The efficacy of transdermal fentanyl in the treatment of postoperative pain: a double-blind comparison of fentanyl and placebo systems

Forty consenting patients scheduled for abdominal surgery were entered into a double-blind comparison of the efficacy of transdermal fentanyl (TTS-fentanyl) and placebo (TTS-placebo) in the treatment of postoperative pain. All patients were allowed supplementary pethidine (25-50 mg) if pain relief was inadequate provided that their respiratory rate was greater than 10 breaths/min and there was no pronounced CNS depression. Visual analogue pain scores (VAPS), sedation rating scores (SRS), blood samples for the determination of fentanyl concentration, blood pressure, pulse and respiratory rate were determined hourly for 48 h from the time of TTS system application. The first lot of TTS systems were removed after 24 h and a second lot were applied which remained in situ for a further 24 h. There was no significant difference between the patients in the TTS-fentanyl and TTS-placebo groups in the VAPS throughout the 0-12, 12-24, 24-36 and 36-48 h periods suggesting that the quality of pain relief was similar between the 2 groups. However, significantly less supplementary pethidine was administered to the TTS-fentanyl group in the 12-24, 24-36 and 36-48 h periods. In contrast, the amount of supplementary pethidine administered in the 0-12 h period was similar in both groups which was consistent with the long delay time (mean +/- S.D. value of 16.6 +/- 10 h) before clinically effective concentrations of fentanyl were obtained from the systems. The profile of side effects was similar in the 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atenolol and chlorthalidone therapy for hypertension: a double-blind comparison

In a randomized, double-blind, parallel-group study of 31 patients with mild to moderate hypertension, we compared a placebo regimen with a regimen of atenolol and chlorthalidone (Tenoretic). The study, which lasted seven weeks, began with a single-blind two-week placebo lead-in period, followed by a four-week double-blind treatment phase, and concluded with a one-week single-blind placebo washout period. Of 24 patients included in the analysis of efficacy, seven received one Tenoretic 50 tablet per day (atenolol, 50 mg; chlorthalidone, 25 mg), nine received one Tenoretic 100 tablet per day (atenolol, 100 mg; chlorthalidone, 25 mg), and eight received placebo. Supine systolic/diastolic blood pressure (mean +/- SD) decreased from 154 +/- 15.2/102 +/- 4.6 mm Hg during the baseline period to 128 +/- 8.5/85 +/- 4.0 mm Hg during treatment in the group receiving Tenoretic 100, from 153 +/- 12.6/104 +/- 5.4 mm Hg to 137 +/- 4.5/91 +/- 4.4 mm Hg in the group receiving Tenoretic 50, and from 150 +/- 11.9/101 +/- 1.6 mm Hg to 145 +/- 11.6/93 +/- 5.1 mm Hg in the group receiving placebo. Reductions in systolic and diastolic blood pressures in the active treatment groups were significantly greater than the pressure reductions in the group receiving placebo (P less than .05 to .1). The combination of atenolol and chlorthalidone was well tolerated, and in no case was treatment discontinued because of side effects. This study showed that one tablet per day of either Tenoretic 50 or Tenoretic 100 is effective and well tolerated in the treatment of mild to moderate hypertension.     

Pancreaticobiliary disorders: comparison between magnetic resonance cholangiopancreatography images before and after fentanyl injection

Objective

This study was designed to determine the effects of intravenous fentanyl on magnetic resonance cholangiopancreatography image quality in the treatment of pancreaticobiliary disorders.

Materials and methods

Forty consecutive patients referred for the evaluation of pancreaticobiliary disorders underwent magnetic resonance cholangiopancreatography in the coronal and oblique–coronal planes before and after fentanyl injection (every 2 up to 9 min). The images were analyzed qualitatively and quantitatively. Diameter and signal intensity were measured at the widest point and distal to the common bile duct and main pancreatic duct.

Results

The mean common bile duct diameters at the widest and distal points and mean pancreatic duct diameter were measured 7.53, 4.72, and 2.14 and 8.33, 5.35, and 2.57 before and after fentanyl injection, respectively. Mean signal intensity at the widest and distal point of the common bile duct and mean pancreatic duct signal intensity measured 278, 199, and 113 and 296, 218, and 121 before and after fentanyl injection, respectively. Minor improvements in image quality were detected qualitatively.

Conclusion

Fentanyl injection improves images qualitatively and quantitatively. In agreement with previous studies, our results confirm the beneficial effects of fentanyl as a simple adjunct to traditional magnetic resonance cholangiopancreatography.     

