that resulted in discontinuation of the drug in 6 patients. None were discontinued from the nicardipine group. Both drugs exhibited similar effects on circulatory variables. Nitroprusside was shown by Aronson et al. to be inferior to clevidipine in controlling systolic blood pressure after cardiac surgery. [35] They observed greater blood pressure variability and increased mortality with nitroprusside compared to clevidipine. An explanation for this may be because longstanding hypertensive patients with stiff ventricles are more susceptible to reductions in preload from nitroprusside, a direct arterial and venous vasodilator. On the other hand, clevidipine primarily dilates arterial smooth muscle, preserving preload.

Taken together, these studies do not identify a preferred agent in cardiac surgery. In one study, clevidipine appeared superior as a first line agent because it kept blood pressure within predefined ranges better than nitroprusside. However, mortality differences between clevidipine and nitroprusside were explained by sicker patients in nitroprusside patients. In other studies, nitroprusside controlled blood pressure more quickly and was often needed as a second line agent when other drugs failed. While nitroprusside may produce reflex tachycardia in some patients, there were no cases where this was directly attributed to cyanide toxicity.

Hypertensive crises

Hypertensive crises are elevations in systolic blood pressure ≥180 mmHg or DBP ≥110 mmHg and are divided into hypertensive urgencies or hypertensive emergencies, with the latter having clinical evidence of end organ damage. [36] Blood pressure in hypertensive urgencies should be lowered over 24-48 h, while in hypertensive emergencies it should be lowered within minutes to hours. These events have many etiologies and present within a variety of clinical syndromes, and the choice of treatment depends on the target organ affected. [37]

Despite a paucity of definitive comparative, prospective, randomized controlled trials, newer agents have replaced SNP in many of these contexts because of evidence of clinical equipoise, less stringent monitoring requirements, and more favorable side effect profiles. In an analysis of the Special Tertiary Admissions Test registry, investigators found that the most common parental agent given for hypertensive crises in an emergency room or Intensive Care Unit (ICU) setting was labetalol (48%), followed by nicardipine (15%), hydralazine (15%), and nitroprusside (13%). Treatment with nitroprusside and nitroglycerin were associated with a higher mortality, but this was of borderline significance and likely confounded by bias with regard to choice of agent. [38] One study by Immink et al. compared labetalol with nitroprusside in their effects on cerebral hemodynamics in the treatment of malignant hypertension. Nitroprusside preferentially lowered systemic vascular resistance more than cerebral vascular resistance, causing lower middle cerebral blood velocities, presumably by shunting of blood to the low resistance, dilated systemic vascular bed. Labetalol did not produce these effects. [39] Other small, prospective trials have compared nitroprusside to fenoldopam [40] and nicardipine [41],[42] with results of similar efficacy and little observable differences in side effects. SNP continues to be used to lower blood pressure in acute aortic dissection and acute pulmonary edema, although the recommendation is to use it only when more preferred intravenous agents are unavailable. [37]

The vasodilatory properties of nitroprusside spurred interest in its use for hypertensive crises associated with cerebrovascular accidents, especially subarachnoid and intracerebral hemorrhage. Early animal studies concluded that nitroprusside could cause vasodilation, prevent vasospasm, and maintain cerebral blood flow immediately following subarachnoid hemorrhage. [43],[44],[45] One study showed reversal of cerebral vasospasm in humans after nitroprusside administration in three patients who suffered a subarachnoid hemorrhage. [46] Subsequent work conflicted with these results, however, and did not show any increase in cerebral blood flow. [47],[48],[49] The current American Heart Association guidelines recommend using nitroprusside, labetalol, or nicardipine to treat acute hypertension to a target of a systolic blood pressure below 180 mmHg in patients with intracerebral hemorrhage. [50] There is some evidence to support the use of nicardipine over nitroprusside in this setting, as it was associated with lower in-hospital mortality. [51]

Heart failure

Sodium nitroprusside was first studied as therapy for heart failure in the 1970's. Since then many small studies have shown it to reduce afterload and improve left ventricular filling and cardiac output in acute decompensated heart failure, reviewed thoroughly by Opasich et al. [52] The 2010 Heart Failure Society of America comprehensive heart failure practice guidelines recommend nitroprusside among other vasodilators in the management of acute decompensated heart failure (Grade B recommendation). [53] Nitroprusside infusion should be monitored while its dosing titrated to appropriate clinical effect, observing for hypotension and signs of cyanide toxicity. These requirements have somewhat restricted its use, although at least one study found that with experienced providers, chronic heart failure patients who received low dose nitroprusside therapy showed reduced mortality and adverse outcomes were rare. [54] Another study showed that intermittent low dose nitroprusside infusion reduced mortality in patients with advanced heart failure awaiting transplantation. [55] It has been shown to benefit critically ill patients with left ventricular dysfunction and aortic stenosis as a bridge to valve replacement or oral vasodilator therapy. [56] Elkayam et al. provide an excellent review of the use of nitroprusside and vasodilator therapy in the management of acute decompensated heart failure. [57]

Aortic surgery

Cross-clamping of the aorta is commonly used to repair aortic aneurysms, coarctations, and traumatic injury, among other pathologies. This procedure can have dramatic effects on cardiovascular physiology and regional hemodynamics and oxygenation due to often severe hypertension proximal to the clamping and hypo-perfusion distally, presenting challenges for the anesthesiologist. [58] While outcomes after open and endovascular abdominal aorta surgery have improved dramatically, [59] the survival rate and complications associated with thoracic cross-clamping remain poor. [60]

Few studies directly compare nitroprusside with other intravenous antihypertensives and their effects on surgical outcomes in aortic surgery. Early animal studies showed SNP to be associated with a poorer response of multiple variables in the setting of cross-clamping when compared to other antihypertensive agents or controls, including increased cerebral spinal fluid pressure, [61] lower spinal cord perfusion pressure, and increased neurologic injury [62],[63],[64] and mortality. [65] In one of the few head to head comparisons of nitroprusside and another antihypertensive agent, fenoldopam, during cross-clamping, no differences were found in intraoperative hemodynamic variables or renal indices. Patients treated with nitroprusside had a higher average heart rate precross clamp. [66] Another study showed decreased mixed venous oxygen saturation in patients controlled with nitroprusside versus amrinone during cross-clamping, but no difference in hemodynamic control. [67] In both studies, the complication rate was the same between nitroprusside and the alternative treatment. Further research is necessary to elucidate a preferred agent in aortic surgery in adults.

Pediatric patients undergoing aortic surgery are particularly susceptible to changes in cerebral oxygenation induced by nitroprusside. One study showed decreased cerebral oxygenation after administration of nitroprusside in two children undergoing cross-clamping for coarctation repair. This decrease was over and above the decrease attributable directly to cross-clamping, as esmolol and ionotrope administration did not result in a similar decrease. [68] Another study showed no differences in cerebral venous oxygenation when nitroprusside was compared with nitroglycerin or sevoflurane. [69] Current practices are not well-described, but they favor control of perioperative hypertension in pediatric aortic surgery with esmolol and nitroprusside or nitroglycerin intravenously. [70]

Emerging applications

Nitroprusside continues to be applied in new ways. In cardiology, the "no-reflow" phenomenon is defined as the lack of blood flow following an intervention to restore patency to coronary vessels. [71] It is estimated to occur in 3.2-4.8% of all percutaneous coronary interventions, more after myocardial infarction, and adversely impacts outcomes. [72] Vasodilation with nitroprusside has offered promise to both prevent and treat this potential complication. [73] In a small, randomized, placebo-controlled trial, nitroprusside was recently shown to improve symptoms of schizophrenia after a single administration. [74] The proposed mechanism for this effect is based on the derangements in cerebral NO regulation observed in schizophrenic patients and nitroprusside's ability to increase NO production in the brain. This NO releasing property of nitroprusside has been shown to increase apoptosis in gastric cancer cells. [75] [Table 1] compares the pharmacological profile of SNP to other antihypertensives currently available for the acute control of perioperative hypertension.

