Continuous epidural analgesia with bupivacaine-fentanyl versus patient-controlled analgesia with i.v. morphine for postoperative pain relief after knee ligament surgery

BACKGROUND: Both epidural analgesia and intravenous patient-controlled analgesia (PCA) have been found efficacious after various types of surgery. We compared the efficacy, safety, side effects and patient satisfaction of these methods in a randomized double-blind fashion after elective anterior cruciate ligament reconstruction of the knee. METHODS: Fifty-six patients had an epidural catheter placed at the L2-L3 interspace. Spinal anaesthesia with 15 mg of plain bupivacaine 5 mg/ml was performed at the L3-L4 interspace. After surgery the patients were randomly divided into three groups: 19 received a continuous epidural infusion with bupivacaine 1 mg/ml and fentanyl 10 mg/ml (F10), 19 patients received bupivacaine 1 mg/ml and fentanyl 5 microg/ml (F5) and 18 patients received saline (S). The rate of the epidural infusions was 0.1 ml kg(-1) h(-1). Each patient could also use an intravenous (i.v.) PCA device with 40 microg/kg bolus doses of morphine with a lockout period of 10 min and a maximum dose 240 microg kg(-1) h(-1). At the end of surgery ketoprofen 100 mg i.v. was given and continued orally three times a day. Patients were assessed for pain with a visual analogue scale (VAS) at rest and during activity, side effects and satisfaction at 3, 9 and 20 h. RESULTS: Both epidural infusions (F10, F5) provided better analgesia than epidural saline plus i.v. PCA (S) (P<0.05). There was slightly less nausea in the S group (NS). In spite of the difference in the quality of pain relief, there was no difference between the groups in patient satisfaction regarding analgesic therapy. CONCLUSION: Epidural infusion of fentanyl (1 microg kg(-1) h(-1) or 0.5 microg kg(-1) h(-1)) and bupivacaine (0.1 mg kg(-1) h(-1)) provided better pain relief but more side effects than intravenous morphine patient-controlled analgesia after knee ligament surgery. Almost all patients in all groups were satisfied with their pain relief.     

Efficacy of salbutamol via Easyhaler unaffected by low inspiratory flow

The fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30-60 l min(-1). The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 microg) delivered via Easyhaler at a target inspiratory flow of 30 l min(-1) with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer. This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min(-1), and the actual PIFR through Easyhaler was recorded. The average PIFR through Easyhaler was 28.7 l min(-1). The difference in the maximum value of FEV1 (FEV1max) between the treatments after drug inhalation was 0.01 l. The mean of FEV1max was 2.67 l after pMDI plus spacer compared to 2.69 l after Easyhaler. Improvements in FEV1 were clinically significant. No significant differences between treatments were found. A reasonably low inspiratory flow rate through Easyhaler produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly.     

The effect of ATP on the ciliary activity of normal and pathological human respiratory mucosa in vitro

The effect of adenosine triphosphate (ATP) on the airway ciliary beating frequency (CBF) of mucosal explants excised from human maxillary sinuses was studied by measuring CBF photoelectrically before and after immersion of the explants in a solution containing ATP. In samples from 64 patients with chronic sinusitis the CBF was not significantly different from the CBF in mucosal specimens from healthy tissue of 22 patients without infection. During 15 min immersion, ATP (1 mg/ml) slightly (by 5%, p less than 0.05 in healthy tissue; by 2.7%, p less than 0.01, in tissue from sinusitis patients) increased the CBF. The effect of 10 mg/ml concentration was more pronounced (19.6%). It is concluded that the impairment in ciliary function caused by chronic sinusitis is reversible when the mucosal endothelium is cleansed of the infected mucus, and that the ciliostimulatory action of ATP seen in animals is also present in human respiratory mucosa.     

Patient-controlled epidural analgesia versus continuous epidural analgesia after total knee arthroplasty