A comparison of alpha-methylnorepinephrine,vasopressin and epinephrine for cardiac resuscitation

The objective of this research was to compare the effects of an alpha- and beta-adrenergic agonist, epinephrine, a selective alpha(2)-adrenergic agonist, alpha-methylnorepinephrine (alpha-MNE), and a non-adrenergic vasopressin on post-resuscitation myocardial function and duration of survival. Epinephrine continues to be the primary adrenergic agent for advanced cardiac life support. However, its major inotropic actions and especially its beta-adrenergic and, to a lesser extent, its alpha(1)-actions increase the severity of global ischemia during cardiac arrest and adversely affect post-resuscitation myocardial function and survival. We had previously observed significantly better outcomes with a selective alpha(2)-adrenergic agonist when compared with epinephrine. Non-adrenergic vasopressin also has promise of more favorable actions. The present study was, therefore, undertaken to compare a selective alpha(2)-adrenergic vasopressor drug with vasopressin, epinephrine, and saline placebo. Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. Mechanical ventilation and precordial compression were initiated after 8 min of untreated VF. About 2 min later, alpha-MNE in a dose of 100 microgram/kg, vasopressin in a dose of 0.4 U/kg, epinephrine in a dose of 30 microgram/kg, or saline control was administered. Defibrillation was attempted after 6 min of CPR. Left ventricular pressure, dP/dt(40), -dP/dt, and cardiac index were measured for an interval of 240 min after resuscitation. Except for saline controls, comparable increases in coronary perfusion pressure (CPP) were observed after each drug intervention. All animals were successfully resuscitated. Post-resuscitation myocardial function and survival were significantly better in animals treated with alpha-MNE. Both post-resuscitation myocardial function and survival were most improved after administration of the selective alpha(2)-adrenergic agonist, intermediate after vasopressin and least after epinephrine and saline placebo.     

A comparison of transoesophageal cardiac pacing and epinephrine for cardiopulmonary resuscitation

The use of cardiac pacing to deal with bradycardia is well established. There is debate as to the benefits during cardiopulmonary resuscitation (CPR). This study was performed to compare the effects of transoesophageal cardiac pacing and high-dose epinephrine on the benefits of cardiopulmonary resuscitation after asphyxial cardiac arrest in rats. Thirty Sprague-Dawley rats of both sexes were randomly selected to a saline group (Sal-gro, treated with normal saline 1 mL IV, n = 10), an epinephrine group (Epi-gro, treated with epinephrine 0.4 mg/kg IV, n = 10), or a pacing group (Pac-gro, treated with normal saline 1 mL IV combined with transoesophageal cardiac pacing, n = 10) in a blinded fashion during resuscitation after 10 minutes of asphyxial cardiac arrest. Manual chest compression was in all cases performed using the same methodology by the same personnel who was blinded to hemodynamic monitor tracings. The rate of restoration of spontaneous circulation was 1 (10%), 7 (70%), and 8 (80%) of 10 in Sal-gro, Epi-gro, and Pac-gro, respectively. The rate of ventilator withdrawal within 60 minutes after resuscitation in Pac-gro was higher than that of Epi-gro (8/8 vs 1/7, respectively; P = .001); the survival rate after 2 hours in Pac-gro was significantly higher than that in Epi-gro (7/8 vs 1/7, respectively; P = .01). The data demonstrate that both epinephrine and transoesophageal cardiac pacing are effective within 10 minutes of asphyxia in rats. It is worth noting that transoesophageal cardiac pacing produced a better outcome with respiration and longer survival time compared with epinephrine after restoration of spontaneous circulation.     

Efficacy of low-dose nebulized epinephrine as treatment for croup: A randomized,placebo-controlled,double-blind trial

ObjectiveCroup treatment usually involves a single dose of systemic dexamethasone combined with nebulized epinephrine. However, the optimal dose of l-epinephrine remains unclear. We examined whether a low dose (0.1 mg/kg) was inferior to the conventional dose (0.5 mg/kg) of 1:1000 nebulized l-epinephrine in patients with moderate to severe croup.MethodsThis randomized double-blind clinical non-inferiority trial was conducted in three pediatric emergency departments from May 2015 to October 2017. Children 6 months to 5 years old with moderate to severe croup (Westley scale scores 3–11) were eligible. Subjects were randomly assigned to the conventional dose (0.5 mg/kg: maximum 5 mg) or low dose (0.1 mg/kg; maximum 1 mg) group. All subjects received 0.6 mg/kg dexamethasone. Croup scores and other vital signs were measured before and at 30, 60, 90, and 120 min after nebulized l-epinephrine administration. The primary outcome was the change in croup score after 30 min.ResultsThe final analysis included 84 patients. The groups did not differ significantly in terms of demographic parameters. At 30 min after treatment with nebulized l-epinephrine, the croup scores in both groups were significantly reduced from the baseline values (p < 0.05) and did not differ between the two groups (p = 0.42). Neither blood pressure nor heart rate differed between the two groups.ConclusionsLow-dose 1:1000 l-epinephrine was not inferior in croup score reduction to the conventional dose in patients with moderate to severe croup.Clinical trial No: NCT01664507, KCT0002318.     

