The role of age in determining the effects of lipo-PGE1 infusion on immediate arterial maximal flow velocity in patients with diabetes undergoing free flap surgery for lower extremity reconstruction: A prospective observational study.

BACKGROUND: Diabetes mellitus may have a negative effect on free flap perfusion in patients undergoing reconstructive surgery. Little is known of the effects of lipo-prostaglandin E1 (lipo-PGE1) on flap blood flow in diabetes. This study investigated the effects of lipo-PGE1 on maximal blood flow velocity of the free flap arterial pedicle in patients with diabetes. METHODS: This prospective observational study assessed maximal blood flow velocity in the arterial pedicle before and 30 min after infusion of 0.4 µg/h lipo-PGE1 in 40 patients with diabetes who received a free flap for lower extremity reconstruction. Multivariate logistic regression analysis was performed to determine whether age, hemoglobin A1c concentration, duration of diabetes, and flap type were significantly associated with increased maximal blood flow velocity after lipo-PGE1 infusion or not. RESULTS: The maximal blood flow velocity of the free flap did not differ significantly before and 30 min after lipo-PGE1 infusion. Multivariate logistic regression analysis showed that age <65 years was the only independent factor associated with increased maximal blood flow velocity after lipo-PGE1 infusion (odds ratio = 5.344; p = 0.022). CONCLUSION: Assessments of all patients with diabetes undergoing free flap surgery, when age was not taken into consideration, found that lipo-PGE1 did not significantly increase the maximal blood flow velocity of the free flap arterial pedicle. However, when age was taken into consideration, lipo-PGE1 increased blood flow velocity in patients <65 years old, suggesting that age influences the effect of lipo-PGE1 on the blood flow velocity.

Lipo-prostaglandin E1 increases immediate arterial maximal flow velocity of free flap in patients undergoing reconstructive surgery.

BACKGROUND: In free flap surgery, the maintenance of proper blood flow after anastomosis of flap pedicle vessels is important. Lipo-prostaglandin E1 (lipo-PGE1) has been empirically administered to prevent blood flow insufficiency in a free flap reconstruction. We tested our hypothesis that lipo-PGE1 administration increases the arterial inflow of free flap. We also evaluated lipo-PGE1-related haemodynamic changes and complications. METHODS: Thirty-seven patients who underwent free flap reconstruction were analysed. Lipo-PGE1 was administered 10 minutes after the vascular anastomosis of the free flap. The maximal blood flow velocity was measured at the free flap pedicle artery before and 30 minutes after lipo-PGE1 administration using duplex ultrasonography. The primary outcome was the difference in the maximal blood flow velocity before and 30 minutes after lipo-PGE1 administration. The arterial blood pressure, heart rate, cardiac output, stroke volume variation, and pulse pressure variation were measured simultaneously. Lipo-PGE1-related complications such as hypotension, bradycardia, hypothermia, facial flushing, diarrhoea, apnoea, and seizure were also investigated. RESULTS: The maximal blood flow velocity was significantly increased at 30 minutes after lipo-PGE1 administration compared to the level before lipo-PGE1 administration (mean (standard deviation): 26.3 (8.7) cm/s vs 22.5 (8.0) cm/s, P = 0.002). The haemodynamic variables were not significantly different before and 30 minutes after lipo-PGE1 administration. No lipo-PGE1-related complications occurred. CONCLUSIONS: Lipo-PGE1 significantly increases the maximal blood flow velocity without complications in patients undergoing free flap reconstruction and may be an effective and safe method of maintaining adequate blood flow in these cases.

Continuous infusion of lipo-prostaglandin E1 for Takayasu's arteritis with heart failure in an 11-month-old baby: a case report.

