Razi Journal of Medical Sciences

fa استفاده از داروهای اینودیلاتور (Inodilators) برای درمان سندرم برون ده قلبی پایین (LCOS) بعد از جراحی قلب در کودکان Use of inodilators for the treatment of low cardiovascular syndrome (LCOS) after cardiac surgery in children قلب کودکان Pediatric Cardiology مروري review article زمینه و هدف: اگرچه میزان عوارض و مرگ ومیر پس از جراحی قلب کودکان در طی دهه‌های اخیر به صورت چشمگیری کاهش یافته است. ولی سندرم برون ده قلبی پایین (LCOS) همچنان به عنوان یکی از عوارض شایع جراحی قلب کودکان مطرح می‌باشد و در 25% کودکانی که تحت عمل جراحی قلب قرار می‌گیرند دیده می شود. عوارض LCOS شامل مدت زمان طولانی اینتوباسیون-مدت زمان طولانی بستری در بیمارستان و افزایش ریسک ایجاد عفونت و در نهایت مرگ می‌باشد. اصول کلی درمان LCOS عبارت است از: کنترل صحیح پره لود قلب و تنظیم صحیح دستگاه تهویه مکانیکی به همراه استفاده از داروهایی که به طور همزمان اثرات اینوتروپیک مثبت و کاهنده مقاومت عروق سیستمیک و ریوی را دارند (Inodilators). روش کار: ما مطالعات مختلفی راجع به اثرات داروهای قلبی در LCOS به ویژه پس از عمل جراحی قلب کودکان مورد بررسی قرار دادیم. یافته‌ها: مطالعات اخیر نشان داده‌اند که LCOS با افزایش مقاومت عروق ریوی و سیستمیک ارتباط دارد. بنابراین دارو هایی که علاوه بر بهبود انقباض قلب و خاصیت اینو تروپیک بتوانند به طور همزمان مقاومت عروق ریوی و سیستمیک و کرونری را کاهش دهند (داروهای Inodilators) کلید اصلی پیشگیری و درمان LCOS می‌باشند.Milrinone  (مهارکننده فسفو دی استراز تیپ 3) و Levosimendan (حساس کننده کاردیومیوسیت‌ها به کلسیم) دو داروی اصلی اینو دیلاتور هستند که در حال حاضر برای پیشگیری و درمان LCOS بعد از انجام جراحی قلب استفاده می شوند. تجویز Levosimendan نه فقط بعد از عمل جراحی قلب بلکه در حین جراحی قلب و حتی قبل از جراحی قلب برای کودکانی که در خطر بالای ایجاد LCOS بعد از جراحی قلب هستند، مفید است. نتیجه گیری: Levosimendane همانند Milrinone در جلوگیری از ایجاد LCOS موثر بود.   Background: Complications and mortality after pediatric heart surgery have declined dramatically in recent decades, low cardiac output syndrome (LCOS) remains one of the most common complications of pediatric heart surgery, occurring in 25% of children undergoing Heart surgery. The most important complications of LCOS include prolonged  intubation, prolonged hospital stay, and increased risk of infection and death. Factors that predict the development of LCOS after open heart surgery include: 1) factors before heart surgery  for example the presence of ventricular dysfunction and heart failure,…2) factors during surgery  including the use of cardiopulmonary pump (CPB), hypothermia , type of Heart surgery, Use of cardioplegia, Myocardial ischemia during aortic clamp, Myocardial reperfusion injury, Acute systemic inflammatory syndrome (SIRS) and changes in systemic and pulmonary vascular resistance. Low cardiac output syndrome (LCOS) presents with symptoms of tachycardia, decreased diuresis, decreased systemic perfusion and metabolic acidosis.Therefore, early prevention and treatment of LCOS is very important. The general principles of treatment in LCOS are: Proper control of preload of  heart ,  control  of mechanical ventilation with the use of drugs that simultaneously have positive inotropic effects and reduce systemic and pulmonary vascular resistance, Drugs with this property are called inodilators Inodilators have positive inotropic effects (stronger myocardial contraction) , Lusitropic effects (relaxation or better expansion of the heart) as well as vasodilatory effects on systemic-pulmonary and coronary arteries simultaneously. Therefore, these drugs are the basis of prevention and treatment (LCOS) after heart surgery. Milrinone (phosphodiesterase inhibitor type 3) and Levosimendan (calcium myocyte sensitizers) are the two main Inodilators drugs currently available for LCOS are used after heart surgery. Methods: We have reviewed several studies on the effects of heart medications on LCOS, especially after pediatric heart surgery. Results: Levosimendan is a new drug that has been used to treat heart failure since 2000. The effects of this drug are through two main mechanisms on cardiomyocyt: Cardiomyocyte sensitizer to calcium, Opening potassium-dependent channels also Levosimendan has three simultaneous effects on the cardiovascular system through these two mechanisms: Positive inotropic effect (stronger myocardial contraction), Lusitropic effect (Relaxation or better expansion of the heart), Vasodilatory effect on systemic-pulmonary and coronary arteries. The usefulness of Levosimendan in the treatment (LCOS) after heart surgery has been proven in adults and children.  