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Favipiravir (T-705) is a new antiviral drug with strong inhibitory activity on RNA-dependent RNA polymerase of most RNA virus genome. All the influenza viruses have been shown fully sensitive to this new antiviral, including genetic strains to neuraminidase inhibitors (oseltamivir) resistance. Its mechanism of action lies in blocking viral replication and induction of lethal mutagenesis which determines the loss of infective activity of influenza viruses. Its activity is particularly intense in the respiratory tract, decreasing the viral load to non-infectious levels. Clinical trials in humans have not yet completed but have very favourable results. It seems that the best therapy would be the combination of favipiravir with oseltamivir; both antivirals are synergistic and avoid the emergence of resistance.

Introduction: Dexmedetomidine prolongs sensory block of ropivacaine. Our objective was to study whether this extension would produce better postoperative pain control compared to that produced by clonidine in patients undergoing arthroscopic shoulder., Materials and Methods: Study comparative, longitudinal, controlled, randomized into 3 groups. Control group I: ropivacaine 0.75% clonidine group II: 0.75% ropivacaine plus clonidine 1mg/kg group iiidexmedetomidine: 0.75% ropivacaine more dexmedetomidine 1mg/kg. Interscalene block single dose ultrasound-guided. Sensory and motor blockade, pain intensity, sedation level, heart rate, respiratory rate, blood pressure at 6, 12 and 24hours was measured., Results: Pain intensity at 6hours in groups I and II moderate to severe pain, mild pain group iii. At 12hours the groups IIand II showed moderate to severe pain by more than 60% of patients, and in group iiionly 10%. At 24hours I and II group 20% of patients they continued to moderate pain., Conclusion: The prolonged interscalene block produced by dexmedetomidine provided better postoperative pain control during the first 24hours., (Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Stimulating catheters allow the catheter point to be positioned near the nerve, thus reducing the amount of local anaesthetic required for a successful block. There is currently a debate on what is the stimulation intensity required to provide adequate analgesia, although it does seem that if it is obtained with 1mAmp or less the block is more effective. The objective of the study was to demonstrate whether different neurostimulation intensities with the stimulating catheter at femoral nerve level, had an influence on the adequacy of post-surgical analgesia during the 48h after total knee arthroplasty., Material and Methods: A comparative, prospective and randomised study was conducted on patients subjected to total knee replacement. After surgery with subarachnoid anaesthesia, a continuous femoral block was performed with a stimulating catheter at a neurostimulation intensity 0.2 and 0.5mAmp in Group 1, between 0.6 and 1mAmp in Group 2, equal or higher than 1.1mAmp in Group 3, and in Group 4 the catheter was introduced between 3-5cm without looking for a motor response. A dose of 0.2% ropivacaine 0.4mL/kg and an infusion at 5mL/h, with boluses of 10mL/30min, was administered via the catheter. Sciatic nerve block was also performed on all patients with 20ml of 0.5% ropivacaine. The patient demographics were recorded, as well as, post-surgical analgesia details, sensory and motor block in each area, boluses requested, rescue analgesia, and undesirable effects at 8, 16, 24, 36 and 48h., Results: A total of 124 patients were included, 32 in Group 1 (25.8%), 21 in Group 2 (16.9%), 31 in Group 3 (25%), and 40 in group 4 (32.3%). The 4 groups were homogeneous as regards age, height, weight and ASA. There were no statistically significant differences found in the post-operative pain, except during movement in the femoral area at 36 hours (p=.032). There were also no statistically significant differences found in the sensory block in the femoral area at 48 hours (p=.019) and in the femoral cutaneous nerve block at 8 hours (p=.049) or at 24 hours (p=.045). As regards motor block, differences were only found in the obturator nerve at 24 hours (p=.016). There were no differences in rescue analgesia, patient controlled analgesia (PCA) boluses requested or administered, except that the number of boluses requested at 16 hours was less in Group 3 (p=.049). There were also no significant differences in undesirable effects or in the level of satisfaction of the patients between the four groups., Conclusions: In our study, no influence was found on the level of analgesia provided after knee replacement surgery with the neurostimulation intensity to which the neuromuscular system involved responded when a stimulating catheter is inserted at femoral level., (Copyright © 2011 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

