نمای کلی
- ماده موثره
- نیتروگلیسیرین
- طبقه‌بندی دارویی
- وازودیلاتور نیترات
- اثر فیزیولوژیک
- اتساع عروق
- ساختار شیمیایی
- نیترات ها
- راه مصرف
- داخل وریدی
- تاریخ برچسب
- 2022-12-09
موارد مصرف
نیتروگلیسیرین در تزریق دکستروز 5% برای درمان فشار خون بالا حین عمل اندیکاسیون دارد. برای کنترل نارسایی قلبی در شرایط انفارکتوس حاد میوکارد؛ برای درمان آنژین صدری در بیمارانی که به نیتروگلیسیرین زیرزبانی و بلوکرهای β پاسخ نداده اند. و برای القای افت فشار خون حین عمل.
دوز و روش مصرف
نیتروگلیسیرین در تزریق دکستروز 5 درصد برای تزریق داخل وریدی با استفاده از تجهیزات استریل در نظر گرفته شده است. نیتروگلیسیرین را در تزریق دکستروز 5% فقط از طریق یک پمپ انفوزیون که می تواند سرعت تزریق را ثابت نگه دارد، تجویز کنید. از ظرفی که خلاء خود را از دست داده است و یا از ظرفی که ذرات معلق در آن قابل مشاهده است استفاده نکنید. دوز بستگی به نوع مجموعه انفوزیون مورد استفاده دارد (به هشدارها مراجعه کنید). اگرچه دوز معمول شروع بزرگسالان در مطالعات منتشر شده 25 میکروگرم در دقیقه یا بیشتر بوده است، این مطالعات از لوله PVC استفاده کردند، بنابراین دوزهای تحویلی کمتر از دوزهای گزارش شده بود. هنگامی که از لوله های غیرجذب استفاده می شود، دوزها باید کاهش یابد (به هشدارها و اقدامات احتیاطی مراجعه کنید). دوز باید بر اساس نیاز فردی بیمار و بسته به پاسخ مورد نیاز و عوارض جانبی احتمالی تعیین شود (به واکنش های نامطلوب مراجعه کنید). حتی با استفاده از لوله های غیرجذب، دوز لازم برای دستیابی به یک پاسخ معین از بیمار به بیمار دیگر بسیار متفاوت است. بیماران با فشار پر شدن بطن چپ نرمال یا پایین (مثلاً بیماران مبتلا به آنژین صدری بدون عارضه) ممکن است به کمتر از 5 میکروگرم در دقیقه پاسخ کامل دهند، در حالی که سایر بیماران ممکن است به دوزی که یک یا حتی دو مرتبه بزرگتر است نیاز داشته باشند. پایش مداوم فشار خون و ضربان قلب در تمام بیمارانی که این دارو را دریافت می کنند ضروری است. در بسیاری از موارد، نظارت تهاجمی بر فشار گوه مویرگی ریوی نیز نشان داده خواهد شد. غلظت‌های پایین‌تر نیتروگلیسیرین در تزریق دکستروز 5 درصد، دقت بالقوه دوز را افزایش می‌دهد، اما این غلظت‌ها حجم کلی مایعی را که باید به بیمار تحویل داده شود، افزایش می‌دهد. بار کلی مایع ممکن است در بیمارانی که عملکرد قلب، کبد و/یا کلیه‌ها به خطر افتاده است، مورد توجه قرار گیرد. دبی های لازم برای دستیابی به دزهای مختلف با غلظت های موجود در جدول زیر نشان داده شده است. با استفاده از لوله غیرجذب، دوز اولیه نیتروگلیسیرین بزرگسالان در تزریق دکستروز 5% باید mcg/min 5 باشد. تیتراسیون بعدی باید بر اساس نتایج بالینی هدایت شود و با مشاهده پاسخ نسبی، افزایش دوز محتاط تر می شود. تیتراسیون اولیه باید با افزایش mcg/min 5 در فواصل 3 تا 5 دقیقه باشد. اگر هیچ پاسخی در mcg/min 20 مشاهده نشد، می توان از افزایش 10 و حتی 20 میکروگرم در دقیقه استفاده کرد. هنگامی که برخی از پاسخ های همودینامیک مشاهده شد، افزایش دوز باید کوچکتر و کمتر باشد. هنگامی که غلظت تغییر می کند، لوله باید از بیمار جدا شود و قبل از ادامه درمان با محلول جدید شسته شود. اگر این احتیاط انجام نشود، بسته به لوله، پمپ و سرعت جریان مورد استفاده، ممکن است چند ساعت طول بکشد تا نیتروگلیسیرین با سرعت مورد نظر تحویل داده شود. محصولات دارویی تزریقی باید قبل از تجویز، هر زمان که محلول و ظرف اجازه می دهد، از نظر وجود ذرات معلق و تغییر رنگ به صورت