The prevention of CDDP-induced emesis with a combination regimen including metoclopramide, dexamethasone, droperidol and diphenhydramine

The dose limiting factors of cisplatinum are nephrotoxicity and emesis. Nephrotoxicity has been reduced by hydration but nausea and vomiting caused by cisplatinum have led to refusal of potentially curative therapy by a number of patients. The prevention of nausea and vomiting by a combination of antiemetic drugs administered to ovarian patients receiving chemotherapy inducing (cisplatinum 50mg/m2, adriamycin 300 mg/m2, cyclophosphamide 300 mg/m2 and 5FU 350 mg/m2) was studied. the combination antiemetic drugs were metoclopramide (1mg/kg), dexamethasone (10mg/m2), droperidol (1mg/m2) and diphenhydramine (20mg/body). These drugs without diphenhydramine were administered intravenously 30 minutes before and 2.5 hours, 5 hours and 7.5 hours after chemotherapy. Diphenhydramine was administered intramuscularly 30 minutes before and 5 hours after chemotherapy. No vomiting was noted in 82.6% (19/23) of cases, and no patient vomited more than four times. This combination regimen provided very good protection against cisplatinum induced emesis.     

Antiemetic combination for PAC (cisplatin-adriamycin-cyclophosphamide) chemotherapy-induced emesis in ovarian cancer

Twenty-six patients suffering from disseminated epithelial ovarian cancer (FIGO stages III and IV) under treatment with Cisplatin (80-100 mg/m2 in 8 hours) in combination on the same day with Cyclophosphamide (500 mg/m2 IV) and Adriamycin (50 mg/m2), a severely emetogenic regimen, entered a randomized, double-blind, cross-over trial comparing the antiemetic activity of high-dose IV Metoclopramide (1 mg/kg/dose X 5 doses) with that of a combination of Metoclopramide (same schedule) plus Nortriptyline (50 mg PO X 2 doses) plus Thiethylperazine (10 mg IV X 3 doses). The antiemetic combination was designed in an attempt to act simultaneously on gastrointestinal motility and neuroreceptors at the central emetic pathways (dopamine D-2, histamine H-1 and muscarinic cholinergic). This combination significantly reduced the emesis due to chemotherapy when compared with Metoclopramide alone and was also preferred by a significant number of patients after passing through both the antiemetic arms being compared.     

Antiemetic efficacy of high-dose metoclopramide, diphenhydramine, methylprednisolone and diazepam on chemotherapy-induced emesis in gynecological malignancy

The antiemetic efficacy of high-dose metoclopramide (MCP), diphenhydramine (DPH), methylprednisolone (MPL), and diazepam (DZP) was investigated in 40 gynecologic cancer patients for a total of 98 chemotherapy courses, treated with cisplatin (50 mg/m2). With MPL (500 mg i.v. x 2) plus DZP (5 mg i.m. x 2), no vomiting occurred in 0% and mild emesis (vomiting 1-2 times) occurred in 20% of 25 courses. With MCP (2 mg/kg i.v. x 5) plus DPH (40 mg i.v. x 3), no vomiting occurred in 35% and mild emesis occurred in 10% of 20 courses. With a combination of MCP plus DPH and MPL plus DZP, no vomiting occurred in 51% and mild emesis occurred in 25% of 53 courses. These results indicate that high-dose MCP plus DPH are effective in preventing cisplatin-induced vomiting. Furthermore, the antiemetic efficacy of MCP plus DPH (0-2 vomiting episodes: 45%) was significantly enhanced (p less than 0.05) by the combined use of MPL plus DZP (0-2 vomiting episodes: 76%).     

The use of methylprednisolone and metoclopramide in control of emesis in patients receiving cis-platinum

cis-Platinum is a chemotherapeutic agent with benefits often limited by the severe gastrointestinal reactions it produces in nearly all patients. Persistent anorexia, nausea, and vomiting may continue for days after therapy and are poorly controlled by conventional antiemetics. Patients at times refuse continuation of cis-platinum chemotherapy because of these severe gastrointestinal side effects. Intravenous methylprednisolone (Solu-medrol) as well as intravenous metoclopramide (Reglan) have been shown effective in the treatment of chemotherapy-induced nausea and vomiting. This randomized, double-blind study is a comparison of the efficacy of Solu-medrol vs Reglan, as well as, the combination of Solu-medrol and Reglan in the prevention of cis-platinum-induced nausea and vomiting. In this study patients receiving Reglan had better protection from vomiting than patients receiving Solu-medrol (P = 0.0564). Patients receiving the combination of Reglan and Solu-medrol had better protection from vomiting than patients receiving Reglan alone (P = 0.0332), or patients receiving Solu-medrol alone (P = 0.0010). Finally, older patients experienced less vomiting than younger patients, regardless of the anti-emetic drugs used (P = 0.0730).     