Introduction: To compare the efficacy of a multimodal analgesia with 2 different techniques (femoral nerve block with a single dose and continuous femoral nerve block) in the control of pain, use of opioids, and secondary effects in patients subjected to total knee replacement., Material and Methods: A prospective randomised study of patients subjected to knee replacement with subarachnoid anaesthesia. The postoperative analgesia consisted of tramadol, dexketoprofen and paracetamol, and one of the following techniques: Femoral nerve block with a single dose of 30mL of 0.5% ropivacaine, or that dose plus a continuous infusion via a femoral catheter of 0.375% ropivacaine 6ml/h for 48h. The demographic, anaesthetic and surgical variables were recorded, along with the pain intensity using a visual analogue scale, opioid use, and complications at 24 and 48h after surgery., Results: A total of 104 patients were included. There no differences in the demographic data between the groups. The pain intensity was lower in the group that had continuous femoral block, particularly at 48h, compared to the single-dose block, and with a lower use of rescue analgesia in the continuous femoral block. The incidence in secondary effects was similar, with a lower long-term sensory block being observed in the femoral block with a single dose., Conclusions: The use of peripheral nerve block is accepted practice for analgesia after knee replacement surgery. Continuous femoral block is a valid alternative, decreasing the use of rescue opiates and pain intensity (particularly at 48h) compared to isolated femoral block., (Copyright © 2011 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

Background and Objectives: The interscalene is one of the most common approaches used in brachial plexus block. However, the association of this approach with the ipsilateral blockade of the phrenic nerve has been demonstrated. The resulting diaphragmatic dysfunction causes changes in lung mechanics, which can be potentially deleterious in patients with limited respiratory reserve. The objective of the present study was to evaluate the repercussion of interscalene brachial plexus block on pulmonary function by measuring forced vital capacity (FVC)., Methods: This is a double-blind study with 30 patients, physical status ASA I or II, randomly separated into two groups of 15 patients each; 0.5% ropivacaine (Ropi Group) or 0.5% bupivacaine with epinephrine (Bupi Group) was administered. A peripheral nerve stimulator was used, and 30 mL of the local anesthetic were administered. Four spirometries were done in each patient: before the blockade, 30 minutes, four hours, and six hours after the blockade. Patients were not sedated., Results: One patient in the Ropi Group and three patients in the Bupi Group were excluded from the study due to failure of the blockade. The Ropi Group showed maximal FVC reduction at 30 minutes (25.1%), with a tendency for recovery from this point on. With bupivacaine, the reduction in FVC was less important at the different study moments; an additional reduction was observed between 30 (15.8%) and four hours (17.3%), but it was not statistically significant. A tendency for recovery was observed from four hours on. In both groups, the FVC six hours after the blockade was still below baseline levels., Conclusions: Interscalene block reduces FVC in most cases. Changes were more pronounced in the Ropivacaine group.

Viral entry is an early stage and specific of the infection in which different viral and cellular targets are accessible to therapeutic treatment. CXCR4 and CCR5 act in this process as coreceptor molecules of HIV for its entry into the host cell. The predominant role played by the CCR5 coreceptor in the transmission and spreading of HIV makes this molecule the target of choice for blocking this mechanism. In the last few years, different specific inhibitors of HIV coreceptors have been generated of which only one, Maraviroc, has been approved for clinical use. The synthetic inhibitors developed act as allosteric antagonists that induce a non-permissive state or configuration of the coreceptor for binding viral envelope-glycoproteins. The CCR5 antagonists act on a wide spectrum of viruses with affinity or tropism for this receptor (virus R5), are absorbed orally and have powerful antiviral activity. However, the optimistic perspective offered by these new molecules has to be moderated due to the possible and expected appearance of viral resistances, on the one hand, and the propagation of viral species with affinity or tropism for the CXCR4 receptor (virus X4). This situation is a reality verified in the first clinical trials with these drugs and they acutely and urgently show the need to have effective and non-toxic CXCR4 inhibitors available to block this alternative viral replication and escape route.