  Metabolism, Safety, and Toxicity Top

Nitroprusside reacts with oxyhemoglobin to form methemoglobin and release cyanide anions in vivo. [8],[76] These ions have multiple possible fates [Figure 2]:
Figure 2: The possible fates of cyanide anion in the body

Click here to view

  1. They may react again with methemoglobin to form cyanomethemoglobin and accumulate in erythrocytes.
  2. They may be transported to the liver where they react with thiosulfate and cobalamin to form thiocyanate, which is excreted in the kidneys.
  3. They may bind to tissue cytochrome oxidase, inhibiting oxidative phosphorylation. [77]

It is this final pathway that produces "cyanide toxicity," which has been well-documented in clinical cases and animal studies. [5],[6],[7],[78],[79],[80] Further research has attempted to characterize these toxic effects in specific tissues. Nitroprusside is toxic to cerebral endothelial cells, [81] hepatocytes, [82] and neural cell lines, [83] generating reactive oxygen species and inducing apoptotic cell death. It is estimated that adults can detoxify 50 mg of nitroprusside (one vial of the traditional commercial formulation), but infusion rates higher than 2 μg/kg/min may lead to toxic cyanide accumulations. [8]

Assessment of cyanide toxicity can be difficult if lab assays measure whole blood cyanide concentrations rather than serum cyanide concentrations, which are better correlated with cyanide toxicity. [84] Elevated lactate concentrations are an excellent surrogate [Figure 3] and serve as a marker of cyanide toxicity in patients; they can be used to support the diagnosis. [85] Unfortunately, many of the clinical signs of cyanide toxicity, such as restlessness, agitation, and sinus tachycardia are difficult to evaluate intraoperatively and lead to a misdiagnosis.
Figure 3: Note the progressive increase in serum lactate levels with the infusion of sodium cyanide in a pig model of cyanide toxicity[96]

Click here to view

Cheung et al. showed that the plasma free hemoglobin concentration correlated positively with time on cardiac bypass and the cyanide anion concentration, suggesting that prolonged exposure to bypass increased a patient's risk for cyanide toxicity because of increased erythrocyte shearing and intracellular cyanide release. [86] Therefore, nitroprusside should be replaced in this setting with newer drugs.

In addition to cyanide toxicity, the concept of "coronary steal" associated with nitroprusside has long been reported. Mann et al. compared regional myocardial blood flow (RMBF) after administration of nitroprusside and nitroglycerin in normal patients and patients with coronary artery disease (CAD). [15] They found some evidence of reduced RMBF in those patients receiving nitroprusside with well-developed collaterals compared to an increase in RMBF in similar patients treated with nitroglycerin. Left ventricular end diastolic pressure was not measured in either group, which may have influenced the myocardial blood flow. In addition, nitroprusside administration was noted to result in a lower average MAP than that achieved with nitroglycerin, further confounding the results because DBP provides the driving force for coronary perfusion pressure. It is postulated that these differences are due to nitroglycerin's preferential effect on larger conductance vessels, while nitroprusside dilates smaller resistance vessels, creating a low pressure system distal to occluded vessels that diverts critical pressure-dependent flow from ischemic areas. [87] The clinical significance of these observations is uncertain, and the true incidence of clinically significant coronary steal remains unknown. The more important clinical consideration in patients with CAD on a nitrovasodilator may be to prevent hypotension, which may be more easily achievable with alternative therapies. [35]

The use of nitroprusside has been associated with increased intracranial pressure (ICP). [88],[89] The mechanism for this is due to increased cerebral blood flow and resultant increased blood volume in the setting of impaired autoregulation attributable to nitroprusside. [90] Caution should be taken in patients with intracranial mass lesions, encephalopathy or other reasons for an elevated ICP.

  Antidotes: Mechanism and Clinical Application Top

Knowledge of the metabolic pathways of nitroprusside and mechanism of cyanide toxicity has spurred the investigation of potential agents to reverse or prevent this. A review by Reade et al. of available evidence found both sodium thiosulfate and hydroxocobalamin equally effective in reversal of cyanide poisoning with no significant adverse effects to either. [91] These medicines work by increasing the thiosulfate or hydroxocobalamin substrate normally present in serum to buffer against rising cyanide concentrations and minimize its reaction with mitochondrial cytochromes. The thiosulfate-associated antidotes depend on the enzyme rhodanese to catalyze the conversion of cyanide to the less toxic thiocyanate [Figure 2]. However, since this enzyme is predominantly localized to the liver and red blood cells, important tissues such as the brain and heart remain unprotected. [92] Patients with conditions such as Leber's hereditary optic neuropathy lack adequate rhodanase activity and are especially vulnerable to nitroprusside toxicity. Hydroxocobalamin-based therapies work by binding and trapping cyanide anions as cyanocobalamin which is excreted in urine, but clinical results have been mixed. [93] Only the combination of sodium thiosulfate and sodium nitrite is currently approved by the FDA for treatment of cyanide poisoning. In addition, these treatments can be difficult or expensive to administer or have serious side effects.

Recently however, a new oral cyanide antidote, sulfanegen sodium, a prodrug of 3-mercaptopyruvate, has been developed. [92] It is readily formed from commercially available starting materials [Figure 4] and has additional advantages in that it is available orally and is effective when administered prophylactically up to 1 h before cyanide exposure. The sulfanegen sodium's dimer dissociates nonenzematically in physiologic conditions and pH of 7.4-3-mercaptopyruvate, which through further metabolism ultimately captures and converts cyanide anions into SCN, excreted in the kidneys. The prodrug was shown in initial experiments to be effective in reversing sub lethal cyanide toxicity in murine and rabbit models. [92],[94],[95]
Figure 4: Sulfanegen sodium, prodrug for 3-mercaptopyruvate, is formed from 3-bromopyruvic acid, sodium hydrogen sulfide, and methanol[96]

Click here to view

Further experiments have characterized the effect of sulfanegen sodium in juvenile pigs. [96] Lethal injections of SNP were administered, after which either sulfanegen sodium antidote or placebo was given. In the treatment groups, the antidote normalized blood lactate levels and hemodynamic variables, while pigs receiving placebo decompensated and succumbed [Table 2]. Additional research is underway to determine whether this drug may successfully reverse cyanide toxicity in humans.
Table 2: Results of hemodynamic changes observed during SNP infusion, followed either by placebo or sulfanegen sodium given 2 h after SNP infusion[96]

Click here to view

  Summary Top

Over 150 years since its discovery and 40 years since its widespread adoption into clinical practice, SNP remains a frequently-used vasodilator in the management of acute and severe systemic hypertension and additional applications (such as treatment of cerebral vasospasm) still in development. Due to its ubiquitous availability and widespread use, clinicians must be cognizant about its high potency and potential toxicities, while using this drug, including cyanide toxicity, altered blood flow distribution to and within organs, increased pulmonary shunting, and excessive hypotension. Caution dictates heightened vigilance for worsening confusion, drug tachyphylaxis, and metabolic acidosis with a base deficit - all indicating possible cyanide toxicity. Future antidotes appear to hold promise and may be available for cyanide toxicity; there are no current data about their human efficacy or safety. Therefore, practitioners must balance these factors, while recognizing alternatives that are newer, possibly safer, but usually more expensive. Future prospective, randomized controlled trials that directly compare nitroprusside with other potent vasodilators should facilitate better treatment guidelines. In addition, further research is necessary to develop better ways to detect, prevent, and reverse cyanide toxicity.

