Version May 2024
Acute respiratory distress syndrome, moderate to severe, refractory (off-label use): Note: Routine use is not recommended due to lack of impact on clinical outcomes (mortality, length of stay, mechanical ventilation duration) and a possible increased risk of kidney injury. However, may be used as rescue therapy to improve oxygenation if nonpharmacologic measures are ineffective. Based on limited data; optimal dosing strategy and titration remains unknown; refer to institutional policies and procedures (Adhikari 2014; Dzierba 2014; Gebistorf 2016; Griffiths 2019; Ruan 2015).
Inhalation: Initial dose: 5 to 10 parts per million (ppm); titrate to lowest effective dose based on clinical response and tolerability; usual dosage range: 1.25 to 40 ppm (Adhikari 2014; Dzierba 2014; Taylor 2004).
Acute vasodilator testing in patients with pulmonary arterial hypertension (off-label use):
Note: Acute vasodilator testing is recommended in patients with idiopathic, heritable, or drug-induced pulmonary arterial hypertension to assess eligibility for treatment with a calcium channel blocker (eg, ER nifedipine) (ACCF/AHA [McLaughlin 2009]; ESC/ERS [Humbert 2022]).
Inhalation: Usual dosage range: 10 to 80 ppm for 5 to 10 minutes while measuring hemodynamic response; may discontinue without weaning (ACC/AHA [McLaughlin 2009]; ESC/ERS [Humbert 2022]).
Right ventricular dysfunction after cardiac surgery (off-label use): Inhalation: Usual dose: 20 ppm via mechanical ventilation circuit; dosage range: 5 to 20 ppm (Argenziano 1998; Costanzo 2010; Mosquera 2002; Paniagua 1999).
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Cardiovascular: Hypotension (14%)
Frequency not defined:
Cardiovascular: Increased pulmonary artery pressure (with abrupt discontinuation)
Hematologic & oncologic: Methemoglobinemia
Respiratory: Hypoxemia (with abrupt discontinuation)
Neonates dependent on right-to-left shunting of blood
Concerns related to adverse effects:
• Airway injury: May result from inflammation and lung tissue damage caused by nitrogen dioxide (NO2) formed in nitric oxide and oxygen gas mixtures. If there is an unexpected change in NO2 concentration, or if NO2 concentration in the breathing circuit reaches the manufacturer-recommended maximum ppm, assess delivery system and recalibrate the NO2 analyzer; adjust dose of nitric oxide and/or FiO2 as appropriate.
• Methemoglobinemia: Dose-related methemoglobin (when nitric oxide combines with hemoglobin) may occur and lead to hypoxemia; monitor methemoglobin concentrations within 4 to 8 hours of starting nitric oxide treatment and then periodically; optimize oxygenation by adjusting nitric oxide dose as necessary. If methemoglobin levels do not resolve with decrease in dose or discontinuation of nitric oxide, additional therapy may be warranted.
• Platelet dysfunction: Inhaled nitric oxide may decrease platelet aggregation and agglutination without any impact on bleeding times. Although clinical trials have not observed any significant increases in bleeding rates associated with inhaled nitric oxide, patients with bleeding risk factors should be monitored closely (Dzierba 2014).
• Renal dysfunction: Inhaled nitric oxide may increase the risk of kidney injury. Although the exact mechanism remains unknown, inhaled nitric oxide may negatively impair the function of mitochondria and deoxyribonucleic acid as well as other various enzymes leading to renal failure (Gebistorf 2016; Ruan 2015).
Disease-related concerns:
• Heart failure: Use in patients with left ventricular dysfunction may increase pulmonary capillary wedge pressure, worsen left ventricular dysfunction, and cause pulmonary edema, systemic hypotension, bradycardia, and cardiac arrest; discontinue nitric oxide and provide symptomatic care.
• Pulmonary artery hypertension: Acute vasodilator testing (not an approved use): Use with extreme caution in patients with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis; significant decompensation has occurred resulting in acute pulmonary edema.
Other warnings/precautions:
• Abrupt discontinuation: Avoid abrupt discontinuation; may lead to worsening oxygenation, and increasing pulmonary artery pressure (PAP) (ie, rebound pulmonary hypertension syndrome). Signs and symptoms of rebound pulmonary hypertension syndrome include hypoxemia, systemic hypotension, bradycardia, and reduced cardiac output; reinitiate nitric oxide immediately if this occurs. In order to wean, titrate down in many steps (pause several hours at each step) and monitor for hypoxemia.
• Appropriate use: Doses above 20 ppm should not be used (or should be used with caution [off-label dosing]) because of the increased risk of methemoglobinemia and elevated levels of NO2, a toxic metabolite. Methemoglobin concentrations and inspired NO2 should be monitored.
• Lack of response: Worsening oxygenation and increasing PAP may occur in patients who do not respond.