Antiemetic efficacy of high-dose corticosteroids and droperidol in cisplatin-induced emesis: A controlled trial with droperidol and metoclopramide

The nausea and vomiting associated with cisplatin chemotherapy make care of the patient more difficult for nurses and physicians, can cause severe metabolic and pathologic sequelae, and preclude further courses of chemotherapy. Current reports suggest that the two most efficacious agents for antiemetic prophylaxis are metoclopramide and corticosteroids. These two agents in combination with droperidol have been compared in a randomized controlled prospective fashion. Patients had less nausea and vomiting on the steroidal regimen than the nonsteroidal regimen (P less than 0.05), and the duration of nausea and vomiting was significantly less on the steroidal regimen (P less than 0.05). Patients expressed a preference for the steroidal regimen over the nonsteroidal one and the steroidal regimen retained its antiemetic effectiveness through repeated courses of chemotherapy. The results of the study suggest that corticosteroids and droperidol are superior antiemetic agents for cisplatin-induced nausea and vomiting.     

The effect of dexamethasone therapy in prolonged pregnancy

Fifty-six patients, chosen by random sampling from a total group of 120 post-term women, received dexamethasone (Decadron, "MSD" 2 mg 3 times a day for 4 days, the other 64 patients acting as controls. The evolution of uterine activity was evaluated using pelvic score (PS) and a modified low dosage oxytocin sensitivyt test (OST) before (T1) and after (T2) the treatment. During the interval from the second to the 6th day inclusive after T1 35 women of the dexamethasone group and 15 of the control group had a spontaneous onset of labour (SO) (0.001 less than P less than 0.01). Five patients in the dexamethasone group with primary rupture of membranes started labour spontaneously within 12 hours after membrane rupture, 7 patients in the control group with primary rupture of membranes received oxytocin as labour did not start within 24 hours. Excluding patients artifically induced, the mean interval from T1 to SO was 6.8 days in the control group and 5.2 days in the dexamethasone group (P less than 0.001). In both groups PS and the sum of Montevideo units (MU) during OST increased from T1 to T2, the increase was significantly greater in the dexamethasone group than in the control group. We found no correlation between the results of OST and the T1--SO interval. Dexamethasone, as used in this study, may promote labour in prolonged human pregnancy. Due to its low potency, it is not a substitute for oxytocin in the induction of labour. The lowered placento-fetal quotient in the dexamethasone group warrants further study of the effects of steroid hormone on placental function.     

The effect of naloxone and metoclopramide on the hypothalamic pituitary axis in oligomenorrheic and eumenorrheic swimmers

Eight highly competitive swimmers were followed over a 9-month period during a vigorous training schedule. When compared, four oligomenorrheic (group I, greater than 60 days without menses) and four eumenorrheic (group II) swimmers were not significantly different for age, years of training, body fat, intensity of training, and baseline estradiol (E2) levels. Both groups were challenged during the peak of their training schedule with 10 mg of naloxone and 10 mg of metoclopramide. The naloxone infusion revealed a significant increase in baseline luteinizing hormone (LH) levels in the oligomenorrheic swimmers when compared with the eumenorrheic swimmers. During the metoclopramide infusion prolactin (PRL) increased in all subjects, with a slightly higher increase in PRL in the eumenorrheic swimmers. The study suggests the menstrual dysfunction observed in these strenuously training swimmers to be related to the abnormalities of endorphin physiology as revealed by the elevation in LH after a naloxone infusion.     

The effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome in preterm gestations with premature rupture of membranes

A prospective blinded randomized study was carried out to determine the effect of antepartum administration of dexamethasone on the incidence of respiratory distress syndrome in 250 patients with gestations between 28 and 33 weeks complicated by premature rupture of membranes. The incidence of respiratory distress syndrome was not lowered by the length of rupture of membranes in the 124 untreated patients. The overall incidence of respiratory distress syndrome was reduced from 51% to 25% by the administration of corticosteroids. Further, the dexamethasone-treated group had a statistical significant reduction in the incidence of intraventricular hemorrhage, total time of hospitalization, and average cost per patient. No statistical difference was encountered in the incidence of maternal or neonatal sepsis.     

