Patient-controlled sedation using propofol: randomized, double-blind dose refinement

This double-blind, randomized trial compared the onset of sedation with two patient-controlled sedation regimens, allowing a maximum of 16 or 25 mg min-1 propofol. Forty fit young patients presenting for elective surgery were asked to try to put themselves to sleep using the system. Onset times of sedative effect, slurred speech and amnesia were recorded. All patients achieved satisfactory sedation, and none became oversedated. Patients receiving 16 mg min-1 propofol were not reliably sedated within 5 min and took significantly longer to develop slurred speech and amnesia (P < 0.01 for both). We conclude that this maximum infusion rate does not produce amnesia or sedation rapidly enough to be clinically useful. A maximum infusion rate of 25 mg min-1 allowed rapid sedation in all patients without oversedation and may be an acceptable compromise between efficacy and safety.     

Pain relief following herniotomy: a double-blind randomized comparison between naproxen and placebo

Sixty consecutive out-patients were randomly assigned to have either a non-steroid anti-inflammatory drug (naproxen 500 mg) or an identical placebo administered as suppositories half an hour before unilateral herniotomy. Within 1.5 h after the end of surgery, pain scores were significantly improved in patients receiving naproxen (P less than 0.02). The long-term analgesic effect was measured indirectly by registering the postoperative requirement for supplementary analgesic doses of acetylsalicylic acid 1 g plus codeine 20 mg. The time elapsing before the first demand for additional analgesics was prolonged by median 1.5 h, and the need for further analgesic treatment during 24 h was significantly reduced (P less than 0.003) in the naproxen group (median, 2 doses) compared to the placebo group (median, 4 doses). No statistically significant difference was found between the groups with regard to the occurrence of side-effects.     

Preemptive antiemesis in patients undergoing modified radical mastectomy: oral granisetron versus oral ondansetron in a double-blind, randomized, controlled study

STUDY OBJECTIVE: To assess the efficacy of oral granisetron versus oral ondansetron for preemptive antiemesis in women undergoing modified radical mastectomy. DESIGN: Randomized, double-blind, controlled study. SETTING: Metropolitan hospital. PATIENTS: Ninety ASA physical status I and II hospitalized female patients, aged 18 to 65 y, scheduled for modified radical mastectomies. INTERVENTIONS: Patients were assigned to receive orally placebo, granisetron 2 mg, or ondansetron 4 mg (n = 30 in each group) 1 h before induction of anesthesia. A standard general anesthetic technique and postoperative analgesia were used. MEASUREMENTS: Postoperative nausea and vomiting and safety assessments were performed continuously 0 to 2, 2 to 6, 6 to 12, and 12 to 24 h after anesthesia. MAIN RESULTS: A complete response during 0 to 2 h after anesthesia was found in 43%, 63%, and 90% of patients who had received placebo, granisetron, or ondansetron, respectively; corresponding percentages of patients requiring rescue antiemetics were 40%, 17%, and 7%. Frequency of nausea and vomiting was low (less than 23%) after 2 h in the three groups. Observations of postoperative nausea and vomiting score and need for antiemetics at other time intervals (2 to 6, 6 to 12, and 12 to 24 h) were not significantly different among the three groups. CONCLUSION: Oral ondansetron 4 mg provided better preemptive antiemesis than oral granisetron 2 mg in the 2 h after modified radical mastectomy during general anesthesia.     

Treatment of postoperative nausea and vomiting with ondansetron: a randomized, double-blind comparison with placebo

Postoperative nausea and vomiting are common after recovery from general anesthesia. The antiemetic effect and safety of ondansetron, a selective serotonin type 3 (5-HT3) receptor antagonist, was determined in 36 patients suffering from nausea or vomiting during recovery from intravenous anesthesia by giving either a single intravenous dose of ondansetron (8 mg, n = 18) or placebo (n = 18) over 2-5 min in a randomized, double-blind manner. A "rescue" antiemetic was provided in case of continued vomiting or at the patient's request. Antiemetic efficacy was defined as no request for rescue antiemetic and/or no vomiting episode during the next 4 h. There was no significant difference in the demographic data between the groups. Administration of ondansetron or placebo had no significant effect on vital signs. Ondansetron was an effective antiemetic in 78% (14/18) and placebo was effective in 28% (5/18) of the patients. Laboratory studies 24 h later showed no signs of hematologic, hepatic, or renal alterations. Ondansetron at a dose of 8 mg administered intravenously over 2-5 min appears to be a safe and effective antiemetic for the treatment of nausea and/or vomiting after intravenous anesthesia.     

