Summary The authors investigated the antinociceptive activity of tadalafil and adrenergic agents co-administered in the writhing test in mice. The intensity of nociception was quantified by the number of writhes occurring between 0 and 30 min after stimulus injection. Nontreated groups (NT) received acid intraperitoneally (ip) followed by sterile saline (ip). Animals received (ip) tadalafil (2.5 or 5 mg/kg), Metoprol (2 or 5 mg/kg) or methyl dopa (62.5 or 125 mg/kg) 30 min before acid injection. It was observed that only the largest doses of every drug inhibited the number of writhes in mice. In another series of experiments, animals were pretreated with the lower ineffective doses of metoprolol and methyl dopa. After 30 min, mice also received the lower ineffective dose of tadalafil followed by acid injection. The combination of ineffective doses of metoprolol and methyldopa with tadalafil significantly inhibited the nociceptive response induced by acetic acid injection. Data obtained from these experiments showed that ineffective doses of tadalafil associated with ineffective doses of adrenergic agents provided analgesic effects in the writhing test.
The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25-mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell-depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell-depleted C3H mice. T reg cell-depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell-depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility.
Introduction: Various adjuvants have been used intrathecally to improve the quality and duration of the spinal anaesthesia along with better postoperative analgesia We studied the effect of dexmedetomidine as intrathecal adjuvant to local anaesthetic agent in subarachnoid block. The primary goal was to study the onset and duration of sensory and motor block. The secondary goal was to note the time for first rescue analgesic, total requirement of rescue analgesic, quality of block and any complications.
Materials and Method: Sixty patients age 18 to 60 years, ASA I-II , posted for lower limb orthopaedic surgeries were randomly allocated into two equal groups based on computer generated randomization: Group B: Inj.Bupivacaine 0.5% hyperbaric 3ml(15mg) + 0.15cc normal saline. Group D: Inj.Bupivacaine 0.5% hyperbaric 3ml(15mg) + Inj.Dexmedetomidine 15µg(0.15ml). All the patients were observed for onset of sensory and motor block, two segment regression time, total sensory and motor block duration, time to first rescue analgesic, total number of doses of rescue analgesia in 24 hours postoperatively and side effects if any.
Results: The demographic variables were comparable in the two groups. The onset of sensory block was faster in group B (p=0.002) with no significant difference in the onset of motor block in two groups. The duration of sensory and motor block in Group D was significantly prolonged (p
EDITOR: Non-depolarizing muscle relaxants retain a vital place in anaesthetic practice. The number of available muscle relaxants has increased in recent years. All of these drugs vary in speed of onset, duration of action and in speed of offset. The manufacturers produce guidance for the use of these drugs in the form of data sheets. These may give recommendations for initial dose, speed of onset and duration of action. Clinical practice is however, likely to vary considerably with the manufacturer's guidance for the following reasons: 1. Variable individual response to muscle relaxants. Marked variation has been shown between healthy individuals for the same dose of muscle relaxant [1] 2. Renal function. Impaired renal function may prolong the duration of action. 3. Liver disease or reduced hepatic blood flow. These may prolong the duration of action. 4. Electrolyte disturbances. These may prolong the duration of action. 5. Other drugs. Aminoglycosides prolong the duration of action, other drugs may also affect the duration of action. 6. Obesity. Dose requirements are affected with variation between the different muscle relaxants. Knowledge about the state of neuromuscular blockade is important from induction through to recovery. Inadequate neuromuscular blockade during the procedure may make surgery difficult, and has the potential to be extremely dangerous to the patient. At the end of the procedure there is the potential for an awake patient with residual paralysis or for recurarization during the recovery period. Residual neuromuscular blockade may increase the risk of postoperative pulmonary complications [2]. The peripheral nerve stimulator is not the perfect monitor; it measures neuromuscular function in the periphery, which is more sensitive to non-depolarizing muscle relaxants than is diaphragmatic muscle [3]. It may give an inaccurate test due to poor electrical contact or incorrect placement. At present, it is the most common monitor of neuromuscular function. This is due to its simplicity, ease of use, portability and cost. We have undertaken a survey to establish current practice in respect of PNS usage at five hospitals. We aimed to assess use and availability of the PNS. We also wanted to