Sensory Assessment and Regression Rate of Bilateral Oblique Subcostal Transversus Abdominis Plane Block in Volunteers.

BACKGROUND AND OBJECTIVES: The analgesic effect and duration of a transversus abdominis plane (TAP) block remain controversial. Transversus abdominis plane blocks are effective for somatic/incisional pain but do not provide analgesia for visceral pain from intra-abdominal procedures. The purpose of this study was to assess the area and extent of cutaneous sensory blockade and the regression of dermatomal anesthesia after bilateral oblique subcostal TAP block. METHODS: This observational, prospective clinical study consisted of 12 healthy volunteers. All volunteers received a bilateral oblique subcostal TAP block under real-time ultrasound guidance with 20 mL of 0.375% ropivacaine. The anterior abdominal cutaneous area was divided into 3 parts (midabdomen, left-lateral abdomen, right-lateral abdomen) using 2 lines drawn in a parasagittal fashion 5 cm lateral to the midline. The area of cutaneous sensory blockade involving the anterior abdomen was assessed 30 minutes after institution of the block using a cold stimulus. This was followed by repeated measurements using a cold stimulus applied along parasagittal lines drawn 3 cm lateral to the midline at 0.5, 6, 10, 14, 18, 22, and 26 hours after blockade. RESULTS: The area of cutaneous sensory blockade of the abdomen was 332 (SD, 73) cm; that of the midabdomen was 253 (SD, 29) cm, which represented an average of 90% of the area of the midabdomen; and that of the lateral abdominal wall (combination of left-lateral abdomen and right-lateral abdomen) was 79 (SD, 62) cm, which represented an average of 26% of total lateral abdominal area. Dermatomes T7-T12 of the midabdomen were successfully blocked in all volunteers after using the bilateral oblique subcostal technique. However, T6 and L1 were only variably blocked. The area of cutaneous sensory block of the anterior abdomen regressed over the ensuing 22 hours in the following manner: 90%, 87%, 73%, 50%, 22%, 3%, and 0% at 0.5, 6, 10, 14, 18, 22, and 26 hours, respectively. CONCLUSIONS: Bilateral oblique subcostal TAP block produces a widespread cutaneous sensory blockade with a consistent dermatomal distribution in the midabdomen for a considerable effective duration.

The fixed combination efficacy assessment in patients with secondary neovascular glaucoma and diabetes mellitus.

PURPOSE: To assess IOP-lowering efficacy of bimatoprost/timolol fixed combination (Ganfort®) in patients with diabetes mellitus (DM) and uncontrolled secondary neovascular glaucoma (NG). MATERIALS AND METHODS: Fifty patients (51 eyes) with uncontrolled secondary neovascular glaucoma and diabetes mellitus were enrolled in the study. All patients with an uncontrolled IOP have been proposed to switch current IOP-lowering therapy to Ganfort®. In case target IOP level was not reached filtration surgery was recommended. Ganfort® administration - once a day in the morning. RESULTS: IOP-lowering has been observed in all patients when switched to Ganfort®. Mean IOP level was almost 3-x lower versus baseline in 72.5% of patients (37 eyes). The patients achieved target IOP of 15-17 mmHg. As a result, no surgical intervention was required. Significant IOP-lowering has been observed in another group of patients (14 eyes, 27.5 %) nevertheless due to glaucoma progression, these patients are still subjected to surgical treatment. CONCLUSION: IOP-lowering fixed combination Ganfort® (Allergan) can be used in patients with secondary neovascular glaucoma and diabetes mellitus as a drug of choice to control the IOP level. Even in cases when target IOP is not achieved, Ganfort® can be administered in pre-operative period and helps to reduce postoperative complications.

Computer-aided (in silico) approaches in the mode-of-action analysis and safety assessment of ostarine and 4-methylamphetamine.