The effect of photobiomodulation on chemotherapy-induced peripheral neuropathy: A randomized,sham-controlled clinical trial

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy with few efficacious treatments.

促性腺激素释放激素激动剂对化疗损伤卵巢功能保护作用的实验研究

目的研究促性腺激素释放激素激动剂(GnRHa)对注射环磷酰胺(CTX)大鼠的卵巢功能的保护作用。方法80只Fischer344大鼠分为4组,即空白对照组、GnRHa组、CTX组及联合治疗组,每组20只,分别接受生理盐水、CTX、GnRHa和CTX+GnRHα注射,采用酶联免疫吸附实验和化学发光法测定各组大鼠卵泡刺激素(FSH)和雌二醇浓度的变化,在实验开始后第60、90天,各组分别处死一半大鼠,观察卵巢重量、卵泡数量及卵泡直径的变化。结果实验第90天,CTX组大鼠血清雌二醇和FSH浓度分别为(148·3±16·5)pmol/L和(16·90±1·90)U/L,明显高于联合治疗组的(91·8±9·9)pmol/L和(7·60±0·30)U/L,两组分别比较,差异有统计学意义(P<0·05);CTX组大鼠卵巢重量为(37·0±3·0)mg,低于联合治疗组的(71·0±5·0)mg,两组比较,差异有统计学意义(P<0·05);CTX组大鼠卵泡总数为(550±50)个,而联合治疗组为(1250±160)个,两组比较,差异有统计学意义(P<0·05)。结论GnRHa能够降低CTX对大鼠卵巢功能的损伤,从而保护大鼠卵巢储备功能。     

The effect of antenatal dexamethasone on maternal and fetal retinol-binding protein

Sixteen rhesus monkeys received 0.1 to 15 mg/kg of antenatal dexamethasone at 132 days' gestation; seven control animals received placebo. At 135 days' gestation they underwent cesarean section, and maternal and fetal serum was assayed for retinol-binding protein. Fetal and maternal concentrations of retinol-binding protein increased after dexamethasone (p less than 0.05) and there was a trend for fetal levels of retinol-binding protein to increase with increasing dosage (p less than 0.01). Whether the elevation of retinol-binding protein in response to antenatal dexamethasone is a desirable side effect is not clear at this time.     

Routine use of dexamethasone for the prevention of postextubation respiratory distress

We evaluated the routine use of dexamethasone for the prevention of postextubation respiratory distress by entering 60 ventilated infants into a prospective, randomized, blinded study. Thirty minutes before extubation, 30 infants were given a single dose of intravenous dexamethasone (0.25 mg/kg), and 30 infants received saline placebo. Infants were intubated orotracheally for at least 48 hours following a single intubation and were maintained on low ventilator settings (F10(2) less than 0.35, intermittent mandatory ventilation [IMV] less than 6, positive end-expiratory pressure [PEEP] less than 4) at least 12 hours before extubation. Following extubation, all infants weighing less than 1500 g were routinely placed on nasal continuous positive airway pressure (NCPAP). There was no difference between the two groups in postextubation Downes' score, serum pH, PCO2, or oxygen requirement at 30 minutes, 6 hours, and 24 hours. Respiratory acidosis occurred in one steroid-treated patient and in two placebo-treated infants. Stridor occurred in four infants in each group. No infant developed postextubation lobar atelectasis or required reintubation. We conclude that prophylactic administration of dexamethasone does not improve the immediate postextubation course of infants following a single intubation and that its routine use at the time of extubation is not indicated.     