BACKGROUND: Takayasu's arteritis is extremely rare in children aged below 6 years. At the onset of Takayasu's arteritis in children, symptoms are varied but differ from those in adults. Corticosteroids are the mainstay of treatment for preventing irreversible vascular damage but there is no standard treatment for progressive vascular stenosis. CASE PRESENTATION: A Japanese 11-month-old baby boy presented with Takayasu's arteritis and heart failure, possibly due to afterload mismatch caused by high blood pressure. Computed tomography was performed and revealed thoracic and abdominal aortic aneurysms. It also revealed severe celiac artery stenosis and bilateral renal artery stenosis. Prednisolone was initiated as first-line therapy. The fever resolved, and C-reactive protein levels returned to normal. Although his general condition improved, deterioration of vascular lesions was evident. Celiac artery occlusion, severe right renal artery stenosis, and new superior mesenteric artery stenosis were observed. We decided to use a continuous infusion of lipo-prostaglandin E1 for prevention of branch stenosis of his abdominal aorta. The progression of vascular stenosis was stopped and our patient's cardiac function gradually improved. CONCLUSIONS: A differential diagnosis of heart failure with high blood pressure should be considered in babies. The progression of vascular stenosis may be suppressed by lipo-prostaglandin E1.

Clinical efficacy of different doses of lipo-prostaglandin E1 in the treatment of painful diabetic peripheral neuropathy.

OBJECTIVE: To observe the clinical efficacy of different doses of alprostadil (lipo-prostaglandin E1, lipo-PGE1) in the treatment of painful diabetic peripheral neuropathy (DPN). METHODS: Sixty patients with painful DPN were equally and randomly assigned into three groups. Two groups received different doses of lipo-PGE1 by intravenous drip injection (A group: low-dose lipo-PGE1; B group: high-dose lipo-PGE1) following intravenous bolus injection of mecobalamin (MeCbl, 0.5mg once daily (QD)); the third group received MeCbl alone (C group). All patients received optimized treatment to lower blood glucose, blood pressure, and blood lipids to target levels. The efficacy of lipo-PGE1 in the three groups of patients was observed after 3weeks of treatment. RESULTS: The overall response rate was 90% in the B group, significantly higher than that in the A and C groups (80% and 55%, respectively; P<0.05). During the observation period, there was no incidence of serious adverse reactions (e.g., acute heart failure, sudden drop in blood pressure, or malignant arrhythmias) in any of the three groups. CONCLUSIONS: High-dose lipo-PGE1 has better efficacy than low-dose lipo-PGE1 or MeCbl alone in the treatment of painful DPN.

Effects of lipo-prostaglandin E1 on wound bed microcirculation.

OBJECTIVE: Lipo-prostaglandin E1 (lipo-PGE1) is a well-known potent vasodilator that increases peripheral blood flow. However, the effects of this agent on wound bed microcirculation still remain unclear. The present study aims to improve the experimental model which our group developed to visualise wound bed microcirculation and to evaluate acute stimulation by lipo-PGE1. METHOD: The superficial stratum of the Wistar rat's ear skin was microsurgically excised preserving the subdermal vascular plexus. The preserved vessels, the wound bed microcirculation, were visualised under an intravital microscope-video-computer system. Animals were divided into three groups, a control group in which animals received vehicle control, a medium-dose group (6 µg/2 ml/kg lipo-PGE1) and a high-dose group (10 µg/2 ml/kg lipo-PGE1). The blood velocity and diameter of individual venules were measured from the recorded microcirculatory images, and the blood flow of the venule in the wound bed was evaluated. RESULTS: A significant increase in the wound bed blood flow was seen 10 minutes after lipo-PGE1 injection (p<0.05). This was approximately fourfold the baseline values. The increase was greatest in the medium-dose group. Extravasation and accumulation of lipo-PGE1 in the wound bed was observed. CONCLUSION: Lipo-PGE1 effectively increased wound bed microcirculation blood flow at the optimal dose. DECLARATION OF INTEREST: There is no conflict of interest.