OBJECTIVE: This study exemplifies computer-aided (in silico) approaches in assessing the risks of new psychoactive substances emerging in the European Union. In this work, we (i) consider the potential of Ostarine exhibiting psychoactivity and (ii) anticipate potential activities and toxicities of 4-methylamphetamine. METHOD: The approach, termed in silico target prediction, suggests potential protein targets modulated by compounds given their chemical structure. This is achieved by first establishing the associations between chemical structure and protein targets using data from the bioactivity database, ChEMBL, via the use of two different computational algorithms. On the basis of the associations, protein targets and consequently the mode of action of novel compounds were predicted. RESULTS: For Ostarine, none of the targets anticipated are currently known to elicit psychoactivity. Furthermore, Ostarine is unlikely to cross the blood-brain barrier to reach relevant target sites on the basis of its physicochemical properties. For 4-methylamphetamine, toxicities were anticipated, that is, serotonin syndrome (based on the prediction of SERT) and other effects similar to related substances, that is, methamphetamine. CONCLUSION: From the two case studies, we showed that in silico target prediction appears to have potential in assessing new psychoactive compounds where experimental data are scarce. The applicability domain of target predictions when applied to psychoactive compounds needs to be established in future work.

Safety and efficacy of aliskiren in the treatment of hypertension: a systematic overview.

INTRODUCTION: Aliskiren is the first orally active direct renin inhibitor approved for the treatment of hypertension. Aliskiren's inhibitory effect on angiotensin I generation, through renin blockade, is highly specific and long-lasting (24 hours). This feature differentiates aliskiren from traditional antihypertensive drugs. AREAS COVERED: This paper reviews the results of various clinical trials which investigate the safety and efficacy of aliskiren on blood pressure (BP) reduction and clinical end points. EXPERT OPINION: Aliskiren is suitable for once-daily administration. Its antihypertensive effect is comparable or superior to that of other antihypertensive agents at recommended doses. The tolerability profile of aliskiren is placebo-like at the licensed doses of 150 and 300 mg. In particular, the discontinuation of therapy due to clinical adverse events occurs similarly among patients treated with either aliskiren or placebo. Aliskiren is not recommended in association with ACE-inhibitors or angiotensin II receptor blockers in patients with type 2 diabetes and renal impairment. Pending disclosure of full results, the early termination of the ALTITUDE seems to confirm previous concerns about the safety of the dual pharmacological blockade of the renin-angiotensin system in these patients. Aliskiren is a well-tolerated antihypertensive drug that may help to achieve the recommended targets of BP control.

[Ultrasonographic assessment of hemidiaphragm paralysis secondary to interscalene block]. / Evaluación ultrasonográfica de la parálisis hemidiafragmática secundaria a bloqueo interescalénico.

BACKGROUND: In shoulder surgery, interscalene brachial plexus block has an incidence of 100% hemidiaphragm palsy due to phrenic nerve block. Controling the hemidiaphragm becomes a security ventilation parameter. OBJECTIVE: identify and evaluate with ultrasound hemidiaphragm paralysis after interscalene block. METHODS: This prospective study included 50 patients scheduled for shoulder surgery with interscalene block using neurostimulation. Diaphragmatic movement was evaluated by ultrasound prior to placement of block and the end of the surgical procedure to make the comparison between the two measurements. RESULTS: Comparing the duration of the respiratory cycle at the start and the end of the surgical procedure, both normal and forced ventilation, there is a statistically significant difference of p < 0.001, as with the depth of the hemidiaphragm was found p < 0.001. 90% of patients had no adverse events, 8% had Horner's syndrome and 2% periauricular hypoesthesia. Hemidiaphragm paralysis was found in all cases, with a volume of 30 mL local anesthetic. CONCLUSIONS: Ultrasound is a reliable tool that allows real time viewing of the respiratory cycle and measurements of the diaphragm dome it serves to identify diaphragmatic hemiparesis.

Interscalene block for shoulder surgery in physician-owned community ambulatory surgery centers.

PURPOSE: To retrospectively report on a series of patients who had interscalene block regional anesthesia performed for outpatient open and arthroscopic shoulder surgical procedures in a community-based ambulatory surgery center setting. METHODS: We reviewed the cases of 1,945 patients who had interscalene block regional anesthesia performed during an 8-year period. RESULTS: The complication rate was 0.63%, with all complications occurring in the immediate postoperative period, none of which were permanent. CONCLUSIONS: With an expert, experienced anesthesia team, the interscalene block can be a safe method (temporary complication rate, 0.63%) of intraoperative anesthesia and perioperative analgesia for outpatient open and arthroscopic shoulder surgery in physician-owned ambulatory surgery centers. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Focused review: ropivacaine versus bupivacaine for epidural labor analgesia.