  References Top

Playfair, L. On the nitroprusside: A new class of salts. Philos Trans R Soc Lond 1849;139:41.  Back to cited text no. 1
Johnson C. Mechanisms of actions and toxicity of nitroprusside. Exp Biol Med 1928;26:2.  Back to cited text no. 2
Page IH, Corcoran AC, Dustan HP, Koppanyi T. Cardiovascular actions of sodium nitroprusside in animals and hypertensive patients. Circulation 1955;11:188-98.  Back to cited text no. 3
Taylor TH, Styles M, Lamming AJ. Sodium nitroprusside as a hypotensive agent in general anaesthesia. Br J Anaesth 1970;42:859-64.  Back to cited text no. 4
Amaranath L, Kellermeyer WF Jr. Tachyphylaxis to sodium nitroprusside. Anesthesiology 1976;44:345-8.  Back to cited text no. 5
Davies DW, Kadar D, Steward DJ, Munro IR. A sudden death associated with the use of sodium nitroprusside for induction of hypotension during anaesthesia. Can Anaesth Soc J 1975;22:547-52.  Back to cited text no. 6
Cyanide intoxication from sodium nitroprusside in anesthesia. Med Lett Drugs Ther 1976;18:68.  Back to cited text no. 7
Vesey CJ, Cole PV, Simpson PJ. Cyanide and thiocyanate concentrations following sodium nitroprusside infusion in man. Br J Anaesth 1976;48:651-60.  Back to cited text no. 8
Nightingale SL. From the food and drug administration. JAMA 1991;265:847.  Back to cited text no. 9
Friederich JA, Butterworth JF 4 th . Sodium nitroprusside: Twenty years and counting. Anesth Analg 1995;81:152-62.  Back to cited text no. 10
Ivankovich AD, Miletich DJ, Tinker JH. Sodium nitroprusside: Metabolism and general considerations. Int Anesthesiol Clin 1978;16:1-29.  Back to cited text no. 11
Levy JH. Management of systemic and pulmonary hypertension. Tex Heart Inst J 2005;32:467-71.  Back to cited text no. 12
Fok H, Jiang B, Clapp B, Chowienczyk P. Regulation of vascular tone and pulse wave velocity in human muscular conduit arteries: Selective effects of nitric oxide donors to dilate muscular arteries relative to resistance vessels. Hypertension 2012;60:1220-5.  Back to cited text no. 13
Hoffman WE, Albrecht RF 2 nd , Jonjev ZS. Sodium nitroprusside-induced, but not desflurane-induced, hypotension decreases myocardial tissue oxygenation in dogs anesthetized with 8% desflurane. J Cardiothorac Vasc Anesth 2002;16:286-9.  Back to cited text no. 14
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;57:732-8.  Back to cited text no. 15
Clark D 3 rd , Tesseneer S, Tribble CG. Nitroglycerin and sodium nitroprusside: Potential contributors to postoperative bleeding? Heart Surg Forum 2012;15:E92-6.  Back to cited text no. 16
Hines R, Barash PG. Infusion of sodium nitroprusside induces platelet dysfunction in vitro. Anesthesiology 1989;70:611-5.  Back to cited text no. 17
Butterworth RJ, Cluckie A, Jackson SH, Buxton-Thomas M, Bath PM. Pathophysiological assessment of nitric oxide (given as sodium nitroprusside) in acute ischaemic stroke. Cerebrovasc Dis 1998;8:158-65.  Back to cited text no. 18
Hersey SL, O'Dell NE, Lowe S, Rasmussen G, Tobias JD, Deshpande JK, et al. Nicardipine versus nitroprusside for controlled hypotension during spinal surgery in adolescents. Anesth Analg 1997;84:1239-44.  Back to cited text no. 19
Moffett BS, Price JF. Evaluation of sodium nitroprusside toxicity in pediatric cardiac surgical patients. Ann Pharmacother 2008;42:1600-4.  Back to cited text no. 20
Thomas C, Svehla L, Moffett BS. Sodium-nitroprusside-induced cyanide toxicity in pediatric patients. Expert Opin Drug Saf 2009;8:599-602.  Back to cited text no. 21
Bisset WI, Butler AR, Glidewell C, Reglinski J. Sodium nitroprusside and cyanide release: Reasons for re-appraisal. Br J Anaesth 1981;53:1015-8.  Back to cited text no. 22
Estafanous FG, Tarazi RC. Systemic arterial hypertension associated with cardiac surgery. Am J Cardiol 1980;46:685-94.  Back to cited text no. 23
Cooper TJ, Clutton-Brock TH, Jones SN, Tinker J, Treasure T. Factors relating to the development of hypertension after cardiopulmonary bypass. Br Heart J 1985;54:91-5.  Back to cited text no. 24
Roach GW, Kanchuger M, Mangano CM, Newman M, Nussmeier N, Wolman R, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335:1857-63.  Back to cited text no. 25
Aronson S, Fontes ML, Miao Y, Mangano DT, Investigators of the Multicenter Study of Perioperative Ischemia Research Group, Ischemia Research and Education Foundation. Risk index for perioperative renal dysfunction/failure: Critical dependence on pulse pressure hypertension. Circulation 2007;115:733-42.  Back to cited text no. 26
Aronson S, Dyke CM, Levy JH, Cheung AT, Lumb PD, Avery EG, et al. Does perioperative systolic blood pressure variability predict mortality after cardiac surgery? An exploratory analysis of the ECLIPSE trials. Anesth Analg 2011;113:19-30.  Back to cited text no. 27
Eagle KA, Berger PB, Calkins H, Chaitman BR, Ewy GA, Fleischmann KE, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery - Executive summary a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation 2002;105:1257-67.  Back to cited text no. 28
Lappas DG, Lowenstein E, Waller J, Fahmy NR, Daggett WM. Hemodynamic effects of nitroprusside infusion during coronary artery operation in man. Circulation 1976;54:III4-10.  Back to cited text no. 29
Stinson EB, Holloway EL, Derby G, Oyer PE, Hollingsworth J, Griepp RB, et al. Comparative hemodynamic responses to chlorpromazine, nitroprusside, nitroglycerin, and trimethaphan immediately after open-heart operations. Circulation 1975;52:I26-33.  Back to cited text no. 30
Flaherty JT, Magee PA, Gardner TL, Potter A, MacAllister NP. Comparison of intravenous nitroglycerin and sodium nitroprusside for treatment of acute hypertension developing after coronary artery bypass surgery. Circulation 1982;65:1072-7.  Back to cited text no. 31
Cruise CJ, Skrobik Y, Webster RE, Marquez-Julio A, David TE. Intravenous labetalol versus sodium nitroprusside for treatment of hypertension postcoronary bypass surgery. Anesthesiology 1989;71:835-9.  Back to cited text no. 32
Gray RJ, Bateman TM, Czer LS, Conklin C, Matloff JM. Comparison of esmolol and nitroprusside for acute post-cardiac surgical hypertension. Am J Cardiol 1987;59:887-91.  Back to cited text no. 33
Halpern NA, Goldberg M, Neely C, Sladen RN, Goldberg JS, Floyd J, et al. Postoperative hypertension: A multicenter, prospective, randomized comparison between intravenous nicardipine and sodium nitroprusside. Crit Care Med 1992;20:1637-43.  Back to cited text no. 34