GnRHa和避孕药保护化疗所致卵巢损伤的比较研究

目的:探讨促性腺激素释放激素激动剂(GnRHa)和口服避孕药(OC,达英-35)对注射环磷酰胺(CTX)大鼠卵巢功能的保护作用。方法:实验分为6组:空白对照组、CTX组、OC组、GnRHa组、OC保护组、GnRHa保护组,每组15只,分别接受生理盐水、CTX、达英-35、GnRHa、达英-35+CTX、GnRHa+CTX注射或灌胃。阴道涂片观察大鼠动情周期,以放射免疫法检测血清雌二醇(E2)和卵泡刺激素(FSH)浓度,每组在停药当天、15天及30天分别处死5只大鼠,观察卵巢重量、卵巢结构及各级卵泡数目。结果:停药后30天,OC保护组和GnRHa保护组的E2浓度分别为51.33±2.00pg/ml、44.38±5.98pg/ml,FSH浓度分别为3.69±0.28mIU/ml、3.35±0.22mIU/ml,两组比较及与空白对照组(51.76±2.57pg/ml、3.44±0.20mIU/ml)相比,差异均无统计学意义;与CTX组(21.78±2.11pg/ml、6.24±0.22mIU/ml)比较,差异有统计学意义。OC保护组和GnRHa保护组的卵巢重量、卵泡数量与空白对照组相比,差异无统计学意义,明显高于CTX组,两组间比较差异亦无统计学意义。结论:GnRHa和口服避孕药均能减轻化疗药物对卵巢功能的损伤,从而保护卵巢储备功能。     

The effect of betamethasone versus dexamethasone on fetal biophysical parameters.

BACKGROUND: Clinical observations suggest that betamethasone reduces maternal perception of fetal movements and short term variability, but that this dose not occur after treatment with dexamethasone. OBJECTIVES: To compare the effect of betamethasone and dexamethasone on fetal biophysical parameters. METHODS: In a randomized, prospective, double blind study, 20 courses of betamethasone and 20 courses of dexamethasone were given in random sequence to patients with imminent preterm labor. During the first 32h after initiation of treatment, fetal movements were counted by the mothers and recorded by ultrasound, and a nonstress test was performed. RESULTS: Betamethasone induced a significant decrease in fetal movements as perceived by the mother and observed by ultrasound. Fetal breathing movements also decreased. Dexamethasone did not change fetal body movements. Neither drug changed the short term variability. CONCLUSIONS: Unlike betamethasone, dexamethasone does not induce a decrease in fetal movements. Dexamethasone might, therefore, be preferred for enhancement of lung maturation in imminent preterm labor.     

The effect on the fetal pituitary-adrenal axis of dexamethasone administration early in the second trimester of pregnancy

Objective.?To evaluate the effect of a single dose of dexamethasone to pregnant women at early second trimester on the fetal pituitary-adrenal axis.

Methods.?Thirty-eight women between 13 and 15 weeks' gestation were included in the study. Blood was taken from the mothers and their fetuses for the evaluation of plasma ACTH, cortisol, and free cortisol levels before and after treatment with a single dose of 1?mg of dexamethasone orally at 11 p.m. the night before the termination of pregnancy.

Results.?The mean plasma ACTH was significantly lower following dexamethasone administration (8.5?±?5.1 vs. 18.4?±?10.9 pg/ml). Similarly, plasma cortisol was significantly lower after dexamethasone treatment (208.3?±?168.7 vs. 772.7?±?206.1?nmol/l), as well as plasma free cortisol levels (2.6?±?0.0 vs. 6.1?±?6.1?nmol/l). Mean plasma ACTH levels were not significantly different in the fetuses after dexamethasone treatment (33.6?±?22.7 vs. 42.5?±?21.9 pg/ml). Moreover, mean fetal plasma cortisol was not different before and after treatment (108.2?±?27.2 vs. 94.3?±?47.2?nmol/l), as well as the mean free cortisol levels (7.7?±?5.2 vs. 7.0?±?4.3?nmol/l).

Conclusions.?A single dose of 1?mg of dexamethasone to the mother early in the second trimester of pregnancy does not result in a significant suppression of the fetal pituitary axis.     

The effect of metoclopramide on ovarian responsiveness to gonadotropin administration in patients with severe polycystic ovarian syndrome

Six patients with poor ovarian response to menotropin after pretreatment with a gonadotropin-releasing hormone analog exhibited improved ovarian responsiveness when metoclopramide was added on days 3, 5, and 7 of the cycle. This was evidenced by a higher number of leading follicles (4.4 versus 0.6), a higher mean of maximal serum 17 beta-estradiol levels (560 versus 178 pg/mL), a shorter duration of menotropin treatment (7 versus 11 days), and fewer ampules of menotropin used (20 versus 37 ampules/cycle) in metoclopramide-treated cycles as compared with control cycles, respectively. Serum prolactin levels reached a maximum of 172 ng/mL within 1 hour after metoclopramide administration and declined to normal range within 6 hours. These results suggest that intermittent increased prolactin secretion may augment ovarian response to gonadotropins.