Accidental injection of epinephrine by a child: a unique approach to treatment

A 9-year-old girl accidentally injected her right thumb with an adult dose of epinephrine through an auto-injector syringe, delivering 0.3 mg of 1:1000 epinephrine. This injection caused immediate ischemic changes in the digit. This is the first reported case of accidental self injection by a child of an adult dose of epinephrine and its successful treatment with low-dose phentolamine simultaneously infiltrated directly into the puncture area and along the course of the digital artery. The use of phentolamine as a specific competitive alpha-adrenergic antagonist to epinephrine has been well documented in adults and animal models. This report compares the management of a pediatric case to that of all reported adult cases of accidental subcutaneous epinephrine injections. This case suggests a pattern of infiltration with low-dose phentolamine that may be the most effective form of treatment for this condition in a patient of any age.     

Diclofenac sodium in ureteral colic: a double-blind comparison trial with placebo

A randomized prospective double blind study of the analgesic effect of 75 mg intramuscular diclofenac sodium (Voltaren), a potent prostaglandin synthetase inhibitor, versus placebo (saline solution) was carried out in 131 consecutive patients with acute ureteral colic. Diclofenac provided complete relief of pain 25 minutes after the injection in 59% of the cases, while placebo provided relief in 29% (p less than 0.01). Forty patients in the placebo group and seventeen patients in the diclofenac group needed an open injection of 75 mg diclofenac intramuscularly after 25 minutes due to persistent pain. Fifty-four of the fifty-seven patients treated with an open injection of diclofenac achieved complete relief of pain after 30 minutes. There were no side-effects of the treatment.     

A comparison of epinephrine and norepinephrine in critically ill patients

Objective  To determine whether there was a difference between epinephrine and norepinephrine in achieving a mean arterial pressure (MAP) goal in intensive care (ICU) patients. Design  Prospective, double-blind, randomised-controlled trial. Setting  Four Australian university-affiliated multidisciplinary ICUs. Patients and participants  Patients who required vasopressors for any cause at randomisation. Patients with septic shock and acute circulatory failure were analysed separately. Interventions  Blinded infusions of epinephrine or norepinephrine to achieve a MAP ≥70 mmHg for the duration of ICU admission. Measurements  Primary outcome was achievement of MAP goal >24 h without vasopressors. Secondary outcomes were 28 and 90-day mortality. Two hundred and eighty patients were randomised to receive either epinephrine or norepinephrine. Median time to achieve the MAP goal was 35.1 h (interquartile range (IQR) 13.8–70.4 h) with epinephrine compared to 40.0 h (IQR 14.5–120 h) with norepinephrine (relative risk (RR) 0.88; 95% confidence interval (CI) 0.69–1.12; P = 0.26). There was no difference in the time to achieve MAP goals in the subgroups of patients with severe sepsis (n = 158; RR 0.81; 95% CI 0.59–1.12; P = 0.18) or those with acute circulatory failure (n = 192; RR 0.89; 95% CI 0.62–1.27; P = 0.49) between epinephrine and norepinephrine. Epinephrine was associated with the development of significant but transient metabolic effects that prompted the withdrawal of 18/139 (12.9%) patients from the study by attending clinicians. There was no difference in 28 and 90-day mortality. Conclusions  Despite the development of potential drug-related effects with epinephrine, there was no difference in the achievement of a MAP goal between epinephrine and norepinephrine in a heterogenous population of ICU patients. This study was presented at the Annual Congress of the European Society of Intensive Care Medicine in Berlin on October 10 2007. The presentation received the International Sepsis Forum prize for best abstract and paper. This study has been published in abstract form: Myburgh J.A., Higgins A., Jovanovska A., Lipman J., Ramakrishnan N., Santamaria J and the CAT Study Investigators. (2007). A comparison of epinephrine and norepinephrine on reversal of shock. Intensive Care Medicine 33 (Supplement 2): S197. Trial registration: The study was registered with Current Controlled Studies: ISRCTN number 92846592.     