چشمی بازرسی شوند. مصرف نکنید مگر اینکه محلول شفاف و مهر و موم آن سالم باشد. از افزودن داروی مکمل به نیتروگلیسیرین در تزریق دکستروز 5 درصد خودداری کنید. سرعت انفوزیون (mL/h) = [دوز (mcg/min) x 60 min/h] غلظت (mcg/mL) محاسبات مثالی برای نرخ انفوزیون به شرح زیر است: مثال 1: برای دوز 30 میکروگرم در دقیقه با استفاده از غلظت mcg/mL 100، سرعت انفوزیون به صورت زیر است: سرعت انفوزیون (mL/h) = [30 (mcg/min) x 60 (min/h)] = 18 (mL/h) 100 (mcg/mL) مثال 2: برای دوز 240 میکروگرم در دقیقه با استفاده از غلظت mcg/mL 400، سرعت انفوزیون به صورت زیر خواهد بود. (mcg/min) x 60 (min/h)] = 36 (mL/h) 400 (mcg/mL)
موارد منع مصرف
نیتروگلیسیرین در تزریق دکستروز 5 درصد در بیمارانی که به آن حساسیت دارند منع مصرف دارد. در بیماران مبتلا به تامپوناد پریکارد، کاردیومیوپاتی محدود کننده یا پریکاردیت انقباضی، برون ده قلبی به بازگشت وریدی بستگی دارد. نیتروگلیسیرین داخل وریدی در بیماران مبتلا به این شرایط منع مصرف دارد. مصرف نیتروگلیسیرین در بیمارانی که فشار داخل جمجمه آنها افزایش یافته است منع مصرف دارد. در بیمارانی که از داروهای خاصی برای اختلال نعوظ (مهارکننده های فسفودی استراز) مانند سیلدنافیل، تادالافیل یا واردنافیل استفاده می کنند، از نیتروگلیسیرین در تزریق دکستروز 5 درصد استفاده نکنید. مصرف همزمان می تواند باعث افت فشار خون شدید، سنکوپ یا ایسکمی میوکارد شود. در بیمارانی که از ریوسیگوات محرک گوانیلات سیکلاز محلول استفاده می کنند از نیتروگلیسیرین در تزریق دکستروز 5 درصد استفاده نکنید. مصرف همزمان می تواند باعث افت فشار خون شود.
هشدارها
استفاده از لوله پی وی سی (پلی وینیل کلراید) در مجموعه های تزریق ممکن است منجر به از دست دادن ماده فعال به دلیل جذب نیتروگلیسیرین به لوله PVC شود، بنابراین دوز تحت تأثیر قرار می گیرد (دوز و تجویز را ببینید). جذب نیتروگلیسیرین توسط لوله PVC زمانی افزایش می یابد که لوله طولانی باشد، سرعت جریان پایین باشد و غلظت نیتروگلیسیرین محلول بالا باشد. کسر تحویلی از محتوای نیتروگلیسیرین اصلی محلول در مطالعات منتشر شده با استفاده از لوله PVC 20-60٪ بوده است. کسر با زمان در طول یک انفوزیون تغییر می کند و هیچ فاکتور اصلاحی ساده ای را نمی توان استفاده کرد. لوله PVC در اکثر مطالعات منتشر شده در مورد نیتروگلیسیرین داخل وریدی استفاده شده است، اما دوزهای گزارش شده با ضرب سرعت جریان محلول در غلظت اولیه نیتروگلیسیرین در محلول محاسبه شده است. دوزهای واقعی تحویل داده شده کمتر و گاهی بسیار کمتر از موارد گزارش شده بوده است. مجموعه های تزریق داخل وریدی نسبتاً غیرجذب در دسترس هستند. اگر نیتروگلیسیرین داخل وریدی از طریق لوله های غیرجذب تجویز شود، دوزهای مبتنی بر گزارش های منتشر شده عموماً بسیار بالا خواهند بود. برخی از فیلترهای داخل وریدی نیز نیتروگلیسیرین را جذب می کنند. باید از این فیلترها اجتناب کرد. محلول های حاوی دکستروز بدون الکترولیت نباید از طریق همان مجموعه تجویزی خون تجویز شوند، زیرا ممکن است منجر به شبه آگلوتیناسیون یا همولیز شود. تجویز داخل وریدی محلول ها ممکن است باعث بارگیری بیش از حد مایع شود که منجر به رقیق شدن غلظت الکترولیت های سرم، هیدراتاسیون بیش از حد و حالت های احتقانی ادم ریوی می شود. خطر حالت های رقیق شدن با غلظت الکترولیت تزریق ها نسبت معکوس دارد. خطر اضافه بار املاح که باعث ایجاد حالت های احتقانی همراه با ادم محیطی و ریوی می شود، به طور مستقیم با غلظت الکترولیت تزریق ها متناسب است.
