Comparative analysis of caudal ropivacaine with clonidine vs ropivacaine alone with regards to hemodynamic changes, analgesic potency and side effects in children

Pain management is an essential component of care provided by pediatric anaesthesiologists. That specially holds true due to inability of this group of patients to report their overall experience of surgical procedures like adults. Caudal analgesia is one of the most popular regional anaesthetic techniques employed in children undergoing surgery for lower abdominal, urological, and lower limb operations. Of all the major advantages that this technique has, there is one major disadvantage of short duration of anesthesia. In children it is observed that combination of ropivacaine and clonidine administered caudally has shown to prolong the effects of analgesia. The present clinical study is therefore undertaken to compare caudal ropivacaine with clonidine and ropivacaine alone with regards to hemodynamic changes, analgesic potency and side effects in children. This study included 60 children of the age group 5-10 years ASA grade I and II, of either sex, coming for various elective infra-umbilical surgical procedures who were divided into two groups each comprising of 30 subjects. Group A received plain 0.20% Ropivacaine (1ml/kg) and Group B received 0.20%Ropivacaine (1ml/kg) with clonidine 1µg/kg and the effects were analysed on various parameters.In our study, we chose 0.20% ropivacaine which provides better quality of analgesia and clonidine 1.0μg/kg which prolongs the duration of analgesia significantly while avoiding the side effects like excessive sedation and bradycardia associated with higher doses. Other hemodynamic parameters did not differ significantly in both the groups.

Methadone or Butorphanol as Pre-Anaesthetic Agents Combined with Romifidine in Horses Undergoing Elective Surgery: Qualitative Assessment of Sedation and Induction

While butorphanol is the most commonly used opioid in horses, methadone is not licensed in most countries. Our aim was to compare the effects of both drugs, combined with romifidine, regarding the quality of sedation and induction in horses undergoing elective surgery. Results indicate the suitability of both methadone and butorphanol in this patient population. Animals were scored 10 min after intravenous injection of sedatives. Despite lower overall sedation (OS) score in horses receiving methadone (p = 0.002), the quality and time of induction and intubation remained unchanged. None of the horses had the lowest OS score (no sedation), nor the highest score for ataxia (horse falling). Methadone induced a tendency for minor noise reaction yet minor head lowering scores, the latter being probably the most influencing parameter when scoring OS. Measured physiological parameters decreased in both groups, with greater bradycardia recorded after methadone (p = 0.017), including a higher incidence of atrioventricular blocks that resolved during general anaesthesia. The quality of induction was good–excellent in most of the animals. While comparisons between the degree of antinociception were beyond the scope of this study, analgesic potency might influence the choice when considering opioids as pre-anaesthetic drugs in combination with romifidine before surgery in equines.

AT-121, ¿el opioide perfecto?

Los opioides son los analgésicos más potentes y efectivos de que disponemos en la actualidad. Su cara oscura la encarna el creciente aumento de pacientes adictos a su consumo en todo el mundo, principalmente en Estados Unidos. Desde el descubrimiento de los primeros opioides sintéticos, la industria farmacéutica se halla en busca de un analgésico que no genere tolerancia ni dependencia, ni efectos adversos respiratorios. La mayoría de los opiáceos son agonistas del receptor mu, cuya activación aumenta la disponibilidad sináptica de dopamina, neurotransmisor vehicular en circuitos de recompensa. Sin embargo, un cuarto receptor opioide ha sido descrito recientemente: el receptor de nociceptina/orfanina. Su activación inhibe la liberación de dopamina, evitando el refuerzo positivo que ocurre tras el consumo del fármaco. AT-121 es un agonista bifuncional MOP/NOP que ha sido probado en primates no humanos con resultados prometedores en cuanto a potencia analgésica, menores efectos secundarios sistémicos y menor tasa de adicción y abuso. Tales características hacen de esta molécula un arma esperanzadora en el tratamiento del dolor crónico o de la propia adicción a fármacos opioides. En los últimos años se han explorado distintos agonistas bifuncionales en roedores y primates no humanos con interesantes resultados; quedamos pues a la espera de futuras investigaciones en humanos. ABSTRACT Is AT121 the perfect opioid? Opioids are the most powerful and effective analgesics available today. Their dark side is reflected in the growing number of patients addicted to their use around the world, mainly in the United States. Since the discovery of the first synthetic opioids, the pharmaceutical industry has been searching for an analgesic that does not generate tolerance or dependence, nor adverse respiratory effects. Most opioids are mu receptor agonists, whose activation increases the synaptic availability of dopamine, a neurotransmitter that is a carrier in reward circuits. However, a fourth opioid receptor has recently been described: the nociceptin/orphanine receptor. Its activation inhibits the release of dopamine, preventing the positive reinforcement that occurs after drug consumption. AT-121 is a bifunctional MOP/NOP agonist that has been tested in non-human primates with promising results in terms of analgesic potency, fewer systemic side effects, and lower rate of addiction and abuse. Such characteristics make this molecule a hopeful weapon in the treatment of chronic pain or addiction to opioid drugs. In recent years, different bifunctional agonists have been explored in rodents and non-human primates with interesting results; we are therefore awaiting future research in humans.