Aronson S, Dyke CM, Stierer KA, Levy JH, Cheung AT, Lumb PD, et al. The ECLIPSE trials: Comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg 2008;107:1110-21.  Back to cited text no. 35
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206-52.  Back to cited text no. 36
Marik PE, Varon J. Hypertensive crises: Challenges and management. Chest 2007;131:1949-62.  Back to cited text no. 37
Mayer SA, Kurtz P, Wyman A, Sung GY, Multz AS, Varon J, et al. Clinical practices, complications, and mortality in neurological patients with acute severe hypertension: The Studying the Treatment of Acute hyperTension registry. Crit Care Med 2011;39:2330-6.  Back to cited text no. 38
Immink RV, van den Born BJ, van Montfrans GA, Kim YS, Hollmann MW, van Lieshout JJ. Cerebral hemodynamics during treatment with sodium nitroprusside versus labetalol in malignant hypertension. Hypertension 2008;52:236-40.  Back to cited text no. 39
Panacek EA, Bednarczyk EM, Dunbar LM, Foulke GE, Holcslaw TL. Randomized, prospective trial of fenoldopam vs sodium nitroprusside in the treatment of acute severe hypertension. Fenoldopam Study Group. Acad Emerg Med 1995;2:959-65.  Back to cited text no. 40
Neutel JM, Smith DH, Wallin D, Cook E, Ram CV, Fletcher E, et al. A comparison of intravenous nicardipine and sodium nitroprusside in the immediate treatment of severe hypertension. Am J Hypertens 1994;7:623-8.  Back to cited text no. 41
Yang HJ, Kim JG, Lim YS, Ryoo E, Hyun SY, Lee G. Nicardipine versus nitroprusside infusion as antihypertensive therapy in hypertensive emergencies. J Int Med Res 2004;32:118-23.  Back to cited text no. 42
Pluta RM, Oldfield EH, Boock RJ. Reversal and prevention of cerebral vasospasm by intracarotid infusions of nitric oxide donors in a primate model of subarachnoid hemorrhage. J Neurosurg 1997;87:746-51.  Back to cited text no. 43
Marshman LA, Morice AH, Thompson JS. Increased efficacy of sodium nitroprusside in middle cerebral arteries following acute subarachnoid hemorrhage: Indications for its use after rupture. J Neurosurg Anesthesiol 1998;10:171-7.  Back to cited text no. 44
Vajkoczy P, Hubner U, Horn P, Bauhuf C, Thome C, Schilling L, et al. Intrathecal sodium nitroprusside improves cerebral blood flow and oxygenation in refractory cerebral vasospasm and ischemia in humans. Stroke 2000;31:1195-7.  Back to cited text no. 45
Thomas JE, Rosenwasser RH. Reversal of severe cerebral vasospasm in three patients after aneurysmal subarachnoid hemorrhage: Initial observations regarding the use of intraventricular sodium nitroprusside in humans. Neurosurgery 1999;44:48-57.  Back to cited text no. 46
Joshi S, Duong H, Mangla S, Wang M, Libow AD, Popilskis SJ, et al. In nonhuman primates intracarotid adenosine, but not sodium nitroprusside, increases cerebral blood flow. Anesth Analg 2002;94:393-9.  Back to cited text no. 47
Joshi S, Young WL, Duong H, Aagaard BA, Ostapkovich ND, Connolly ES, et al. Intracarotid nitroprusside does not augment cerebral blood flow in human subjects. Anesthesiology 2002;96:60-6.  Back to cited text no. 48
Joshi S, Hartl R, Sun LS, Libow AD, Wang M, Pile-Spellman J, et al. Despite in vitro increase in cyclic guanosine monophosphate concentrations, intracarotid nitroprusside fails to augment cerebral blood flow of healthy baboons. Anesthesiology 2003;98:412-9.  Back to cited text no. 49
Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults:2007 update: A guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Circulation 2007;116:e391-413.  Back to cited text no. 50
Suri MF, Vazquez G, Ezzeddine MA, Qureshi AI. A multicenter comparison of outcomes associated with intravenous nitroprusside and nicardipine treatment among patients with intracerebral hemorrhage. Neurocrit Care 2009;11:50-5.  Back to cited text no. 51
Opasich C, Cioffi G, Gualco A. Nitroprusside in decompensated heart failure: What should a clinician really know? Curr Heart Fail Rep 2009;6:182-90.  Back to cited text no. 52
Heart Failure Society of America, Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010;16:e1-194.  Back to cited text no. 53
Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young JB, et al. Sodium nitroprusside for advanced low-output heart failure. J Am Coll Cardiol 2008;52:200-7.  Back to cited text no. 54
Capomolla S, Febo O, Opasich C, Guazzotti G, Caporotondi A, La Rovere MT, et al. Chronic infusion of dobutamine and nitroprusside in patients with end-stage heart failure awaiting heart transplantation: Safety and clinical outcome. Eur J Heart Fail 2001;3:601-10.  Back to cited text no. 55
Khot UN, Novaro GM, Popoviæ ZB, Mills RM, Thomas JD, Tuzcu EM, et al. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis. N Engl J Med 2003;348:1756-63.  Back to cited text no. 56
Elkayam U, Janmohamed M, Habib M, Hatamizadeh P. Vasodilators in the management of acute heart failure. Crit Care Med 2008;36:S95-105.  Back to cited text no. 57
Gelman S. The pathophysiology of aortic cross-clamping and unclamping. Anesthesiology 1995;82:1026-60.  Back to cited text no. 58
Jackson RS, Chang DC, Freischlag JA. Comparison of long-term survival after open vs endovascular repair of intact abdominal aortic aneurysm among Medicare beneficiaries. JAMA 2012;307:1621-8.  Back to cited text no. 59
Gloviczki P. Surgical repair of thoracoabdominal aneurysms: Patient selection, techniques and results. Cardiovasc Surg 2002;10:434-41.  Back to cited text no. 60
Ryan T, Mannion D, O'Brien W, Grace P, Bouchier-Hayes D, Cunningham AJ. Spinal cord perfusion pressure in dogs after control of proximal aortic hypertension during thoracic aortic cross-clamping with esmolol or sodium nitroprusside. Anesthesiology 1993;78:317-25.  Back to cited text no. 61
Simpson JI, Eide TR, Schiff GA, Clagnaz JF, Zisbrod Z, Newman SB, et al. Isoflurane versus sodium nitroprusside for the control of proximal hypertension during thoracic aortic cross-clamping: Effects on spinal cord ischemia. J Cardiothorac Vasc Anesth 1995;9:491-6.  Back to cited text no. 62
Simpson JI, Eide TR, Newman SB, Schiff GA, Levine D, Bermudez R, et al. Trimethaphan versus sodium nitroprusside for the control of proximal hypertension during thoracic aortic cross-clamping: The effects on spinal cord ischemia. Anesth Analg 1996;82:68-74.  Back to cited text no. 63
Marini CP, Grubbs PE, Toporoff B, Woloszyn TT, Coons MS, Acinapura AJ, et al. Effect of sodium nitroprusside on spinal cord perfusion and paraplegia during aortic cross-clamping. Ann Thorac Surg 1989;47:379-83.  Back to cited text no. 64