A randomized, double-blind comparison of ondansetron versus placebo for prevention of nausea and vomiting after infratentorial craniotomy

Ondansetron was compared with placebo for nausea and vomiting prophylaxis after fentanyl/isoflurane/relaxant anesthesia and infratentorial craniotomy. Eight milligrams intravenous ondansetron or vehicle was administered at skin closure. Nausea, emesis, and antiemetic use were recorded at 0, 0.5, 1, 4, 8, 12, 24, and 48 hours. There were no significant intergroup differences for nausea incidence at any interval, but cumulatively the placebo group was 3.2 times more likely to develop nausea during the first 12 hours (P = .04). Nausea incidence was bimodal in both groups, peaking during the first 1 to 4 hours. A nadir occurred at 8 to 12 hours, but nausea increased during the next 36 hours. By 48 hours, approximately 40% of patients in both groups were still nauseated. Reduced vomiting frequency was seen with ondansetron at 4, 8, 12, and 24 hours (P < .05). Despite rescue antiemetics, emesis occurred in an irregular pattern with episodes still observed in 35% of placebo patients at 48 hours. For ondansetron, emesis was infrequent for the first 12 hours but then a persistent increase was observed (48 hours, 22%). The incidence of rescue antiemetic use was 65% for both groups. There was no effect of gender. Nausea and vomiting are frequent and protracted after infratentorial craniotomy. Administration of single-dose ondansetron (8 mg intravenously) at wound closure was partially effective in reducing acute nausea and vomiting but had little delayed benefit. Scheduled prophylactic administration of antiemetic therapy during the first 48 hours after infratentorial craniotomy should be evaluated for efficacy and safety.     

Propofol injection pain in children: a prospective randomized double-blind trial of a new propofol formulation versus propofol with added lidocaine

Background. The incidence of pain on injection of propofol remainsunacceptably high in children, despite various strategies toreduce it. A new drug formulation of propofol has, in adultstudies, been reported to cause less injection pain comparedwith other propofol solutions. The aim of the present prospectiverandomized double-blind clinical trial was to compare the incidenceof pain-free injection following the use of this new formulationwith that following the use of propofol with added lidocainein children undergoing day case surgery. Methods. Eighty-three children (age range 2–18 yr) wererandomized to receive 3 mg kg^–1 of either Propofol-Lipuro®(propofol dissolved in a mixture of medium- and long-chain triglycerides[MCT–LCT]; group pL, n=42) or Diprivan® (propofoldissolved in long-chain triglycerides [LCT]) with added lidocaine(0.3 mg kg^–1) (group pD, n=41). A specially trained nurseanaesthetist assessed the occurrence of injection pain usinga four-graded pain scale. Results. Significantly fewer patients had an entirely pain-freepropofol injection in group pL (33.3%) than in group pD (61.0%)(P=0.016). Conclusions. A new MCT–LCT propofol formulation as a plainsolution was associated with a higher incidence of injectionpain than LCT propofol with added lidocaine when used for inductionof anaesthesia in children.     

Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo

OBJECTIVE: To investigate the efficacy and tolerability of a 3-month duration, twice a-year, intermittent treatment with oral chondroitin sulfate (CS) in knee osteoarthritis (OA) patients. DESIGN: A total of 120 patients with symptomatic knee OA were randomized into two groups receiving either 800mg CS or placebo (PBO) per day for two periods of 3 months during 1 year. Primary efficacy outcome was Lequesne's algo-functional index (AFI); secondary outcome parameters included VAS, walking time, global judgment, and paracetamol consumption. Radiological progression was assessed by automatic measurement of medial femoro-tibial joint space width on weight-bearing X-rays of both knees. Clinical and biological tolerability was assessed. RESULTS: One hundred and ten of 120 patients were included in the ITT analysis. AFI decreased significantly by 36% in the CS group after 1 year as compared to 23% in the PBO group. Similar results were found for the secondary outcomes parameters. Radiological progression at month 12 showed significantly decreased joint space width in the PBO group with no change in the CS group. Tolerability was good with only minor adverse events identically observed in both groups. CONCLUSION: This study provides evidences that oral CS decreased pain and improved knee function. The 3-month intermittent administration of 800mg/day of oral CS twice a year does support the prolonged effect known with symptom-modifying agents for OA. The inhibitory effect of CS on the radiological progression of the medial femoro-tibial joint space narrowing could suggest further evidence of its structure-modifying properties in knee OA.     