احتیاط‌ها
Severe hypotension and shock may occur with even small doses of nitroglycerin. Monitor patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia and increased angina pectoris. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy. Tolerance development and occurrence of cross tolerance to other nitro compounds have been reported. In industrial workers who have long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence. Some clinical trials in angina patients have provided nitroglycerin for about 12 continuous hours of every 24-hour day. During the nitrate-free intervals in some of these trials, anginal attacks have been more easily provoked than before treatment, and patients have demonstrated hemodynamic rebound and decreased exercise tolerance. The importance of these observations to the routine, clinical use of intravenous nitroglycerin is not known. Lower concentrations of Nitroglycerin in 5% Dextrose Injection increase the potential precision of dosing, but these concentrations increase the total fluid volume that must be delivered to the patient. Total fluid load may be a dominant consideration in patients with compromised function of the heart, liver, and/or kidneys. Administer nitroglycerin in 5% Dextrose Injection via an infusion pump that can maintain a constant infusion rate. Intracoronary injection of Nitroglycerin in 5% Dextrose Injection has not been studied. Monitor patients with known sub-clinical or overt diabetes mellitus when using solutions containing dextrose. Laboratory Tests: Because of the propylene glycol content of intravenous nitroglycerin, serum triglyceride assays that rely on glycerol oxidase may give falsely elevated results in patients receiving this medication. Drug Interactions: The vasodilating effects of nitroglycerin may be additive with those of antihypertensives (e.g., beta-blockers, calcium channel blockers and tricyclic antidepressants) and may cause increased hypotensive effects.. Concomitant use of Nitroglycerin in 5% Dextrose Injection with phosphodiesterase inhibitors (e.g. sildenafil, tadalafil, or vardenafil) can cause hypotension and is contraindicated (see CONTRAINDICATIONS ). Concomitant use of Nitroglycerin in 5% Dextrose Injection with riociguat, a soluble guanylate cyclase stimulator, can cause hypotension and is contraindicated (see CONTRAINDICATIONS ). Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. Nitroglycerin at higher dosages may interfere with the anticoagulant effect of heparin. Intravenous nitroglycerin can induce heparin resistance. Administration of Nitroglycerin in 5% Dextrose Injection through the same infusion set as blood can result in pseudoagglutination and hemolysis. Do not mix Nitroglycerin in 5% Dextrose Injection with any other medication of any kind. Carcinogenesis, Mutagenesis, and Impairment of Fertility: Animal carcinogenesis studies with injectable nitroglycerin have not been performed. Rats receiving up to 434 mg/kg/day of dietary nitroglycerin for 2 years developed dose-related fibrotic and neoplastic changes in liver, including carcinomas, and interstitial cell tumors in testes. At high dose, the incidences of hepatocellular carcinomas in both sexes were 52% vs. 0% in controls and incidences of testicular tumors were 52% vs. 8% in controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin was not tumorigenic in mice. Nitroglycerin was weakly mutagenic in Ames tests performed in two different laboratories. Nevertheless, there was no evidence of mutagenicity in an in vivo dominant lethal assay with male rats treated with doses up to about 363 mg/kg/day, p.o., or in in vitro cytogenetic tests in rat and dog tissues. In a three-generation reproduction study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day for six months prior to mating of the F0 generation with treatment continuing through successive F1 and F2 generations. The high-dose was associated with decreased feed intake and body weight gain in both sexes at all matings. No specific effect on the fertility of the F0 generation was seen. Infertility noted in subsequent generations, however, was attributed to increased interstitial cell tissue and aspermatogenesis in the high-dose males. In this three-generation study there was no clear evidence of teratogenicity. Pregnancy: Animal teratology studies have not been conducted with nitroglycerin injection. Teratology studies in rats and rabbits were conducted with topically applied nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day, respectively, and no toxic effects on dams or fetuses were seen. There are no adequate and well-controlled studies in pregnant women. Nitroglycerin should be given to a pregnant woman only if clearly needed. Nursing Mothers: It is not known if nitroglycerin is present in human milk or if nitroglycerin has effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for nitroglycerin and any potential adverse effects on the breastfed child from nitroglycerin or from the underlying maternal condition. Pediatric Use: Safety and effectiveness in the pediatric population have not been