Objective: To compare the analgesic efficacy, pharmacokinetics and histamine release of ropivacaine and bupivacaine with fentanyl in continuous epidural perfusion during labor and childbirth., Material and Methods: Prospective study of 40 women at full-term pregnancy who requested epidural analgesia. The patients were randomly assigned to 2 groups of 20: group R received an initial bolus dose of 10 mL of 0.25% ropivacaine and group B received 0.25% bupivacaine, followed in both groups by epidural infusion of the assigned drugs at a concentration of 0.125% plus 0.30 mg of fentanyl at a rate of 5 mL/h through a patient-controlled analgesia device that allowed additional bolus doses. The studied variables were age, weight, height, sensory and motor block, mean blood pressure and maternal-fetal heart rates, number of bolus doses, total local anesthetic administered, duration and type of delivery, oxytocin increase, Apgar at 1 and 5 minutes, plasma levels of local anesthetic (30 minutes after the initial dose, at the end of dilation, in the umbilical vein, and 30 minutes after switching off the perfusion pump), time to clearance, elimination half-life, and a test of histamine release by radioimmunoassay., Results: No significant differences were observed in the course of labor or in Apgar scores. The plasma concentrations of ropivacaine were higher than those of bupivacaine (p<0.03). Clearance of both drugs was similar. The elimination half-life of ropivacaine was significantly less than that of bupivacaine (5.2 +/- 0.7 h vs. 10.8 +/- 1.06 h)., Conclusions: Analgesia was equally effective in both groups, without adverse maternal-fetal effects, with spontaneous micturition and absence of motor blockade in both groups. The plasma concentrations were higher with ropivacaine but were not toxic.

Objective: To compare the analgesic efficacy and extent of motor block when 0.125% ropivacaine or 0.125% bupivacaine were given in continuous perfusion through an epidural catheter during labor., Patients and Methods: We studied 60 ASA I-II women, each carrying a single fetus at full term and in spontaneous labor. The patients were distributed in 2 groups. Women in the ropivacaine group (R) (n = 30) received 8 mL of 0.2% ropivacaine for analgesic induction, followed by a continuous perfusion of 10 mL/h at 0.125%. The bupivacaine group (B) (n = 30) received bupivacaine at the same concentration and infusion rate. The objective of analgesia was to achieve a score less than 3 on a visual analog pain scale. If analgesia was inadequate, a 5 mL bolus of 0.2% ropivacaine or bupivacaine, depending on group, was administered. The motor block was evaluated on an abbreviated Bromage scale and we recorded hemodynamic stability, fetal status, type of delivery and the total dose of local anesthetic., Results: Analgesia and hemodynamics were similar in both groups. Group R required a larger number of additional boluses, although the difference was not statistically significant. A motor block was observed in 8 patients in group B and 1 in group R (p < 0.05). Fetal status was similar in both groups., Conclusion: Both drugs were equally effective for controlling the pain accompanying labor, such that ropivacaine offered no advantage over bupivacaine in that regard. Ropivacaine's reduced motor block effect at the doses administered may offer an advantage in some situations, such as when a walking epidural is provided.

Objectives: To compare the clinical efficacy of hyperbaric 0.5% ropivacaine and 0.5% bupivacaine in subarachnoid blockade for ambulatory surgery., Material and Method: Randomized double-blind study of 90 patients undergoing lower abdominal surgery. Subarachnoid blockade was achieved with 0.5% ropivacaine (12.5 mg) or 0.5% bupivacaine (12.5 mg) in 10% glucose. We recorded age, sex, weight, latency, extension of motor and sensory blocks, duration of surgery, side effects and quality as perceived by the surgeon and the patient., Results: The two groups were similar with respect to latency time and extension of sensory block. Durations of motor (68.9 +/- 22.9 min) and sensory (127.0 +/- 24.3 min) blocks were significantly shorter with ropivacaine than with bupivacaine (133.3 +/- 29.4 and 174.9 +/- 25.5 min, respectively). Patients in the ropivacaine group also experienced a less intense motor block (Bromage 1, 11.1% vs. 93.3%) and fewer episodes of hypotension 0% vs. 17.7%) or bradycardia (4.4% vs. 8.8%) than those in the bupivacaine group. No neurotoxic effects or instances of postdural puncture headache were recorded., Conclusions: Hyperbaric 0.5% ropivacaine offers certain advantages over hyperbaric 0.5% bupivacaine for subarachnoid block in outpatient surgery. Duration and intensity of the sensory-motor blockade is less with ropivacaine and fewer cardiovascular side effects develop.