Therapeutic Effects of Carbogen Inhalation and Lipo-Prostaglandin E1 in Sudden Hearing Loss

PURPOSE: Vascular disorders and viral infections are considered the main causes of sudden hearing loss (SHL), although its pathogenesis remain unclear. Treatments include carbogen inhalation and lipo-prostaglandin E1 (lipo-PGE1), both of which have circulation-enhancing effects. We investigated the effectiveness of carbogen inhalation and lipo-PGE1 in SHL. MATERIALS AND METHODS: This retrospective review included 202 patients with idiopathic SHL who visited our clinic within 14 days of symptom onset between January 2006 and June 2010. All patients received oral prednisolone for 10 days. Of the 202 patients, 44 received no additional treatment, 106 received additional carbogen inhalation, and 52 received additional lipo-PGE1. Hearing improvement was measured using Siegel's criteria. RESULTS: Overall recovery rates were 67.9% in the carbogen group, 53.8% in the lipo-PGE1 group, and 52.3% in the steroid-only control group (p=0.097). Limited to type 1 and type 2 categories of Sigels's criteria, the carbogen group had a significantly higher recovery rate (53.8%) than the lipo-PGE1 group (26.9%) and the steroid-only control group (38.6%) (p=0.005). CONCLUSION: Carbogen inhalation added to steroid was a more effective treatment than lipo-PGE1 added to steroid or steroid alone in patients with SHL.

Prostaglandin E1 used as a pre-operative treatment for the neonates with transposition of great vessels with intact ventricular septum / 中华急诊医学杂志

Objective To study the therapeutic effects of prostaglandin E1 on the neonates with transposition of the great vessels with intact ventricular septum (TGV/IVS) retrospectively. Method From January 2004 to June 2009, 34 neonates with TGV/IVS were enrolled in this study. The pulse rate and oxygen saturation (SpO2) of patients were measured percutaneouly at admission. Lipo-prostaglandin E1 (Lipo-PGE1) was administered via peripheral vein with pumping infusion continuously after diagnosis by echocardiography in order to keep the ductus arteriosus (DA) patent. The dose and the time required for the Lipo-PGEl to produce effect were recorded. The changes of SpO2 before and after administration of Lipo-PGE1 were observed. The changes of DA's diameter detected by using echocardiography before and during the operation. Results In all patients the initial dose of Lipo-PGEl was 5 ng/( kg·min) except 3 patients whom larger dosed were required to give guided by the change of SpO2 with 10 ng/(kg·min) in two patients and 15 ng/(kg·min) in one patient. The time required for Lipo-PGE to produce the effect was 5-15 minutes in most infants with mean of (12 ± 3) minutes. The mean SpO2 of the patients measured at admission was (80.05±7.64)%, and it was (86.41±4.83)% two hours before operation (P < 0.05). The average diameter of DA was (0.37±0.08) cm at the time diagnosis and it was (0.51 ±0.15) cm during the operation. The adverse effects occurred in two patients and one of them had apnea and was treated mechanical ventilation. Conclusions Lipo-PGE1 given by continuous pumping infusion via peripheral vein in dose of 5 ng per kilogram per minute can maintainthe DA patency and promote the systemic oxygenation and perfusion, improving the circulation and oxygenation and correcting the acidosis until the plastic surgery performed. Most of the adverse effects of PGE1 are dose related.

Analysis of Therapeutic Effects of Lipo-Prostaglandin E1 for Treatment of Sudden Sensorineural Hearing Loss in Patients with Type 2 Diabetes / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES : Diabetes mellitus (DM) is a risk factor for sudden sensorineural hearing loss (SSNHL), possibly due to microvascular damage as well as increased blood viscosity and embolic and thrombotic episodes. To perform a prospective, randomized clinical trial to evaluate the therapeutic effect of lipo-prostaglandin E(1) (lipo-PGE(1)) on SSNHL in Korean patients with type 2 diabetes. MATERIALS AND METHOD : The study group consisted of 270 patients (130 males, 140 females) consecutively diagnosed with SSNHL. Patients were classified as diabetic or nondiabetic by the new American Diabetes Association criteria. With the approval of the institute ethics committee, patients were randomly assigned to treatment with a continuous infusion of 10 L lipo-PGE(1) (lipo-PGE(1) group) or saline (placebo group). In addition, all patients studied were treated with 48 mg methylprednisolone for 5 days. RESULTS : The overall recovery rates after treatment were 51.5% in diabetic and 64.2% in nondiabetic patients. In diabetic patients, there was a significantly higher rate of hearing improvement in the lipo-PGE(1) group (64.7%) than in the placebo group (37.5%), whereas, in nondiabetic patients, there was no significant difference in the rate of hearing improvement between the lipo-PGE(1) group (70.3%) and the placebo group (58.3%). CONCLUSION : Lipo-PGE(1) may have beneficial effects in the treatment of SSNHL in Korean patients with type 2 diabetes.