Neuraxial analgesia is frequently administered to women in labor. For many years, bupivacaine has been used because of its long duration of action, lack of excessive motor block, and minimal fetal and neonatal effects. However, bupivacaine is one of the most cardiotoxic local anesthetics in current use and motor block is still a problem. Many local anesthetics such as bupivacaine exist in 2 forms, levorotatory and dextrorotatory. Ropivacaine, an amide local anesthetic produced in the pure levorotatory form addresses some of the concerns related to bupivacaine. In this article, we present the literature comparing ropivacaine and bupivacaine to determine whether there is an advantage to using one of these local anesthetics for labor analgesia. We found that there is no advantage to the routine use of ropivacaine for labor analgesia.

Hyperemia-associated costs of medication changes in glaucoma patients treated initially with prostaglandin analogs.

AIMS: To develop a model to estimate and compare the cost of changing therapy due to hyperemia in glaucoma patients treated initially either with latanoprost, bimatoprost, or travoprost monotherapy. METHODS: Data collected from the HealthCore Integrated Research Database, as part of the Glaucoma Adherence and Persistency Study (GAPS), were used to populate the model. Patients with a documented diagnosis of glaucoma who were newly treated (no ocular hypotensive medication and no glaucoma-related procedure during 6 months before first prescription) with latanoprost, bimatoprost, or travoprost monotherapy were identified. The time horizon for the base-case model was the duration of chart abstraction (mean = 4.1 years); a 3-month model also was developed. Physician-reported rates of hyperemia were obtained from chart reviews of 300 patients. Transition rates reflected events related to reports of hyperemia where a physician-driven change (switch or discontinuation) in therapy was documented. The per-patient direct cost (2008) due to hyperemia-driven change in therapy was calculated as the sum of the cost of the initial prescription plus the cost of the office visit where the patient was evaluated and the decision to change therapy was made. Costs were stratified by whether patients were hyperemia free or discontinued the initial therapy due to hyperemia. RESULTS: From the sample of 13,977 newly treated patients, 8,743 patients were started on a prostaglandin monotherapy only. Of these, 5,726 received latanoprost, 1,633 were treated with bimatoprost, and 1,384 received travoprost index monotherapy. Across all treatment groups, costs among hyperemia-free patients were US$73.67 versus US$140.02 for those who discontinued the initial prostaglandin due to hyperemia. Per-patient costs were lowest in the group treated initially with latanoprost. For the base-case model, with latanoprost as the reference, total per-patient incremental costs due to hyperemia-driven change in therapy were US$5.92 for bimatoprost and US$5.43 for travoprost. Results were not highly sensitive to increases either in the incidence of hyperemia among latanoprost-treated patients or in the cost of latanoprost. CONCLUSIONS: Hyperemia results in increased overall costs in patients treated with latanoprost, bimatoprost, and travoprost. Treatment with latanoprost is associated with lower hyperemia-related costs than treatment with bimatoprost or travoprost.

Bimatoprost/timolol: a review of its use in glaucoma and ocular hypertension.

Topically administered bimatoprost 0.03%/timolol 0.5% ophthalmic solution (bimatoprost/timolol: Ganfort) comprises the synthetic prostamide bimatoprost (structurally related to prostaglandin F2 alpha) and the beta-adrenergic receptor antagonist timolol. Bimatoprost/timolol (one drop administered in the affected eye[s] once daily in the morning or evening) is an effective and well tolerated fixed combination for lowering intra-ocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (OHT), including individuals uncontrolled on monotherapy with a beta-adrenergic receptor antagonist or prostaglandin analogue/prostamide.

Taranabant, a novel cannabinoid type 1 receptor inverse agonist.

Merck & Co Inc is developing the cannabinoid receptor type 1 inverse agonist taranabant for the potential treatment of obesity and nicotine dependence. By October 2006, the drug had entered phase III trials for obesity, and by May 2008, a phase II study of taranabant as an aid to smoking cessation in chronic cigarette smokers had been completed.