Aadahl P, Aakhus S, Strømholm T, Saether OD, Myhre HO. Effect of sodium nitroprusside on cardiac output during cross-clamping of the descending thoracic aorta in pigs. Eur Surg Res 1995;27:323-31.  Back to cited text no. 65
Oliver WC Jr, Nuttall GA, Cherry KJ, Decker PA, Bower T, Ereth MH. A comparison of fenoldopam with dopamine and sodium nitroprusside in patients undergoing cross-clamping of the abdominal aorta. Anesth Analg 2006;103:833-40.  Back to cited text no. 66
Dentz ME, Lubarsky DA, Smith LR, McCann RL, Moskop RJ, Inge W, et al. A comparison of amrinone with sodium nitroprusside for control of hemodynamics during infrarenal abdominal aortic surgery. J Cardiothorac Vasc Anesth 1995;9:486-90.  Back to cited text no. 67
Azakie A, Muse J, Gardner M, Skidmore KL, Miller SP, Karl TR, et al. Cerebral oxygen balance is impaired during repair of aortic coarctation in infants and children. J Thorac Cardiovasc Surg 2005;130:830-6.  Back to cited text no. 68
Moerman A, Bové T, François K, Jacobs S, Deblaere I, Wouters P, et al. Society of cardiovascular anesthesiologists: The effect of blood pressure regulation during aortic coarctation repair on brain, kidney, and muscle oxygen saturation measured by near-infrared spectroscopy: A randomized, clinical trial. Anesth Analg 2013;116:760-6.  Back to cited text no. 69
Tabbutt S, Nicolson SC, Dominguez TE, Wells W, Backer CL, Tweddell JS, et al. Perioperative course in 118 infants and children undergoing coarctation repair via a thoracotomy: A prospective, multicenter experience. J Thorac Cardiovasc Surg 2008;136:1229-36.  Back to cited text no. 70
Jaffe R, Charron T, Puley G, Dick A, Strauss BH. Microvascular obstruction and the no-reflow phenomenon after percutaneous coronary intervention. Circulation 2008;117:3152-6.  Back to cited text no. 71
Piana RN, Paik GY, Moscucci M, Cohen DJ, Gibson CM, Kugelmass AD, et al. Incidence and treatment of 'no-reflow' after percutaneous coronary intervention. Circulation 1994;89:2514-8.  Back to cited text no. 72
Pasceri V, Pristipino C, Pelliccia F, Granatelli A, Speciale G, Roncella A, et al. Effects of the nitric oxide donor nitroprusside on no-reflow phenomenon during coronary interventions for acute myocardial infarction. Am J Cardiol 2005;95:1358-61.  Back to cited text no. 73
Hallak JE, Maia-de-Oliveira JP, Abrao J, Evora PR, Zuardi AW, Crippa JA, et al. Rapid improvement of acute schizophrenia symptoms after intravenous sodium nitroprusside: A randomized, double-blind, placebo-controlled trial. JAMA Psychiatry 2013; 70:668-76.  Back to cited text no. 74
Yang L, Lan C, Fang Y, Zhang Y, Wang J, Guo J, et al. Sodium nitroprusside (SNP) sensitizes human gastric cancer cells to TRAIL-induced apoptosis. Int Immunopharmacol 2013;17:383-9.  Back to cited text no. 75
Arnold WP, Longnecker DE, Epstein RM. Photodegradation of sodium nitroprusside: Biologic activity and cyanide release. Anesthesiology 1984;61:254-60.  Back to cited text no. 76
Tinker JH, Michenfelder JD. Sodium nitroprusside: Pharmacology, toxicology and therapeutics. Anesthesiology 1976;45:340-54.  Back to cited text no. 77
Merrifield AJ, Blundell MD. Letter: Toxicity of sodium nitroprusside. Br J Anaesth 1974;46:324.  Back to cited text no. 78
Perschau RA, Modell JH, Bright RW, Shirley PD. Suspected sodium nitroprusside-induced cyanide intoxication. Anesth Analg 1977;56:533-7.  Back to cited text no. 79
Davies DW, Greiss L, Kadar D, Steward DJ. Sodium nitroprusside in children: Observations on metabolism during normal and abnormal responses. Can Anaesth Soc J 1975;22:553-60.  Back to cited text no. 80
Gobbel GT, Chan TY, Chan PH. Nitric oxide-and superoxide-mediated toxicity in cerebral endothelial cells. J Pharmacol Exp Ther 1997;282:1600-7.  Back to cited text no. 81
Niknahad H, O'Brien PJ. Involvement of nitric oxide in nitroprusside-induced hepatocyte cytotoxicity. Biochem Pharmacol 1996;51:1031-9.  Back to cited text no. 82
Kanthasamy AG, Ardelt B, Malave A, Mills EM, Powley TL, Borowitz JL, et al. Reactive oxygen species generated by cyanide mediate toxicity in rat pheochromocytoma cells. Toxicol Lett 1997;93:47-54.  Back to cited text no. 83
Alaniz C, Watts B. Monitoring cyanide toxicity in patients receiving nitroprusside therapy. Ann Pharmacother 2005;39:388-9.  Back to cited text no. 84
Baud FJ, Borron SW, Mégarbane B, Trout H, Lapostolle F, Vicaut E, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med 2002;30:2044-50.  Back to cited text no. 85
Cheung AT, Cruz-Shiavone GE, Meng QC, Pochettino A, Augoustides JA, Bavaria JE, et al. Cardiopulmonary bypass, hemolysis, and nitroprusside-induced cyanide production. Anesth Analg 2007;105:29-33.  Back to cited text no. 86
Harrison DG, Bates JN. The nitrovasodilators. New ideas about old drugs. Circulation 1993;87:1461-7.  Back to cited text no. 87
Cottrell JE, Patel K, Turndorf H, Ransohoff J. Intracranial pressure changes induced by sodium nitroprusside in patients with intracranial mass lesions. J Neurosurg 1978;48:329-31.  Back to cited text no. 88
Turner JM, Powell D, Gibson RM, McDowall DG. Intracranial pressure changes in neurosurgical patients during hypotension induced with sodium nitroprusside or trimetaphan. Br J Anaesth 1977;49:419-25.  Back to cited text no. 89
Weiss MH, Spence J, Apuzzo ML, Heiden JS, McComb JG, Kurze T. Influence of nitroprusside on cerebral pressure autoregulation. Neurosurgery 1979;4:56-9.  Back to cited text no. 90
Reade MC, Davies SR, Morley PT, Dennett J, Jacobs IC, Australian Resuscitation Council. Review article: Management of cyanide poisoning. Emerg Med Australas 2012;24:225-38.  Back to cited text no. 91
Nagasawa HT, Goon DJ, Crankshaw DL, Vince R, Patterson SE. Novel, orally effective cyanide antidotes. J Med Chem 2007;50:6462-4.  Back to cited text no. 92
Zerbe NF, Wagner BK. Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity. Crit Care Med 1993;21:465-7.  Back to cited text no. 93
Crankshaw DL, Goon DJ, Briggs JE, DeLong D, Kuskowski M, Patterson SE, et al. A novel paradigm for assessing efficacies of potential antidotes against neurotoxins in mice. Toxicol Lett 2007;175:111-7.  Back to cited text no. 94
Brenner M, Kim JG, Lee J, Mahon SB, Lemor D, Ahdout R, et al. Sulfanegen sodium treatment in a rabbit model of sub-lethal cyanide toxicity. Toxicol Appl Pharmacol 2010;248:269-76.  Back to cited text no. 95
Belani KG, Singh H, Beebe DS, George P, Patterson SE, Nagasawa HT, et al. Cyanide toxicity in juvenile pigs and its reversal by a new prodrug, sulfanegen sodium. Anesth Analg 2012;114:956-61.  Back to cited text no. 96