Target-controlled propofol vs. sevoflurane: a double-blind, randomised comparison in day-case anaesthesia

We compared target-controlled propofol with sevoflurane in a randomised, double-blind study in 61 day-case patients. Anaesthesia was induced with a propofol target of 8 microgram.ml-1 or 8% sevoflurane, reduced to 4 microgram.ml-1 and 3%, respectively, after laryngeal mask insertion and subsequently titrated to clinical signs. Mean (SD) times to unconsciousness and laryngeal mask insertion were significantly shorter with propofol [50 (9) s and 116 (33) s, respectively] than with sevoflurane [73 (14) s and 146 (29) s; p < 0.0001 and p = 0.0003, respectively]; however, these differences were not apparent to the blinded observer. Propofol was associated with a higher incidence of intra-operative movement (55 vs. 10%; p = 0.0003), necessitating more adjustments to the delivered anaesthetic. Emergence was faster after sevoflurane [5.3 (2.2) min vs. 7.1 (3.7) min; p = 0.027], but the inhaled anaesthetic was associated with more nausea and vomiting (30 vs. 3%; p = 0.006), which delayed discharge [258 (102) min vs. 193 (68) min; p = 0.005]. Direct costs were lower with sevoflurane but nausea would have increased indirect costs. Patient satisfaction was high (>/= 90%) with both techniques. In conclusion, both techniques had advantages and disadvantages for day-case anaesthesia.     

Microthrombus formation on hemodialysis membranes: a placebo controlled randomized trail of two doses of Indobufen

The role of Indobufen in preventing the formation of microthrombi on hemodialysis membranes has been investigated in 18 patients in a placebo controlled randomized double-blind cross-over study. All patients had been on regular maintenance hemodialysis for at least 3 months. Indobufen was given as 100 mg b.d. and 200 mg b.d. each for a 7 day period with a 7 day wash-out period between the treatments. Both Indobufen regimens prevented the fall in platelet count, reduced the increase in plasma BTg levels during dialysis, increased the post dialysis plasma heparin levels (p less than 0.05) and inhibited pre-dialysis platelet aggregation with collagen (p less than 0.05), when compared with placebo treatment. Scanning electron microscopy demonstrated minimal fibrin and reduced platelet deposition following Indobufen treatment. There was no difference in the effect of 100 mg b.d. and 200 mg b.d. Indobufen doses. The drug was well tolerated, despite the relatively high levels measured, only one patient withdrew because of side effects. This study indicates that Indobufen when added to a routine hemodialysis treatment schedule, can significantly reduce platelet activation and the thrombus formation on the hemodialysis membranes.     

Pain on injection: a double-blind comparison of propofol with lidocaine pretreatment versus propofol formulated with long- and medium-chain triglycerides

The incidence of pain on injection of propofol has been reported to be 70%. A new propofol formulation with a 10% emulsion of long- and medium-chain triglycerides (LCT/MCT) is associated with less pain on injection. Our goal was to compare the effect of propofol-LCT/MCT on the incidence of pain versus propofol with lidocaine 40 mg IV pretreatment injected as a Bier's block. Two hundred healthy women scheduled for ambulatory gynecological procedures were allocated to 1 of 2 groups in a randomized double-blind fashion. Group LIDO received lidocaine 2% 2 mL injected with a tourniquet 1 min before propofol 1% 2 mg/kg IV; group LCT/MCT received NaCl 0.9% 2 mL with tourniquet 1 min before propofol-LCT/MCT 1% 2 mg/kg IV. Spontaneous verbal expressions of pain, movement of hand, frowning, and moaning during the injection were recorded. The incidence and severity of pain were assessed 30 min and 6 h after surgery. Recall of pain was considered with a visual analog scale (VAS) score >1, and pain was graded as VAS 0-10. More women reported spontaneous verbal expression of pain with propofol-LCT/MCT (47% versus 24%; P = 0.0014; relative risk 1.61 [95% confidence interval, 1.22-2.13]). Among women with a painful injection, there was no difference after surgery regarding the intensity of pain or recall of pain. In contrast to previous reports, we found that propofol-LCT/MCT resulted in a more frequent incidence of pain than propofol 1% with IV lidocaine pretreatment. This may be due to the diversity of pain definitions used in studies or to the lack of premedication in our study.     

Antibiotic prophylaxis in pulmonary surgery: a double-blind study of penicillin versus placebo.