Objective: To compare the analgesic efficacy of epidural administration of 0.2% ropivacaine alone to that of 0.1% ropivacaine plus 0.0002% fentanyl during childbirth., Patients and Methods: We performed a prospective, randomized single-blind study of 84 women in labor (aged 16 to 40 y, ASA I-II, weight over 110 kg, height over 150 cm, gestational age 37 to 42 weeks). The women were randomly assigned to two groups: group I consisted of 42 patients who received an initial bolus of 10 ml of ropivacaine 0.2% followed by continuous perfusion of ropivacaine 0.2% at a rate of 6 to 10 ml/h; group II was composed of 42 women who received an initial bolus of ropivacaine 0.2% with 50 micrograms of fentanyl followed by continuous infusion of ropivacaine 0.1% and fentanyl 2 micrograms/ml at a rate of 6 to 10 ml/h. Data recorded were parity and type of delivery, blood pressure, heart rate (HR), time to onset of pain relief, motor blockade on a modified Bromage scale, pain on a visual analog scale (VAS) and fetal HR, Apgar score and arterial and venous pH of umbilical blood., Results: We found no significant differences in demographic or hemodynamic data in mothers or fetuses, in type of delivery or motor block, although the latter tended to be slightly lower in group II. In group II, the total anesthetic dose used was significantly lower (p = 0.003); time until onset of pain relief was significantly shorter (p = 0.044); and VAS scores were significantly lower at 15 min (p = 0.005), 30 min (p = 0.029), 60 min (p = 0.017) and 90 min (p = 0.002). The number of top-up boluses needed for deliveries involving instruments was significantly greater in group II (p = 0.37)., Conclusion: The protocol of ropivacaine 0.1% with 2 micrograms/ml of fentanyl provides satisfactory analgesia throughout labor, allowing lower doses of local anesthetic to be used, with shorter onset of pain relief and reduced motor blockade; however the analgesia provided is insufficient for deliveries assisted by instruments.

This paper describes the pharmacological, pharmacokinetic and pharmacodynamic features of ropivacaine on both an experimental and clinical level. Ropivacaine is an amide-type local anesthetic whose chemical structure is related to that of mepivacaine and bupivacaine and whose duration of effect falls between the two. Ropivacaine is a less potent effector of motor blockade than bupivacaine, and its toxic effects on the central nervous system and myocardial tissue is likewise less. Ropivacaine has been employed for epidural anesthesia and analgesia (including through a caudal approach), for peripheral motor blockade, for local infiltration (in gel form), and for intravenous regional anesthesia in ophthalmologic surgery involving peri- and retrobulbar blockade. Subarachnoid use has not yet been accepted in Spain, although phase IV clinical trials of this application have begun. Concentrations of 2 mg/ml (0.2%) and 7.5 mg/ml (0.75%) and 10 mg/ml (1%) are available in Spain.

Chronic administration of Hexachlorobenzene, with or without the simultaneous administration of Tioctamide was assayed. Hexachlorobenzene alone produced the characteristic porphyria, detected through an increase of the urinary excretion and the hepatic accumulation of porphyrins, as well as by a decrease of the Uroporphyrinogen decarboxylase activity. The content of hepatic conjugated dienes did not change while those of malondialdehyde increased, although without reaching levels of statistical significance. These results would indicate the occurrence of an light lipid peroxidation process. The Thioctamide (25 mg/kg body weight) produced more noxious effects than protective ones, which were detected by a high level of Glutamate piruvate transaminase activity and a decrease of the hepatic Uroporphyrinogen decarboxylase activity, at its first step of decarboxylation. These results might indicate that: 1) high doses of Thioctamide decreases Uroporphyrinogen decarboxylase activity, masking its possible protective effect from Hexachlorobenzene's action through free radicals production and, 2) Uroporphyrinogen decarboxylase is a more sensitive parameter than conjugated dienes or malondialdehyde levels to assay the free radicals in vivo Hexachlorobenzene production. In any case, the Thioctamide assayed in lower and non toxic doses, perhaps might protect against Hexachlorobenzene's action through its free radical scavenger ability.