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2]

This article has been cited by
1 Modulating the Bioactivity of Nitric Oxide as a Therapeutic Strategy in Cardiac Surgery
Oleg Pisarenko,Irina Studneva
Journal of Surgical Research. 2021; 257: 178
[Pubmed] | [DOI]
2 Complex Metal Ions: Neuropsychiatric and Imaging Features
James R. Bateman,Katherine H. Taber,Robin A. Hurley
The Journal of Neuropsychiatry and Clinical Neurosciences. 2020; 32(4): A4
[Pubmed] | [DOI]
3 Approach to the Patient: Perioperative Management of the Patient with Pheochromocytoma or Sympathetic Paraganglioma
Annika M A Berends,Michiel N Kerstens,Jacques W M Lenders,Henri J L M Timmers
The Journal of Clinical Endocrinology & Metabolism. 2020; 105(9)
[Pubmed] | [DOI]
4 Novel cyclometalated Ru(II) complexes containing isoquinoline ligands: Synthesis, characterization, cellular uptake and in vitro cytotoxicity
Jincan Chen,Jie Wang,Yuanyuan Deng,Baojun Li,Chengpeng Li,Yuxue Lin,Dongbin Yang,Huanyun Zhang,Lanmei Chen,Tao Wang
European Journal of Medicinal Chemistry. 2020; : 112562
[Pubmed] | [DOI]
5 Crystal structure and infrared and Raman spectra of K3[Cr(CN)5NO].2H2O, a member of an iconic family of complexes in coordination chemistry
Oscar E. Piro,Gustavo A. Echeverría,Alda Navaza,Jorge A. Güida
Inorganica Chimica Acta. 2020; 511: 119831
[Pubmed] | [DOI]
6 The solution chemistry of nitric oxide and other reactive nitrogen species
Peter C. Ford,Katrina M. Miranda
Nitric Oxide. 2020; 103: 31
[Pubmed] | [DOI]
7 Pharmacologic Control of Blood Pressure in Infants and Children
Joseph D. Tobias,Aymen Naguib,Janet Simsic,Catherine D. Krawczeski
Pediatric Cardiology. 2020;
[Pubmed] | [DOI]
8 Clevidipine as a therapeutic and cost-effective alternative to sodium nitroprusside in patients with acute aortic syndromes
Carlos L Alviar,Alejandra Gutierrez,Leslie Cho,Amar Krishnaswamy,Amr Saleh,Michael A Lincoff,Eric Roselli,Michael Militello,Venu Menon
European Heart Journal: Acute Cardiovascular Care. 2020; 9(3_suppl): S5
[Pubmed] | [DOI]
9 Evaluation of intramuscular sodium nitroprusside injection to improve oxygenation in medetomidine–alfaxalone–azaperone anesthetized white-tailed deer (Odocoileus virginianus)
Sarifa Lakhdhir,Nigel A. Caulkett,Tanya Duke-Novakovski,Murray Woodbury,Søren Boysen
Veterinary Anaesthesia and Analgesia. 2020;
[Pubmed] | [DOI]
10 The effect of hyperglycemia on neurovascular coupling and cerebrovascular patterning in zebrafish
Karishma Chhabria,Karen Plant,Oliver Bandmann,Robert N Wilkinson,Chris Martin,Elisabeth Kugler,Paul A Armitage,Paola LM Santoscoy,Vincent T Cunliffe,Jan Huisken,Alexander McGown,Tennore Ramesh,Tim JA Chico,Clare Howarth
Journal of Cerebral Blood Flow & Metabolism. 2020; 40(2): 298
[Pubmed] | [DOI]
11 A divergent mode of activation of a nitrosyl iron complex with unusual antiangiogenic activity
Edinilton Muniz Carvalho,Lisa A. Ridnour,Florêncio Sousa Gouveia Júnior,Pedro Henrique Bezerra Cabral,Nilberto Robson Falcão do Nascimento,David A. Wink,Douglas W. Franco,Mayara Jane Campos de Medeiros,Daniel de Lima Pontes,Elisane Longhinotti,Tércio de Freitas Paulo,Vania Bernardes-Génisson,Remi Chauvin,Eduardo Henrique Silva Sousa,Luiz Gonzaga de França Lopes
Journal of Inorganic Biochemistry. 2020; : 111133
[Pubmed] | [DOI]
12 Donors of nitric oxide and their application for increase in plants resistance to action of abiotic stressors
Yu. V. Karpets
Vìsnik Harkìvs'kogo nacìonal'nogo agrarnogo unìversitetu. Serìâ Bìologiâ. 2019; 2019(3): 28
[Pubmed] | [DOI]
13 An electrochemical investigation into the effects of local and systemic administrations of sodium nitroprusside in brain extracellular fluid of mice
Caroline H. Reid,Niall J. Finnerty
Bioelectrochemistry. 2019; : 107441
[Pubmed] | [DOI]
14 Controlled Delivery of Nitric Oxide for Cancer Therapy
Houman Alimoradi,Khaled Greish,Allan B. Gamble,Gregory I. Giles
Pharmaceutical Nanotechnology. 2019; 7(4): 279
[Pubmed] | [DOI]
15 Ameliorative effect of Parinari curatellifolia seed extracts on sodium nitroprusside–induced cardiovascular toxicity in rats
Sunday S. Josiah,Sunday I. Oyeleye,Olamide O. Crown,Mary T. Olaleye
Comparative Clinical Pathology. 2019;
[Pubmed] | [DOI]
16 Acute Management of Hypertension Following Intracerebral Hemorrhage
J. Tyler Haller,Adam L. Wiss,Casey C. May,G. Morgan Jones,Keaton S. Smetana
Critical Care Nursing Quarterly. 2019; 42(2): 129
[Pubmed] | [DOI]
17 NO donors induce vascular relaxation by different cellular mechanisms in hypertensive and normotensive rats
Alice V. Araújo,Fernanda A. Andrade,Michele Paulo,Tiago D. de Paula,Simone R. Potje,Amanda C. Pereira,Lusiane M. Bendhack
Nitric Oxide. 2019; 86: 12
[Pubmed] | [DOI]
18 Efficacy and Tolerability of Adjunctive Intravenous Sodium Nitroprusside Treatment for Outpatients With Schizophrenia
Hannah E. Brown,Oliver Freudenreich,Xiaoduo Fan,Stephen O. Heard,Donald Goff,George Petrides,Amy L. Harrington,John M. Kane,Heidi Judge,Bettina Hoeppner,Maurizio Fava,Roy H. Perlis
JAMA Psychiatry. 2019;
[Pubmed] | [DOI]
19 Management of Blood Pressure During and After Recanalization Therapy for Acute Ischemic Stroke
Jeffrey R. Vitt,Michael Trillanes,J. Claude Hemphill