Elevations in methemoglobin and nitrogen dioxide may be signs of overdose. Elevated nitrogen dioxide may cause acute lung injury and elevations of methemoglobin reduce the oxygen delivery capacity of the circulation. NO2 levels >3 ppm or methemoglobin levels >7% were treated by reducing the dose of or discontinuing nitric oxide. Methemoglobinemia that does not resolve with dosage reduction or discontinuation of therapy may require intravenous vitamin C, intravenous methylene blue, or blood transfusion, depending on the clinical situation.
Use in premature neonates (GA ≤34 weeks) is not recommended based on data from trials and meta-analysis. Nitric oxide (rescue and routine use for respiratory failure) did not improve survival nor was it found effective in the prevention or amelioration of bronchopulmonary dysplasia (AAP [Kumar 2014]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gas, Inhalation:
Genosyl Delivery System: Cassettes produce ≥216 liters of 800 ppm nitric oxide gas (at standard temperature and pressure)
Inomax: 0.08% (1 ea)
Noxivent: 0.01% (1 ea); 0.08% (1 ea)
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Gas, Inhalation:
Kinox: 0.01% (1 ea); 0.08% (1 ea)
Noxivent: 0.08% (1 ea)
Inhalation: Administration of nitric oxide should be done by a health care professional who has completed a comprehensive training program, and may only be administered using a calibrated delivery system with validated ventilator systems. To prevent treatment interruptions (power and system failures), immediate access to a backup battery power supply and an independent reserve nitric oxide delivery system is essential. Do not abruptly discontinue; must wean. To wean nitric oxide, titrate down in several steps, pausing several hours before reducing further; monitor for hypoxemia.
Inhalation: Administration of nitric oxide should be done by a health care professional who has completed a comprehensive periodic training program. May only be administered using a calibrated delivery system with validated ventilator systems. To prevent treatment interruptions due to power and/or system failures, immediate access to a backup battery power supply and an independent reserve nitric oxide delivery system is essential. Do not abruptly discontinue; must wean. To wean nitric oxide, titrate down in several steps, pausing several hours before reducing further; monitor for hypoxemia.
Hypoxic respiratory failure associated with pulmonary hypertension in neonates: Treatment of term and near-term (>34 weeks gestational age) neonates with hypoxic respiratory failure associated with clinical or echocardiographic evidence of pulmonary hypertension to improve oxygenation and reduce the need for extracorporeal membrane oxygenation. Used in conjunction with ventilatory support and other agents.
Acute respiratory distress syndrome, refractory moderate to severe; Acute vasodilator testing in patients with pulmonary arterial hypertension; Right ventricular dysfunction after cardiac surgery
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Methemoglobinemia Associated Agents: Nitric Oxide may enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy
Although the risk of adverse outcomes is increased in pregnant patients with pulmonary arterial hypertension (PAH), data specific to the diagnostic or therapeutic use of nitric oxide in pregnancy are limited. Use of inhaled nitric oxide for acute vasodilator testing has been described in a pregnant patient with PAH (Mojoli 2006). Inhaled nitric oxide may be used to improve pulmonary blood flow and oxygenation in pregnant patients with PAH who also have cardiac decompensation (AHA [Canobbio 2017]; Ballard 2021; Hemnes 2015).
Use of inhaled nitric oxide has been described for the treatment of severe COVID-19 pneumonia during pregnancy, and severe acute respiratory distress syndrome (ARDS) in pregnant or postpartum patients with or without COVID-19 (Garcha 2020; Mehrotra 2017; Palmrich 2021; Paramanathan 2021; Safaee Fakhr 2020; Valsecchi 2022); however, use of inhaled nitric oxide is not recommended for the routine treatment of severe ARDS in patients with COVID-19; nitric oxide may be considered as rescue therapy when other options have failed (NIH 2022).
Nitric oxide and metabolites are endogenous to breast milk (Akçay 2020; Hord 2011).
Respiratory status including arterial blood gases with close attention to PaO2, methemoglobin (measured within 4 to 8 hours after initiation and periodically throughout treatment), inspired NO2, vital signs.
In neonates with persistent pulmonary hypertension, nitric oxide improves oxygenation. Nitric oxide relaxes vascular smooth muscle by binding to the heme moiety of cytosolic guanylate cyclase, activating guanylate cyclase and increasing intracellular levels of cyclic guanosine 3',5'-monophosphate, which leads to vasodilation. When inhaled, pulmonary vasodilation occurs and an increase in the partial pressure of arterial oxygen results. Dilation of pulmonary vessels in well ventilated lung areas redistributes blood flow away from lung areas where ventilation/perfusion ratios are poor.
Absorption: Systemic after inhalation
Metabolism: Nitric oxide combines with hemoglobin that is 60% to 100% oxygenated. Nitric oxide combines with oxyhemoglobin to produce methemoglobin and nitrate. Within the pulmonary system, nitric oxide can combine with oxygen and water to produce nitrogen dioxide and nitrite respectively, which interact with oxyhemoglobin to then produce methemoglobin and nitrate. At 80 ppm the methemoglobin percent is ~5% in neonates after 8 hours of administration; methemoglobin levels >7% were attained only in neonates receiving 80 ppm. Doses >20 ppm are not recommended for use in neonatal patients.
Excretion: Urine
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