BACKGROUND: Patient-controlled epidural analgesia (PCEA) has been found to be an effective method for pain relief during labour and after surgery. The goal of this study was to compare the efficacy of bupivacaine-fentanyl PCEA and continuous epidural infusion with the same mixture for treatment of pain after total knee arthroplasty. METHODS: Fifty-four patients under spinal anaesthesia were allocated to two groups in this randomized, double-blind study: the PCEA group could demand a bolus of 0.05 ml/kg of the bupivacaine 1.1 mg/ml and fentanyl 5 microg/ml solution, with a lockout interval of 10 min and total dose limit of three bolus doses per hour. The EPI group received a continuous infusion of 0.1 ml kg(-1) h(-1) of the same bupivacaine-fentanyl solution, and only a minimal extra bolus dose of 0.2 ml with the same lockout interval. All the patients received also paracetamol 1 g, orally, three times a day. In addition to pain scores at rest and during leg lifting, the 20-h analgesic consumption and the incidence of side effects were recorded. RESULTS: Forty-nine patients completed the study. The bupivacaine and fentanyl consumption during 20 h was smaller in the PCEA group (P<0.001). Analgesia and the need for rescue-opioid medication were similar in both groups. There were no differences between the PCEA and EPI groups regarding the incidence of side effects. Five patients were confused about how to operate the PCEA apparatus. CONCLUSION: The amount of bupivacaine-fentanyl solution consumed was significantly less with PCEA than with continuous infusion of bupivacaine-fentanyl solution without affecting the quality of postoperative analgesia after total knee arthroplasty. Several of the elderly patients had difficulties in operating the PCEA apparatus.     

Safety of formoterol after cumulative dosing via Easyhaler and Aerolizer

This randomised, double-blind, double-dummy, cumulative dose, multicentre crossover study aimed to demonstrate non-inferiority in safety of formoterol delivered via Easyhaler versus Aerolizer. The secondary objective was to compare the efficacy of the devices. Thirty-three adult asthmatic subjects entered the study and 32 completed it. The study comprised screening and two study days, with each subject inhaling 96 microg (12, 12, 24 and 48 microg) cumulative dose of formoterol via the study inhalers. Serum potassium (S-K+), vital signs and spirometry were performed at baseline, 1h after each dose and additionally 4h after the last dose. The primary safety variable was S-K+. Secondary safety variables were heart rate, corrected QT interval, blood pressure, serum glucose and adverse events. Spirometry was assessed to evaluate efficacy. The results showed non-inferiority in safety of formoterol inhaled via Easyhaler compared to Aerolizer. The adjusted treatment difference in the S-K+ values after 96 microg cumulative dose of formoterol was 0.14 mmol/L being clearly above the pre-determined lower limit of the non-inferiority criterion of -0.2 mmol/L. There were dose-related changes in secondary efficacy variables after both treatments. The changes were comparable in most of the parameters but heart rate was statistically significantly higher and decrease in diastolic blood pressure greater after formoterol via Aerolizer than that via Easyhaler. The occurrence of adverse events was dose-related, the most common events being tremor, hypokalaemia, headache and palpitation. The spirometry results showed no statistically significant difference in efficacy between the treatments. In conclusion, formoterol delivered via Easyhaler was as safe as via Aerolizer.     

The effect of intravenous dopamine and dobutamine on blood circulation during a microvascular TRAM flap operation

A study was conducted to assess the effect of intraoperatively administered inotropic agents on blood flow in the recipient and donor vessels, during breast reconstruction with a muscle sparing free TRAM flap. Twenty-one consecutive patients were randomized into 3 groups receiving either dopamine, dobutamine, or placebo. When the flap and all vessels had been fully dissected but not yet divided, the study drug was administered intravenously for 15 minutes. Hemodynamic parameters and transit-time flow of the thoracodorsal and inferior epigastric arteries were monitored.Both dobutamine and dopamine infusions resulted in significant raises in cardiac output and mean arterial pressure. However, while dobutamine resulted in a higher cardiac output (P = 0.001) and a decrease in systemic vascular resistance (P = 0.028), the increase in mean arterial pressure was greater with dopamine (P = 0.002). Only the dobutamine group showed increased blood flow, in both the thoracodorsal (P = 0.043) and the inferior epigastric (P = 0.043) arteries.If vasoactive agents are needed during microvascular anesthesia, dobutamine seems to be more advantageous than dopamine.     

Lack of effect of hepatic enzyme induction on metabolic control in patients with type 2 (non-insulin-dependent) diabetes

A placebo-controlled, double-blind crossover study was carried out in 11 non-insulin-dependent (type 2) diabetic patients to find out the effects of a hepatic enzyme inducer (phenobarbital, 100 mg/day for 2 months) on the metabolic control, plasma C-peptide, insulin, serum, and lipoprotein lipid levels. Phenobarbital induced a significant increase in hepatic antipyrine metabolizing activity, but no significant changes were found in fasting or postload blood glucose, plasma C-peptide, or insulin levels during the study. There was a significant increase in serum total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, as well as in serum total and very low-density lipoprotein triglycerides, during phenobarbital treatment as compared with placebo.     