Frontiers in Neurology. 2019; 10
[Pubmed] | [DOI]
20 Incorporation of Nitroprusside on Silica Nanoparticles—A Strategy for Safer Use of This NO Donor in Therapy
Pedro M. Silva Filho,Iury A. Paz,Nilberto R. F. Nascimento,Cláudia F. Santos,Valdevane R. Araújo,Camila P. Aquino,T. S. Ribeiro,Igor F. Vasconcelos,Luiz G. F. Lopes,Eduardo H. S. Sousa,Elisane Longhinotti
Molecular Pharmaceutics. 2019;
[Pubmed] | [DOI]
21 Dissociation between macro- and microvascular parameters in the early phase of hemorrhagic shock
Ronald Lima,Nivaldo Villela,Raquel Castiglione,Maria das Graças C. de Souza,Eliete Bouskela
Microvascular Research. 2019; : 103909
[Pubmed] | [DOI]
22 Biodegradable Therapeutic Microneedle Patch for Rapidly Antihypertensive Treatment
Yan Li,Fanmao Liu,Chen Su,Bingbo Yu,Di Liu,Hui-Jiuan Chen,Di-an Lin,Chengduan Yang,Lingfei Zhou,Qianni Wu,Wenhao Xia,Xi Xie,Jun Tao
ACS Applied Materials & Interfaces. 2019;
[Pubmed] | [DOI]
23 A Review of Middle Aortic Syndromes in Pediatric Patients
Nell Forman,Jina Sinskey,Ahmed Shalabi
Journal of Cardiothoracic and Vascular Anesthesia. 2019;
[Pubmed] | [DOI]
24 Electronic structure, topological analysis and spectroscopic properties of sandwich indenyl complexes of ruthenium: A theoretical study
Souhila Laib,Wahiba Boussebbat
Journal of Molecular Structure. 2019; 1189: 219
[Pubmed] | [DOI]
25 Demystifying Lactate in the Emergency Department
Gabriel Wardi,Jessica Brice,Matthew Correia,Dennis Liu,Michael Self,Christopher Tainter
Annals of Emergency Medicine. 2019;
[Pubmed] | [DOI]
26 Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis
Xiaowei Niu,Jingjing Zhang,Ming Bai,Yu Peng,Shaobo Sun,Zheng Zhang
BMC Cardiovascular Disorders. 2018; 18(1)
[Pubmed] | [DOI]
27 Sodium Nitroprusside as a Hyperinflation Drug and Therapeutic Alternatives
Alex Cobb,Luciana Thornton
Journal of Pharmacy Practice. 2018; 31(4): 374
[Pubmed] | [DOI]
28 Nitric Oxide Release from Antimicrobial Peptide Hydrogels for Wound Healing
Joana Durão,Nuno Vale,Salomé Gomes,Paula Gomes,Cristina C. Barrias,Luís Gales
Biomolecules. 2018; 9(1): 4
[Pubmed] | [DOI]
29 In Vitro Effects of Sodium Nitroprusside and L-N?-Nitroarginine Methyl Ester (L-NAME) on Activity of Lysosomal Cysteine Proteinases and Lysosomal Membrane Permeability
M. A. Fomina,A. M. Kudlaeva,S. A. Isakov,V. V. Davydov
Bulletin of Experimental Biology and Medicine. 2018;
[Pubmed] | [DOI]
30 Hyperinflation of Nitroprusside
Alex Cobb,Luciana Thornton
Journal of Pharmacy Practice. 2018; 31(4): 382
[Pubmed] | [DOI]
31 New NMR investigation of [RuF 5 NO] 2- anion
L. Diana Castañeda Trujillo,Jorge L. Jios,Carlos A. Franca,Jorge A. Güida
Inorganica Chimica Acta. 2018; 477: 130
[Pubmed] | [DOI]
32 Clinical use of plasma lactate concentration. Part 1: Physiology, pathophysiology, and measurement
Patricia G. Rosenstein,Brett S. Tennent-Brown,Dez Hughes
Journal of Veterinary Emergency and Critical Care. 2018; 28(2): 85
[Pubmed] | [DOI]
33 Endothelial modulation of a nitric oxide donor complex-induced relaxation in normotensive and spontaneously hypertensive rats
Simone R. Potje,Jéssica A. Troiano,Marcella D. Grando,Murilo E. Graton,Roberto S. da Silva,Lusiane M. Bendhack,Cristina Antoniali
Life Sciences. 2018;
[Pubmed] | [DOI]
34 Brugada-type electrocardiogram changes associated with nitroprusside toxicity
Jonathan T. Jaffe,Lee-Gardie Jean,Richard J. Murray
HeartRhythm Case Reports. 2018; 4(3): 89
[Pubmed] | [DOI]
35 Thiocarbonyl-bound metallonitrosyl complexes with visible-light induced DNA cleavage and promising vasodilation activity
Carlos D.S. Silva,Iury A. Paz,Felipe D. Abreu,Aurideia P. de Sousa,Carla P. Veríssimo,Nilberto R.F. Nascimento,Tércio F. Paulo,Davila Zampieri,Marcos N. Eberlin,Ana C.S. Gondim,Loraine C. Andrade,Idalina M.M. Carvalho,Eduardo H.S. Sousa,Luiz G.F. Lopes
Journal of Inorganic Biochemistry. 2018; 182: 83
[Pubmed] | [DOI]
36 Local Delivery and Sustained-Release of Nitric Oxide Donor Loaded in Mesoporous Silica Particles for Efficient Treatment of Primary Open-Angle Glaucoma
Chunchun Hu,Jianguo Sun,Yu Zhang,Jian Chen,Yuan Lei,Xinghuai Sun,Yonghui Deng
Advanced Healthcare Materials. 2018; : 1801047
[Pubmed] | [DOI]
37 Bridging Structural and Dynamical Models of a Confined Sodium Nitroprusside Complex
Fabien Deligey,Sabine Bouguet-Bonnet,Abdelatif Doudouh,Pierre-Louis Marande,Dominik Schaniel,Axel Gansmüller
The Journal of Physical Chemistry C. 2018; 122(38): 21883
[Pubmed] | [DOI]
38 Low Concentration of Sodium Nitroprusside Promotes Mesenchymal Stem Cell Viability and Proliferation Through Elevation of Metabolic Activity
Atefeh Mohammadi,Mohammad Hussein Abnosi,Reza Pakyari
Avicenna Journal of Medical Biochemistry. 2017; 5(1): 9
[Pubmed] | [DOI]
39 Recent Development of Hydrogen Sulfide Releasing/Stimulating Reagents and Their Potential Applications in Cancer and Glycometabolic Disorders
Chun-tao Yang,Li Chen,Shi Xu,Jacob J. Day,Xiang Li,Ming Xian
Frontiers in Pharmacology. 2017; 8
[Pubmed] | [DOI]
40 Drug-induced hyperlactatemia
Eike Blohm,Jeffrey Lai,Mark Neavyn
Clinical Toxicology. 2017; : 1
[Pubmed] | [DOI]
41 Epigenetics: The third pillar of nitric oxide signaling