A 6-month assessment of bimatoprost 0.03% vs timolol maleate 0.5%: hypotensive efficacy, macular thickness and flare in ocular-hypertensive and glaucoma patients.

AIM: To compare 6 months of treatment with bimatoprost and timolol in terms of their hypotensive efficacy and secondary effects, including changes in macular thickness and the inflammatory reaction induced in the anterior chamber. METHODS: A prospective, randomized, parallel-group trial performed on 30 eyes of 30 patients per group. The main outcome measure was the difference between the IOP value taken between the baseline visit and the 6-month-visit. Macular thickness determined through optical coherence tomography and anterior chamber inflammation estimated using the laser flare meter was also evaluated. Adverse events were recorded during the study period. RESULTS: Bimatoprost treatment gave rise to a significantly lower mean IOP than timolol in all follow-up visits as from the first month (P<0.05). Bimatoprost achieved high percentage IOP reductions from baseline in a significantly higher proportion of patients (P<0.05). Macular thickness and anterior chamber flare failed to vary significantly both between the two groups and within each group during the 6-month evaluation (P>0.05). CONCLUSIONS: Bimatoprost 0.03% once daily showed a greater efficacy then timolol 0.05% twice daily in patients with elevated IOP. No significant differences were detected in macular thickness or anterior uveitis using optical coherence tomography and laser flare photometry.

An economic evaluation of bupivacaine plus fentanyl versus ropivacaine alone for patient-controlled epidural analgesia after total-knee replacement procedure: a double-blinded randomized study.

BACKGROUND AND OBJECTIVES: Total-knee replacement (TKR) surgery is one of the most painful orthopedic procedures after surgery. Opioid has been commonly combined with a local anesthetic to improve the quality of pain relief, but the treatment has opioid-related side effects. This study compared the cost effectiveness of patient-controlled epidural analgesia (PCEA) with 0.0625% bupivacaine plus fentanyl (BF) 3 microg/mL versus 0.15% ropivacaine alone (R) during the first 48 hours after TKR procedure. METHODS: This prospective randomized double-blinded study was performed on 70 patients who underwent unilateral TKR procedure and received either BF or R after surgery. Visual analog scale (VAS) pain score at rest and upon movement, side effects, and cost of treatment were compared. RESULTS: Overall pain at rest and upon movement between groups was not significantly different (P = 0.58, 95% CI = 4.4 to -7.8 and P = 0.8, 95% CI = 6.4 to -8.2, respectively). Patients in the BF group experienced more pruritus and had more vomiting episodes than those in the R group (P = .015), whereas no difference occurred in other side effects. Nevertheless, patient satisfaction with pain management was higher in the BF group compared with that in the R group. In addition, pain treatment with bupivacaine and fentanyl was 18% less costly compared with ropivacaine alone. CONCLUSIONS: Considering the economic evaluation, we conclude that PCEA with 0.0625% bupivacaine plus fentanyl 3 microg/mL is more cost effective and provides more patient satisfaction than PCEA with ropivacaine alone. However, use of epidural ropivacaine alone causes fewer opioid-related side effects, particularly pruritus and vomiting.

Benefit-risk assessment of ropivacaine in the management of postoperative pain.