The Effect of Lipo-PGE1 According to the Routes of Administration on the Survival of Transverse Rectus Abdominis Musculocutaneous Flap in Rats

The Transverse rectus abdominis musculocutaneous (TRAM) flap has been commonly used for autologous breast reconstruction. Despite these clinical usefulness, the TRAM flap is prone to partial flap or fat necrosis in especially pedicled flap. To improve flap survival, the surgical delay procedures and pharmacological treatments have been developed. In many studies for the pharmacological treatment, Lipo-PGE1 has demonstrated a marked ability to improve flap survival and it's effect has been proved similar to surgical delay procedure. The purpose of this study is to determine the most effective route of Lipo-PGE1 administration as a pharmacological treatment in TRAM flap of the rat. Fifty male Sprague-Dawley rats weighing 300-350 gm were divided into five groups, One week before flap elevation, Lipo- PGE1(2 microgram/kg) was injected three times in a week and than the left inferior epigastric vessel based TRAM flap (5.0x3.0 cm) elevated; group I: no procedure before flap elevation; group II: intraperitoneal injection; group III: intravenous injection; group IV: subcutaneous injection; group V: topical application. A flap was assessed at postoperative 7 days by comparison of flap survival rate, vessel counts(H-E stain), and vascular endothelial growth factor(VEGF) protein expressed by Western blot. The results demonstrated that the mean percentages of the flap survival area in group III were significantly higher than that of any other group(p<0.05). The vessel counts of all experimental groups were statistically higher than that of control group(p<0.05). Only in group III, the VEGF protein expression was increased significantly than control group and there are no difference in other experimental groups. In conclusion, the intravenous administration of the Lipo-PGE1 is the most effective on flap survival, and the VEGF induced by Lipo-PGE1 has some positive effects on new vessel formation and flap survival.

Delay Phenomenon by Lipo-PGE1 in Single Perforator-based Abdominal Skin Flap of Rat

The perforator based flap has been used successfully as a pedicle or free flap and has gained popularity in clinical use. Although Lipo-PGE1 effect on survival rate of musculocutaneous flap is good, but effect on survival rate of perforator based flap is not well known. Therefore, the purpose of this study is to find pharmacological delay effect by using Lipo-PGE1 in abdominal skin perforator flap of rats. Thirty Sprague- Dawley rats were divided into 3 groups. Perforator flaps were designed in rectangular shape, sized 3x7cm to 4x8 cm on abdomen. Flap incision was made deeply enough to the panniculus carnosus, from lateral to medial side and we found four musculocutaneous perforators at each side. Right second cranial perforator was saved, and the others were electrocauterizied. The experimental groups included group I(control): no procedure before the flap elevation; group II(surgical delay): right second cranial perforator was saved, one week before the flap elevation, the others cauterizied. But left four perforators were not injuried.; Group III(pharmacological delay): before the flap elevation, Lipo-PGE1(0.5microgram) was given intraperitoneally for 5 days. On the seventh day after operation, the results were evaluated and compared in terms of flap survival area, vessel counts by Hematoxylin-Eosin stain and Vascular Endothelial Growth Factor (VEGF) protein expression by Western blot. The results were as followings. First, The mean percentages of the flap survival area in Group II(83.75+/-11.07%) and Group III(76.95+/-11.99%) were significantly higher than that in Group I(44.06+/-15.29%)(p<0.05). Second, The vessel counts of Group II(4.4+/-0.84) and Group III(4.3+/-0.82) were significantly higher than that of Group I(2.0+/-0.67) significantly(p<0.05) Third, The VEGF expression is increased in two experimental groups than that of control group. In conclusion, the use of Lipo-PGE1 could increase flap survival area in rat skin perforator flap model, as likely as surgical delay. This phenomenon is thought to be due to choke vessel dilatation and new vessel formation. Therefore, we expect that Lipo-PGE1 can increase rate of flap survivability in perforator based flap as well as that of musculocutaneous flap, only short term use.