established. However, the relationship between hemodynamic effects of nitroglycerin and dose in the pediatric population have been documented in the literature. Studies in the literature used doses of nitroglycerin injection in pediatric patients ranging from 0.5 to 5 mcg/kg/min. The following equation can be used to calculate the flow rate in mL/hour of nitroglycerin using the 100 mcg/mL (25 mg/250 mL) concentration of nitroglycerin. Infusion Rate (mL/h) = [Dose (mcg/kg/min) x Weight (kg) x 60 min/h] Final Concentration (mcg/mL) Example calculations for infusion rates are as follows: Example 1: for a 2 kg child at a dose of 0.5 µg/kg/min using a 100 mcg/mL concentration, the infusion rate would be as follows: Infusion Rate (mL/h) = [0.5 (mcg/kg/min) x 2 (kg) x 60 (min/h)] = 0.6 (mL/h) 100 (mcg/mL) Example 2: for a 10 kg child at a dose of 5 mcg/kg/min using a 100 mcg/mL concentration, the infusion rate would be as follows: Infusion Rate (mL/h) = [5 (mcg/kg/min) x 10 (kg) x 60 (min/h)] = 30 (mL/h) 100 (mcg/mL) Note: Very low infusion rates may require that a more dilute concentration of nitroglycerin infusion solution be prepared. Geriatric Use: Clinical studies of Nitroglycerin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Do not use unless vacuum is present and solution is clear.
عوارض جانبی
Adverse reactions to nitroglycerin are generally dose-related and almost all of these reactions are the result of nitroglycerin's activity as a vasodilator. Headache, which may be severe, is the most commonly reported side effect. Headache may be recurrent with each daily dose, especially at higher doses. Transient episodes of lightheadedness, occasionally related to blood pressure changes, may also occur. Hypotension occurs infrequently, but in some patients it may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina, and rebound hypertension have been reported but are uncommon. Allergic reactions to nitroglycerin are also uncommon, and the great majority of those reported have been cases of contact dermatitis or fixed drug eruptions in patients receiving nitroglycerin in ointments or patches. There have been a few reports of genuine anaphylactoid reactions, and these reactions can probably occur in patients receiving nitroglycerin by any route. Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients. Methemoglobinemia is so infrequent at these doses that further discussion of its diagnosis and treatment is deferred (see OVERDOSAGE ). Dyspnea has also been reported. Data are not available to allow estimation of the frequency of adverse reactions during treatment with Nitroglycerin in 5% Dextrose Injection.
مصرف بیش از حد
Signs and symptoms of overdose are generally similar to the described adverse reactions (see ADVERSE REACTIONS ). There is no specific antidote for overdose of nitroglycerin. The risk of overdose can be minimized by close monitoring during treatment. Hemodynamic Effects: The ill effects of nitroglycerin overdose are generally the results of nitroglycerin's capacity to induce vasodilation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and death. Laboratory determinations of serum levels of nitroglycerin and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of nitroglycerin overdose. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of nitroglycerin and its active metabolites. Similarly, it is not known which -if any- of these substances can usefully be removed from the body by hemodialysis. No specific antagonist to the vasodilator effects of nitroglycerin is known, and no intervention has been subject to controlled study as a therapy of nitroglycerin overdose. Because the hypotension associated with nitroglycerin overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward increase in central fluid volume. Passive elevation of the patient's legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary. The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good. In patients with renal disease or heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of nitroglycerin overdose in these patients may be subtle and difficult, and invasive monitoring may be required. Methemoglobinemia: Nitrate ions liberated during metabolism of nitroglycerin can oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moieties of nitroglycerin are quantitatively applied to oxidation of hemoglobin, about 1 mg/kg of nitroglycerin should be required before any of these patients manifests clinically significant (≥ 10%) methemoglobinemia. In patients with normal reductase function, significant production of methemoglobin should require even larger doses of nitroglycerin. In one study in which 36 patients received 2-4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr, the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo. Cases of methemoglobinemia have been reported with moderate doses of organic nitrates. Methemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air. When methemoglobinemia is diagnosed, discontinue treatment of nitroglycerin. If condition is not reversed, treat with methylene blue, 1-2 mg/kg intravenously.