Comparative evaluation of subarachnoid block with low dose bupivacaine and fentanyl versus low dose bupivacaine and sufentanil in patients undergoing inguinal surgeries

<p class="abstract"><strong>Background:</strong> Fentanyl is a phenylpiperidine derivative synthetic opioid agonist. As an analgesic fentanyl is 75-125 times more potent than morphine. Sufentanil is a semisynthetic thienyl analogue fentanyl with analgesic potency 5 to 10 times more than that of fentanyl. Recently there has been an interest in using analgesics and local anaesthetics in an attempt to decrease the local anaesthetic dose enabling faster recovery.</p><p class="abstract"><strong>Methods:</strong> A double blinded randomised study was carried out with 50 patients of ASA grade I and II aged between 20 and 60 years undergoing elective inguinal and below inguinal region surgeries under low dose spinal anaesthesia. Patients received 10 mg of 0.5% hyperbaric bupivacaine with 50 μg of fentanyl added to a total volume of 3 ml (group F), and with sufentanil 5 μg [diluted with 5% dextrose] and volume made to 3 ml (group S). Postoperative VAS score for pain, duration of motor block and complications postoperatively is noted.</p><p class="abstract"><strong>Results:</strong> Prolonged postoperative analgesia was observed in group F (216.7 min) and group S (264.8) which was statistically significant among the groups (p&lt;0.001) is higher in group S and also duration of motor block in group F (130.6) and group S (90.5) which was statistically significant among the groups (p&lt;0.001) which is higher in group F than group S.</p><p><strong>Conclusions: </strong>When compared to intrathecal bupivacaine-fentanyl combination; intrathecal bupivacaine-sufentanil combination provided prolonged postoperative analgesia with a lesser duration of motor blockade thus allowing early post operative ambulation.</p>

Stability and Hydrolysis of Desomorphine-Glucuronide

Desomorphine, the principal opioid in Krokodil, has an analgesic potency approximately ten-times that of morphine. Similar to other opioids, during phase II metabolism it undergoes conjugation with glucuronic acid to form desomorphine-glucuronide. Although hydrolysis of conjugated species is sometimes required prior to analysis, desomorphine-glucuronide has not been fully investigated. In this study, six hydrolysis procedures were optimized and evaluated. Deconjugation efficiencies using chemical and enzymatic hydrolysis were evaluated and stability in aqueous solution was assessed. Acid hydrolysis was compared with five β-glucuronidase sources (BGTurbo™, IMCSzyme™, Escherichia coli, Helix pomatia and Patella vulgata). At optimal conditions, each hydrolysis method produced complete hydrolysis (≥96%). However, under simulated challenging conditions, P. vulgata was the most efficient β-glucuronidase for the hydrolysis of desomorphine-glucuronide. Both BGTurbo™ and IMCSzyme™ offered fast hydrolysis with no need for sample cleanup prior to liquid chromatography-quadrupole/time of flight-mass spectrometry (LC-Q/TOF-MS) analysis. Hydrolysates using E. coli, H. pomatia and P. vulgata underwent additional sample treatment using β-Gone™ cartridges. Additionally, the stability of free and conjugated drug was evaluated at elevated temperature (60°C) in aqueous solutions between pH 4 and 10. No degradation was observed for either desomorphine or desomorphine-glucuronide under any of the conditions tested.