舒芬太尼与芬太尼用于剖宫产术后静脉镇痛的比较

目的观察比较舒芬太尼与芬太尼应用于剖宫产术后患者自控静脉镇痛的效果及安全性。方法选择ASA评分Ⅰ~Ⅱ级,在连续硬膜外麻醉下行剖宫产术的患者600例,随机分为舒芬太尼组(S组)和芬太尼组(F组)2组,术后行自控静脉镇痛,镇痛药分别为舒芬太尼1μg/mL,芬太尼10μg/mL,比较自控镇痛的效果与不良反应。结果 2组均可获得有效的镇痛效果,但F组的不良反应较多,恶心呕吐发生率较高。结论舒芬太尼用于剖宫产术后静脉镇痛安全有效,副反应较少并且能明显改善产妇泌乳,提高母乳喂养的成功率。     

Intravenous maprotiline in severe and resistant primary depression: a double-blind comparison with clomipramine

A double-blind, randomized trial is described which was designed to compare the clinical effect of 100 mg daily of maprotiline (Ludiomil) and of clomipramine (Anafranil) given by the intravenous route in forty hospitalized female patients with severe and resistant primary depression. Physicians' assessment of patients' progress was made following 5, 9 and 21 days of treatment. The response rates to maprotiline and clomipramine were not significantly different even if a greater number of patients responded to clomipramine. None of the demographic and clinical variables considered could be identified as factor predicting the response to maprotiline and to clomipramine, even if a trend for a preferential responsiveness to clomipramine in the older patients was observed.     

A double-blind comparison of bisoprolol and atenolol in patients with essential hypertension

We compared the ß₁-selective adrenoceptor antagonistsbisoprolol and atenolol in a double-blind, randomized crossoverstudy. After 4 weeks placebo phase, 59 patients with essentialhypertension received either 10 mg bisoprolol or 50 mg atenololonce daily for 8 weeks, increased if necessary (target BP 150/90mmHg) to 20 and 100 mg, respectively, after 4 weeks. After asecondplacebo phase, crossover occurred to the alternative drug. Wemeasured resting systolicand diastolic blood pressures and heartrate at 24 h post-dose baseline and after 4 and 8 weeks treatment.Both drugssignificantly lowered systolic and diastolic bloodpressures and heart rate at 8 weeks compared to baseline (allp <0.05). Bisoprololreduced heart ratesignificantly morethan atenolol (p <0.01), but systolic and diastolic bloodpressure changes were not different between the two drugs. Therewas no difference in patient acceptability of the drugs as assessedby visual analogue scale. Despite theoreticaland circumstantialevidence to suggest superiority of bisoprolol over atenolol,no significant difference between the two was found except forgreater heart rate reduction with bisoprolol.     

Comparing intranasal ketamine with intravenous fentanyl in reducing pain in patients with renal colic: A double-blind randomized clinical trial

BackgroundKidney stones are a fairly common problem that manifests itself as symptoms of acute abdominal and flank pains in patients presenting to emergency departments.ObjectiveThe present study was conducted to compare the analgesic effect of intravenous fentanyl with that of intranasal ketamine in renal colic patients.MethodsOne mg/kg of intranasal ketamine was administered in the first group, and one μg/kg of intravenous fentanyl in the second group. The pain severity was measured in the patients in terms of a visual analogue scale (VAS) score at the beginning of the study and at minutes 5, 15 and 30, and the medication side-effects were evaluated and recorded.ResultsA total of 130 patients were ultimately assessed in two groups of 65. In the ketamine group, the mean severity of pain was 8.72 ± 1.52 at the beginning of the study (P < 0.001), 5.5 ± 2.97 at minute 5 (P < 0.001), 3.38 ± 3.35 at minute 15 (P = 0.004) and 2.53 ± 3.41 at minute 30 (P = 0.449). In the fentanyl group, this severity was 9.66 ± 88.8 in the beginning of the study (P < 0.001), 7.27 ± 1.37 at minute 5 (P < 0.001), 4.61 ± 1.5 at minute 15 (P = 0.004) and 1.24 ± 1.25 at minute 30 (P = 0.449). The general prevalence of the medication side-effects was 10 (15.4%) in the ketamine group and 1 (1.5%) in the fentanyl group (P = 0.009).ConclusionsKetamine was found to be less effective than fentanyl in controlling renal colic-induced pain, and to be associated with a higher prevalence of side-effects; nevertheless, ketamine can be effective in controlling this pain in conjunction with other medications.