Ropivacaine is a long-acting amide-type local anaesthetic, released for clinical use in 1996. In comparison with bupivacaine, ropivacaine is equally effective for subcutaneous infiltration, epidural and peripheral nerve block for surgery, obstetric procedures and postoperative analgesia. Nevertheless, ropivacaine differs from bupivacaine in several aspects: firstly, it is marketed as a pure S(-)-enantiomer and not as a racemate, and secondly, its lipid solubility is markedly lower. These features have been suggested to significantly improve the safety profile of ropivacaine, and indeed, numerous studies have shown that ropivacaine has less cardiovascular and CNS toxicity than racemic bupivacaine in healthy volunteers. Extensive clinical data have demonstrated that epidural 0.2% ropivacaine is nearly identical to 0.2% bupivacaine with regard to onset, quality and duration of sensory blockade for initiation and maintenance of labour analgesia. Ropivacaine also provides effective pain relief after abdominal or orthopaedic surgery, especially when given in conjunction with opioids or other adjuvants. Nevertheless, epidurally administered ropivacaine causes significantly less motor blockade at low concentrations. Whether the greater degree of blockade of nerve fibres involved in pain transmission (Adelta- and C-fibres) than of those controlling motor function (Aalpha- and Abeta-fibres) is due to a lower relative potency compared with bupivacaine or whether other physicochemical properties or stereoselectivity are involved, is still a matter of intense debate. Recommended epidural doses for postoperative or labour pain are 20-40 mg as bolus with 20-30 mg as top-up dose, with an interval of >or=30 minutes. Alternatively, 0.2% ropivacaine can be given as continuous epidural infusion at a rate of 6-14 mL/h (lumbar route) or 4-10 mL/h (thoracic route). Preoperative or postoperative subcutaneous wound infiltration, during cholecystectomy or inguinal hernia repair, with ropivacaine 100-175 mg has been shown to be more effective than placebo and as effective as bupivacaine in reducing wound pain, whereby the vasoconstrictive potency of ropivacaine may be involved. Similar results were found in peripheral blockades on upper and lower limbs. Ropivacaine shows an identical efficacy and potency to that of bupivacaine, with similar analgesic duration over hours using single shot or continuous catheter techniques. In summary, ropivacaine, a newer long-acting local anaesthetic, has an efficacy generally similar to that of the same dose of bupivacaine with regard to postoperative pain relief, but causes less motor blockade and stronger vasoconstriction at low concentrations. Despite a significantly better safety profile of the pure S(-)-isomer of ropivacaine, the increased cost of ropivacaine may presently limit its clinical utility in postoperative pain therapy.

New local anesthetics. Are they worth the cost?

Epidural analgesia that uses dilute concentrations of bupivacaine with fentanyl or sufentanil provides excellent analgesia, good sensory-motor discrimination, and minimal toxicity and is inexpensive. The new local anesthetic agents, ropivacaine and levobupivacaine, offer potential improvements in the risk of toxicity when administered in large doses but probably no important clinical difference when used in dilute concentrations for labor analgesia. After accounting for the potency difference, ropivacaine offers little or no motor-sparing advantage over bupivacaine. Currently, epidural anesthesia with concentrated bupivacaine is rarely used for cesarean section, so there is little indication for the newer anesthetic agents in this setting either. The authors believe that large difference in cost cannot be justified on the basis of currently available data.

[Use of ropivacaine for peridural postoperative analgesia]. / Utilisation de la ropivacaïne par voie péridurale pour l'analgésie postopératoire.

OBJECTIVES: To describe pharmacology and toxicology of ropivacaine. To assess the clinical efficacy of ropivacaine when used for postoperative epidural analgesia and to provide recommendations for clinical practice. DATA SOURCES: Search in the Medline data base of original articles in French and English published since 1995, using the following key words: ropivacaine, postoperative analgesia, epidural, caudal block. STUDY SELECTION: Prospective randomised studies in adults and children were selected. Letters to editors and editorials were excluded. DATA EXTRACTION: Articles have been analyzed: to determine the dose of ropivacaine required for postoperative epidural analgesia, to assess the benefits of combination of epidural ropivacaine and additives (opioids or other), to compare epidural ropivacaine and bupivacaine and to assess the use of ropivacaine via caudal route for paediatric postoperative analgesia. DATA SYNTHESIS: 20 mg h-1 of ropivacaine is required to provide effective analgesia. This dose produces a motor block in a significant number of patients. Combination with an opioid allows for a reduction in ropivacaine requirement and subsequently in the incidence of motor blockade. In adults, equipotency ratio of ropivacaine and bupivacaine varies between 1.5/1 and 1/1 depending upon the concentration used. At equipotent doses, early postoperative mobilisation is facilitated with ropivacaine. In case of paediatric caudal analgesia, this ratio is close to 1. CONCLUSIONS: Epidural ropivacaine combined with opioid provide good postoperative pain relief. Reduction in the incidence of motor blockade and safe toxicological profile make this local anaesthetic a suitable alternative of bupivacaine for postoperative epidural analgesia.