The Effect of Duration of Lipo-PGE1 Administration on Flap Survival in a Rat TRAM Model

This study was designed to find out an effective duration of pharmacological delay using Lipo-PGE1 to prevent the ischemic compromise of TRAM flap in rats. Fifty Sprague-Dawley rats were divided into 5 groups evenly and a left inferior epigastric vessel pedicled TRAM flap, sized 5.0 X 3.5 cm was created on the abdomen. Experimental groups included group I(control): no procedure before the flap elevation; group II, III, IV and V(pharmacological delay groups): Lipo-PGE1(0.5mug) was given daily intraperitoneally for 3, 5, 7 and 14 days before the flap elevation. On the seventh day after the operation, we evaluated and compared the results of flap survival rate, vessel distribution through Barium microangiography and histological findings by the hematoxylin-eosin stain and the VEGF immunohistochemistry. The results were as follow: 1) The mean percentage of the flap survival area of group II(52.84 +/-27.03%), III(63.15+/- 16.57%), IV(63.53+/- 13.15%), V(61.44+/- 17.17%) were higher than that of group I(30.42 +/- 14.58%) significantly (p < 0.05). 2) The vessel distribution of the pharmacologic delay groups were more abundant than that of the control group. 3) the vascularity of the pharmacological delay groups were more diffused than that of the control group in the hematoxylin-eosin stain. 4) There was no difference in the expression of VEGF protein within the endothelial cell between the control and the pharmacological delay groups. In conclusion, the use of Lipo-PGE1 for a relatively short term period(about 3-5 days) could remarkably increase the flap survival area in rat TRAM model compared to the surgical delay(2 weeks).

The Effects of Lipo Prostaglandin E1(Eglandin ) in Patients with Ductus Dependent Congenital Heart Disease

PURPOSE: The adverse reactions of prostaglandin E1(PGE1) are troublesome in the preoperative management of critical patients with ductus dependent congenital heart disease, and a preparation with less adverse reactions is preferable. The effects of Lipo PGE1, a new preparation of PGE1 contained in lipid microspheres, were compared with those of conventional PGE1(PGE1-CD). METHODS: Lipo PGE1 was infused at a rate of 5 ng/kg/min in 19 patients, PGE1-CD at a rate between 10 and 50 ng/kg/min in 15 patients. The effects of drugs were assessed in terms of clinical response rate and overall safety. RESULTS: Clinically, both treatment were effective in relieving cyanosis and hypoxemia except in patients already having either a closed ductus or severe hypoxemia and acidosis. The increments of PaO2 1 hour after infusion were 10.9 and 6.2 mmHg (p>0.1), respectively and those 4 hours postinfusion were 16.0 and 7.8 mmHg(p0.1), the mean dose of Lipo PGE1 at appearance of response was about 1/5 of that of PGE1-CD in overall patients and also in patients with ductus dependent pulmonary circulation(6.7 vs 31.7 ng/kg/min, p<0.005). The adverse reactions occurred in 52.6% of the patients given Lipo PGE1, while it was 86.7% in those administered PGE1-CD(p<0.05). The adverse reactions in Lipo PGE1 group was much less severe than that in PGE1-CD group. There was a significant difference in overall safety between the two drugs(84.2 vs 40%, p<0.01). As the incidence of the adverse reactions increased at dose over 5 ng/kg/min, the initial dose of 5 ng/kg/min seemed to be appropriate for Lipo PGE1. CONCLUSIONS: Lipo PGE1 was effective at a lower dose than was PGE1-CD, and was associated with fewer or less severe adverse reactions, and is therefore judged to be more suitable for clinical use than conventional PGE1-CD.