Pulmonary Deposition and Clinical Response of99mTc-Labelled Salbutamol Delivered from a Novel Multiple Dose Powder Inhaler

Pulmonary deposition of ^99mTc-labelled sulbutamol was determined after delivery from a novel multiple dose powder inhaler (Easyhaler^®). The clinical efficacy of the inhalation powder, evaluated simultaneously with gamma camera detection, was compared with that obtained after drug delivery from a metered dose inhaler-spacer combination. The study was performed as an open, non-randomized cross-over trial. A single dose of radiolabelled inhalation powder was inhaled on the first and the inhalation aerosol, as control, on the second study day. Sulbutamol sulphate was labelled with ^99mtechnetium, and the inhalation powder was formulated by mixing radioactive drug particles with carrier material. Aerodynamic properties of the radiolabelled inhalation powder were similar to those of the unlabelled salbutamol powder. Delivered dose from the breath-actuated powder inhaler was adjusted to be equal to two puffs from a conventional aerosol actuator with a short plastic mouthpiece. Twelve non-smoking asthmatic patients participated in the trial. The mean pulmonary deposition of 24% was obtained after drug delivery from Easyhaler^® powder inhaler. Clinical efficacy of the medications was similar in terms of area under the FEV₁ curve, maximum FEV₁ and the improvement ratio. Thus it can be suggested that powder delivery from Easyhaler^® powder inhaler and the aerosol delivery through the spacer are equally effective.     

Guar gum and gemfibrozil--an effective combination in the treatment of hypercholesterolaemia

Twenty-nine hypercholesterolaemic patients, treated for one year with gemfibrozil but being still hypercholesterolaemic (serum total cholesterol greater than or equal to 6.25 mmol/l) were included in a double-blind trial to evaluate the hypocholesterolaemic effects of gemfibrozil-guar gum combination (GE + GU) vs. gemfibrozil-placebo combination (GE + PL) using a cross-over study design. The patients were treated with gemfibrozil on a constant dosage (range 900-1200 mg/day) during the entire trial. After a 4-week run-in period on GE + PL treatment the patients were randomly allocated to 2 groups: one received GE + GU 15 g/day, and the other GE + PL for 3 months and after that groups were crossed over. Guar gum and placebo were administered as granules taken 3 times a day during meals. Serum total cholesterol was 8.61 +/- 0.17 mmol/l before gemfibrozil therapy, and 7.29 +/- 0.15 mmol/l at the end of the run-in period on GE + PL (P less than 0.01). During the double-blind phase serum total cholesterol values were 6.28 +/- 0.19 mmol/l at the end of the GE + GU treatment period and 7.21 +/- 0.16 mmol/l at the end of the GE + PL treatment period (P less than 0.01). At the end of the GE + GU treatment period serum total cholesterol was 27% lower and LDL-cholesterol 39% lower than before gemfibrozil treatment. A marked improvement (23%) was found in HDL/LDL ratio during GE + GU treatment compared with GE + PL treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long term treatment of severe hypercholesterolaemia with guar gum

The long term efficacy of granulated guar gum, 15-30 g per day, was studied in 23 patients with severe hypercholesterolaemia (serum cholesterol concentration between 8.0 and 14.3 mmol/l). Originally, 29 patients participated in the study. Two patients dropped out because of gastrointestinal side effects, two others were not willing to complete the study without any given reason, and two discontinued the study because of hospitalization. A 1-month placebo period preceded the guar gum treatment, and another 1-month placebo period followed after 50 weeks of active treatment. The serum total cholesterol concentration (mean +/- SEM) was reduced from 10.0 +/- 0.4 mmol/l to 8.2 +/- 0.3 mmol/l (P less than 0.001) after 8 weeks and to 9.0 +/- 0.4 mmol/l (P less than 0.001) after 50 weeks on guar gum. During the second placebo period serum cholesterol returned to the pretreatment level. After 34 weeks of active treatment the serum LDL-cholesterol concentration had fallen by 15% and that of apoprotein B by 14% from the baseline. The changes in lipid and lipoprotein levels were independent of the initial values and the type of hypercholesterolaemia. Serum triglycerides, HDL-cholesterol, body weight and blood pressure showed no significant changes during the trial. Of the study subjects, 20 reached the maximum intended dose of 30 g per day guar gum between 8 and 14 weeks and thereafter 11 subjects continued the dose of 30 g/day while 12 subjects reduced the dose to 15-25 g/day.(ABSTRACT TRUNCATED AT 250 WORDS)