A prospective, randomized double-blind study comparing high-dose short-term penicillin-G prophylaxis with placebo was conducted on patients referred for elective pulmonary surgery. The major advantages of penicillin prophylaxis over placebo were observed for wound infections (2/45 vs 9/47, respectively, p = 0.03), postoperative antibiotic use (13/45 vs 23/47, respectively, p = 0.049), and postoperative hospital stay (median 10 days vs 13 days, respectively, p = 0.02). The prophylactic penicillin regimen had no effect on the incidence of empyema or lower respiratory tract infections. Staphylococcus aureus and Haemophilus were identified as the major pathogens in post-operative infections. Penicillin significantly reduced the incidence of S. aureus in spite of resistance to penicillin in most isolated strains, while the frequency of Haemophilus was similar in the two treatment groups. Colonization with Enterobacteriaceae and Pseudomonas aeruginosa was pronounced in the penicillin group. Few side-effects of penicillin treatment were recorded. Short-term penicillin prophylaxis is recommended, but the ideal prophylactic regimen in pulmonary surgery has not yet been found.     

Inhalation induction with sevoflurane: a double-blind comparison with propofol

We conducted a randomized, double-blind comparison of 8% sevoflurane and propofol as induction agents for day-case cystoscopy in 102 patients. All patients received an i.v. cannula and breathed oxygen 5 litre min-1. Anaesthesia was induced with propofol i.v. or inhalation of 8% sevoflurane and 10% Intralipid (as a placebo) i.v., delivered by a blinded observer. Anaesthesia was maintained in all patients with 2% sevoflurane via a face mask. Induction of anaesthesia with sevoflurane was significantly slower compared with propofol (mean 84 (SD 24) s vs 57 (11) s), but was associated with a lower incidence of apnoea (16% vs 65%) and a shorter time to establish spontaneous ventilation (94 (34) s vs 126 (79) s). Induction complications were uncommon in each group but the transition to maintenance was smoother with sevoflurane and was associated with less hypotension compared with propofol. Emergence from anaesthesia induced with sevoflurane occurred significantly earlier compared with propofol (5.2 (2.2) min vs 7.0 (3.2) min) and anaesthetic induction was also significantly cheaper with sevoflurane. According to a postoperative questionnaire, the majority of patients found both anaesthetic techniques acceptable. Nevertheless, significnatly more patients (14%) rated induction with sevoflurane as unpleasant compared with propofol (0) and significantly more patients (24%) would not choose sevoflurane induction compared with propofol (6%). This phenomenon may have been related to the particular patient population studied, however. Inhalation induction with 8% sevoflurane would appear to offer several objective advantages compared with induction with propofol in day-case patients, although a significant minority may dislike this technique.      

Safety and efficacy study with various doses of SS-cream in patients with premature ejaculation in a double-blind, randomized, placebo controlled clinical study.

OBJECTIVES: SS-cream is a topical agent made from the extracts of natural products for treating premature ejaculation (PE). To determine the optimal clinical dosage of SS-cream on PE, we investigated the safety and efficacy of SS-cream with various doses. A double blind, randomized placebo controlled clinical study was performed. METHODS: Fifty patients completed the study. Mean age of the patients was 37.1+/-1.O y and mean ejaculatory latency was 1.35+/-0.07 min. Sexual satisfaction rate of both the partner and patient was 16.2%. Each patient was instructed to apply the different cream (placebo, SS-cream 0.05, 0.10, 0.15, 0.20 g) on glans penis 1 h before sexual intercourse in random fashion. The ejaculatory latency was measured by stop watch and the satisfaction rate of both partner and patient was also recorded two times in the screening period and after the application of each test drugs. Clinical efficacy was considered if ejaculatory latency was prolonged more than 2 min and sexual satisfaction rate increased more than 20% than that of pretest values. RESULTS: The mean ejaculatory latencies were significantly prolonged after using various test drugs (placebo 2.27+/-0.32, SS-cream 0.05 g 4.47+/-0.81, 0.10 g 5.34+/-0.79, 0.15 g 6.22+/-0.87, 0.20 g 11.06+/-1.17 min, respectively). Clinical efficacies evaluated by ejaculatory latency were placebo 18%, SS-cream 0.05 g 30%, 0.10 g 60%, 0.15 g 54%, 0.20 g 84%, respectively. The satisfaction rate was also significantly increased dose-dependently (placebo 26%, SS-cream 0.05 g 60%, 0.10 g 70%, 0.15 g 78%, 0.20 g 90%, respectively). A side effect such as local mild burning sensation was noted in 35/250 times (14%) and no adverse effect on sexual function and no systemic side effects were observed. From the result of logistic regression analysis on clinical efficacy, the ED50 of SS-cream was obtained as 0.10 g. SS-cream 0.20 g was effective in 84% without any serious systemic side effects. CONCLUSION: From the above results, our conclusions are that SS-cream is effective on the treatment of PE with a few local side effects and that clinical optimal dose of SS-cream is 0.20 g.