توضیحات
Nitroglycerin is 1,2,3-propanetriol trinitrate, an organic nitrate whose structural formula is whose empiric formula is C3H5N3O9, and whose molecular weight is 227.09. The organic nitrates are vasodilators, active on both arteries and veins. Dextrose (Dextrose Hydrous, USP) is D-glucose monohydrate, a hexose sugar whose structural formula is whose empiric formula is C6H12O6
- H2O, and whose molecular weight is 198.17. Dextrose is derived from corn. Nitroglycerin in 5% Dextrose Injection is a sterile, nonpyrogenic solution of nitroglycerin and dextrose in water for injection. The solution is clear and practically colorless. Each 100 mL contains 10 mg, 20 mg, or 40 mg nitroglycerin (added as Diluted Nitroglycerin, USP with propylene glycol); 5 g Dextrose Hydrous, USP; 0.84 mL Alcohol, USP (added as a dissolution aid); and 105 mg Citric Acid Hydrous, USP (added as a buffer). The pH of the solution is adjusted with sodium hydroxide and, if necessary, hydrochloric acid. Although dry nitroglycerin is explosive, nitroglycerin in 5% dextrose is not. Composition, osmolarity and pH are given in Table 1. * Normal physiologic osmolarity range is approximately 280 to 310 mOsmol/L. Administration of substantially hypertonic solutions (≥600 mOsmol/L) may cause vein damage. STRUCTURE 1 STRUCTURE 2 DESCRIPTION
فارماکولوژی بالینی
The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins, especially the latter. Dilatation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined. Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continuously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials have used exercise testing to assess the anti-anginal efficacy of continuously-delivered nitrates. In the large majority of these trials, active agents were indistinguishable from placebo after 24 hours (or less) of continuous therapy. Attempts to overcome nitrate tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their anti-anginal efficacy been restored. Pharmacokinetics: The volume of distribution of nitroglycerin is about 3 L/kg, and nitroglycerin is cleared from this volume at extremely rapid rates, with a resulting serum half-life of about 3 minutes. The observed clearance rates (close to 1 L/kg/min) greatly exceed hepatic blood flow; known sites of extrahepatic metabolism include red blood cells and vascular walls. The first products in the metabolism of nitroglycerin are inorganic nitrate and the 1,2-and 1,3- dinitroglycerols. The dinitrates are less effective vasodilators than nitroglycerin, but they are longer-lived in the serum, and their net contribution to the overall effect of chronic nitroglycerin regimens is not known. The dinitrates are further metabolized to (non-vasoactive) mononitrates and, ultimately, to glycerol and carbon dioxide. To avoid development of tolerance to nitroglycerin, drug-free intervals of 10-12 hours are known to be sufficient; shorter intervals have not been well studied. In one well-controlled clinical trial, subjects receiving nitroglycerin appeared to exhibit a rebound or withdrawal effect, so that their exercise tolerance at the end of the daily drug-free interval was less than that exhibited by the parallel group receiving placebo. Clinical Trials: Blinded, placebo-controlled trials of intravenous nitroglycerin have not been reported, but multiple investigators have reported open-label studies, and there are scattered reports of studies in which intravenous nitroglycerin was tested in blinded fashion against sodium nitroprusside. In each of these studies, therapeutic doses of intravenous nitroglycerin were found to reduce systolic and diastolic arterial blood pressure. The heart rate was usually increased, presumably as a reflexive response to the fall in blood pressure. Coronary perfusion pressure was usually, but not always, maintained. Intravenous nitroglycerin reduced central venous pressure (CVP), right atrial pressure (RAP), pulmonary arterial pressure (PAP), pulmonary-capillary wedge pressure (PCWP), pulmonary vascular resistance (PVR), and systemic vascular resistance (SVR). When these parameters were elevated, reducing them toward normal usually caused a rise in cardiac output. Conversely, intravenous nitroglycerin usually reduced cardiac output when it was given to patients whose CVP, RAP, PAP, PCWP, PVR, and SVR were all normal. Most clinical trials of intravenous nitroglycerin have been brief; they have typically followed hemodynamic parameters during a single surgical procedure. In one careful study, one of the few that lasted more than a few hours, continuous intravenous nitroglycerin had lost almost all of its hemodynamic effect after 48 hours. In the same study, patients who received nitroglycerin infusions for only 12 hours out of each 24 demonstrated no similar attenuation of effect. These results are consistent with those seen in multiple large, double-blind, placebo-controlled trials of other formulations of nitroglycerin and other nitrates.