Samantha Socco,Rhea C. Bovee,Marianne B. Palczewski,Jason R. Hickok,Douglas D. Thomas
Pharmacological Research. 2017; 121: 52
[Pubmed] | [DOI]
42 Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells
Oksana Mayevska,Oleh Chen,Olena Karatsai,Yaroslav Bobak,Maryna Barska,Liliana Lyniv,Iuliia Pavlyk,Yuriy Rzhepetskyy,Natalia Igumentseva,Maria Jolanta Redowicz,Oleh Stasyk
Experimental Cell Research. 2017;
[Pubmed] | [DOI]
43 Advances in the design of organometallic anticancer complexes
Pingyu Zhang,Peter J. Sadler
Journal of Organometallic Chemistry. 2017; 839: 5
[Pubmed] | [DOI]
44 Treatment with sodium nitroprusside improves the endothelial function in aortic rings with endothelial dysfunction
Tereza Cristina Buzinari,Jorge Camargo Oishi,Thiago Francisco De Moraes,Izabela Pereira Vatanabe,Cezar Rangel Pestana,Gerson Jhonatan Rodrigues
European Journal of Pharmaceutical Sciences. 2017;
[Pubmed] | [DOI]
45 Efficacy and safety of intracoronary verapamil versus sodium nitroprusside for the prevention of microvascular obstruction during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction
Hesham K. Abdelaziz,Wael Elkilany,Said Khalid,Sameh Sabet,Marwan Saad
Coronary Artery Disease. 2017; 28(1): 11
[Pubmed] | [DOI]
46 NO and HNO donors, nitrones, and nitroxides: Past, present, and future
Catarina Oliveira,Sofia Benfeito,Carlos Fernandes,Fernando Cagide,Tiago Silva,Fernanda Borges
Medicinal Research Reviews. 2017;
[Pubmed] | [DOI]
47 The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics
Sanjay Divakaran,Joseph Loscalzo
Journal of the American College of Cardiology. 2017; 70(19): 2393
[Pubmed] | [DOI]
48 Jujuboside B Reduces Vascular Tension by Increasing Ca2+ Influx and Activating Endothelial Nitric Oxide Synthase
Yixiu Zhao,Xin Zhang,Jiannan Li,Yu Bian,Miaomiao Sheng,Bin Liu,Zidong Fu,Yan Zhang,Baofeng Yang,John Calvert
PLOS ONE. 2016; 11(2): e0149386
[Pubmed] | [DOI]
49 MK-801-induced impairments on the trial-unique, delayed nonmatching-to-location task in rats: effects of acute sodium nitroprusside
Jessica L. Hurtubise,Wendie N. Marks,Don A. Davies,Jillian K. Catton,Glen B. Baker,John G. Howland
Psychopharmacology. 2016;
[Pubmed] | [DOI]
50 Managing vasoactive infusions to restore hemodynamic stability
Rosemary A. Timmerman
Nursing Critical Care. 2016; 11(2): 35
[Pubmed] | [DOI]
51 Therapies to Reduce Blood Pressure Acutely
Joseph B. Miller,Harish Kinni,Ahmed Amer,Phillip D. Levy
Current Hypertension Reports. 2016; 18(6)
[Pubmed] | [DOI]
52 The cyclic GMP/protein kinase G pathway as a therapeutic target in head and neck squamous cell carcinoma
Traci R. Tuttle,Michelle L. Mierzwa,Susanne I. Wells,Sejal R. Fox,Nira Ben-Jonathan
Cancer Letters. 2016; 370(2): 279
[Pubmed] | [DOI]
53 Sodium nitroprusside has leishmanicidal activity independent of iNOS
Natália Yoshie Kawakami,Fernanda Tomiotto-Pellissier,Allan Henrique Depieri Cataneo,Tatiane Marcusso Orsini,Ana Paula Fortes Dos Santos Thomazelli,Carolina Panis,Ivete Conchon-Costa,Wander Rogério Pavanelli
Revista da Sociedade Brasileira de Medicina Tropical. 2016; 49(1): 68
[Pubmed] | [DOI]
54 Ammonium tetrathiomolybdate as a water-soluble and slow-release hydrogen sulfide donor
Shi Xu,Chun-Tao Yang,Fu-Hui Meng,Armando Pacheco,Li Chen,Ming Xian
Bioorganic & Medicinal Chemistry Letters. 2016;
[Pubmed] | [DOI]
55 Drugs modulating the L-arginine:NO:cGMP pathway – current use in therapy
Magdalena Polakowska,Jolanta Orzelska-Gorka,Sylwia Talarek
Current Issues in Pharmacy and Medical Sciences. 2016; 29(1)
[Pubmed] | [DOI]
56 Exercise training attenuates the pressor response evoked by peripheral chemoreflex in rats with heart failure
Leonardo Calegari,Bruna B. Mozzaquattro,Douglas D. Rossato,Edson Quagliotto,Janaina B. Ferreira,Alberto Rasia-Filho,Pedro Dal Lago
Canadian Journal of Physiology and Pharmacology. 2016; : 1
[Pubmed] | [DOI]
57 Overview and New Insights into the Thiol Reactivity of Coordinated NO in {MNO}6/7/8(M = Fe, Co) Complexes
Melody A. Rhine,Brian C. Sanders,Ashis K. Patra,Todd C. Harrop
Inorganic Chemistry. 2015; 54(19): 9351
[Pubmed] | [DOI]
58 Novel Treatments of Psychosis
Walter Dunn,Stephen R. Marder
Current Behavioral Neuroscience Reports. 2015;
[Pubmed] | [DOI]
59 Alpha-ketoglutarate attenuates toxic effects of sodium nitroprusside and hydrogen peroxide in Drosophila melanogaster
Maria M. Bayliak,Halyna V. Shmihel,Maria P. Lylyk,Oksana M. Vytvytska,Janet M. Storey,Kenneth B. Storey,Volodymyr I. Lushchak
Environmental Toxicology and Pharmacology. 2015; 40(2): 650
[Pubmed] | [DOI]
60 Whole finger iontophoresis of sodium nitroprusside to increase blood flow in patients with systemic sclerosis: Influence of concentration
Jayne Little,Andrea Murray,Graham Dinsdale,Jack Wilkinson,Tonia Moore,Ariane L. Herrick
International Journal of Pharmaceutics. 2015; 490(1-2): 446
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
   Introduction and...
   Mechanism of Act...
   Clinical Use, Ef...
   Metabolism, Safe...
   Antidotes: Mecha...
   Article Figures
   Article Tables

 Article Access Statistics
    PDF Downloaded2123    
    Comments [Add]    
    Cited by others 60    

Recommend this journal