However, the use of this drug as a first-line treatment (LCOS) after heart surgery is expensive because of this reason limited. Levosimendan is well tolerated by patients and its most common side effects are headache (7-8%), hypotension (5-6%), hypokalemia (5%) and tachycardia.Hypotension and tachycardia can be controlled by giving proper fluid volume or prescribing vasopressors such as norepinephrine.  Studies on the effect of Levosimendan on increasing the risk of atrial fibrillation are contraverse It should be noted that Hypotension, tachycardia and hypokalemia are more common in children than adults. Levosimendan has a better effect on heart function in adults undergoing heart surgery than traditional inotropic drugs, improving the patient's hemodynamic function, reducing myocardial damage, and shortening the length of hospital stay. Despite the high prevalence of LCOS after pediatric heart surgery, but we have no consensus on the choice of inotropic drug for the treatment of LCOS. Traditional LCOS therapy is the use of catecholamines. Side effects of catecholamines include increased oxygen consumption in the heart, increased ventricular after load, Down-regulation of beta-adrenergic receptors, reduces the efficacy of these drugs. Due to these side effects, Inodilator such as Milrinone are used to treat LCOS after heart surgery.  In Europe, Milrinone is present in 70.7% of LCOS treatment regimens after heart surgery, and the combination of this drug with other inotropes is present in 64% of treatment regimens. The mechanism of Milrinone is inhibition of phosphodiesterase type 3 (PDE3), which increases the intracellular concentration of CAMP. CAMP activates protein kinase, increases the entry of extracellular calcium into the heart cell, and ultimately these effects Increases the activity of contractile proteins and improves the contractile power of the heart. The effect of Milrinone on peripheral and coronary arteries is secondary to the increase in CGMP in vascular wall smooth muscle cells.  These effects of Milrinone improve heart function without increasing myocardial oxygen consumption and without increasing ventricular loading. These effects are also independent of alpha and beta adrenergic receptors. More common complication of Milrinone is hypotension. The next complication is tachycardia, although there is controversy about of tachycardia as a side effect of milrinone. We have no evidence that Milrinone causes tachyarrhythmias. The next complication of Milrinone is thrombocytopenia. Therefore, the patient's platelets should be monitored during treatment with Milrinone. Although Milrinone-induced thrombocytopenia cannot be distinguished from thrombocytopenia due to cardiovascular bypass pump (CPB).  Other side effects of milrinone include seizures, oral intolerance, and delayed in PDA closure of preterm infants. Conclusion: Milrinone and Levosimenda are both effective drugs in treatmen of LCOS in children, however, due to the availability and lower price of Milrinon, the use of Milrinon is more common. Milrinone,Levosimendan, LCOS Milrinone, Levosimenda,LCOS (Low cardiac output syndrome) 141 152 http://rjms.iums.ac.ir/browse.php?a_code=A-10-4660-1&slc_lang=fa&sid=1 FEISAL rahimpour فیصل رحیم پور feisalrahimpoor@gmail.com 3900319475328460053401 3900319475328460053401 Yes mashhad university دانشگاه علوم پزشکی مشهد hossein shahzadi حسین شهزادی hossein.shahzadi@yahoo.com 3900319475328460053402 3900319475328460053402 No Shahid Rajaee Heart Center دانشگاه علوم پزشکی ایران