identify the factors which influence PNS usage, such as duration of anaesthesia and the muscle relaxant used. A questionnaire was sent to all grades of anaesthetist at five hospitals. Three teaching hospitals and two district general hospitals. The questionnaire asked a number of questions about PNS usage. One hundred questionnaires were returned with a response rate of 57%, of these, replies were from consultants (48%), from training grades (48%) and from other grades (4%). Question 1: Is there a place for using a peripheral nerve stimulator while using a non-depolarizing muscle relaxant in your practice? Yes 89% No 11% Question 2: If a PNS is available in the theatre, how often do you use it? Never 8% Sometimes 74% Always 17% Question 3: Will you use a peripheral nerve stimulator if the duration of operation is less than 20 min, 20-40 min, 40-60 min and over 60 min? (Table 1)Table 1: Use of PNS with duration of operation Question 4: How often is a peripheral nerve stimulator available? (Table 2)Table 2: Availability of PNS in theatre (%) Question 5: How often do you use a peripheral nerve stimulator with different muscle relaxants? (Table 3)Table 3: Use of PNS with particular relaxants as percentage The response rate of 57% was disappointing but did show some marked differences. The large majority of anaesthetists (89%) in our survey have a need for a peripheral nerve stimulator in their practice. Most use it for selected cases, with a small group using it for all cases in whom a non-depolarizing muscle relaxant is used (17%). This survey found that a factor affecting usage was the duration of anaesthesia with the number of anaesthetists always using a PNS rising from 11% for operations of 20-40 min duration to 21% always using a PNS for operations of 40-60 min. This may reflect the fact that an induction dose of muscle relaxant will often last between 20 and 40 min, but repeat doses are likely if the duration exceeds 40 min. There appeared to be a relation between the choice of muscle relaxant and the duration of drug action, with the least use for the short-acting mivacurium and most use for the long-acting pancuronium. It was interesting to find no increase in PNS use for the newer agents. This may reflect their predictability, although there are reports of recurarization with rocuronium [4]. It is of concern that in some hospitals there are insufficient nerve stimulators. The Association of Anaesthetists of Great Britain and Ireland recommends that a means of assessing neuromuscular block should be available whenever neuromuscular blocking drugs are used [5]. In the case of one teaching hospital, 40% of respondents reported that peripheral nerve stimulators were 'rarely available' or 'never available'. While their use is not mandatory they should be readily available in every theatre complex. The results of this survey were presented to this hospital and have resulted in the provision of four extra peripheral nerve stimulators for the theatre complex. The use of the PNS helps with anaesthetic training and with the introduction of new or modified muscle relaxants but above all it may improve anaesthetic standards by preventing over- or under-curarization. We are grateful to Dr Hugh James and audit secretary Dawn Burt for their help in carrying out this survey. J. SHAH O. OWEN-SMITH S. COLEY Department of Anaesthesia, Leicester General Hospital NHS Trust, Gwendolen Road, Leicester LE5 4PW, UK J. RANGASAMI Nuffield Department of Anaesthesia, Oxford, UK
Background and objective Insertion of the laryngeal mask airway in the anaesthetized patient can sometimes be difficult and propofol has been advocated as the anaesthetic induction agent of choice because of its depressant effect on laryngeal reflexes compared with other intravenous anaesthetics. However, when used as the sole induction agent, relatively large doses of propofol are required to achieve successful laryngeal mask insertion. This has cost implications and may produce unwanted cardiorespiratory depression. Methods One hundred and forty-two patients were randomized to receive either: fentanyl 1 µg kg−1 and lidocaine 1.5 mg kg−1 (group 1), or fentanyl 1 µg kg−1 and midazolam 0.04 mg kg−1 (group 2), or fentanyl 1 µg kg−1, midazolam 0.04 mg kg−1 and lidocaine 1.5 mg kg−1 (group 3) or fentanyl 1 µg kg−1 (group 4) 2 min before induction of anaesthesia. Anaesthesia was established with propofol infused at 33.3 mg min−1. Results Patients who were given midazolam required significantly less propofol to achieve satisfactory laryngeal mask insertion, median propofol doses: group 1, 1.63 mg kg−1; group 2, 1.16 mg kg−1; group 3, 1.01 mg kg−1; group 4, 1.9 mg kg−1, P < 0.0001 (analysis of variance). Patients given midazolam reported less pain on injection with propofol 13% and 3% groups (2 and 3) compared with 37.5% and 77% (groups 1 and 4) P = 0.002 (χ2). Conclusions Midazolam reduces the dose of propofol required for induction of anaesthesia and successful insertion of the laryngeal mask airway. There was no clinical benefit to be gained from the addition of lidocaine.
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