Patients' vs nurses' assessments of postoperative pain and anxiety during patient- or nurse-controlled analgesia.
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We have compared patients' and nurses' assessments of postoperative pain and anxiety after different analgesic treatments. Sixty orthopaedic patients were allocated randomly to receive i.v. piritramide (either nurse-controlled or patient-controlled) or subarachnoid bupivacaine (nurse-controlled or patient-controlled). Patients and nurses assessed pain and anxiety using a visual analogue scale (VAS; 1-100 mm). Pain and anxiety ratings of patients and nurses were significantly correlated (Spearman's r > or = 0.69; P < 0.001). In general, patients' pain scores were higher than nurses' scores (patients' median VAS = 34 (range 1-76) mm; nurses VAS 21 (1-59) mm) and for all groups except the patient-controlled subarachnoid bupivacaine group, where they were significantly higher (P < 0.01). Discrepancy in pain estimates between patients and nurses increased with the level of pain. The relationship between patients' and nurses' anxiety scores was less clearly defined and did not depend on the level of anxiety. (+info)
Iontophoretically applied lidocaine reduces pain on propofol injection.
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We have compared iontophoretically and locally applied lidocaine for relief of pain on propofol injection. Pain was assessed on insertion of a 20-gauge i.v. cannula and at 10-s intervals for 30 s after injection of propofol. Pain scores on cannulation were significantly less in the iontophoresis group (median 1.1) than in the sham (control) group (median 2.8) (P < 0.005). Pain after injection of propofol was significantly reduced at 10 (P < 0.002), 20 (P < 0.001) and 30 s (P < 0.001). We conclude that iontophoretically applied lidocaine decreased the pain of cannulation and propofol injection. (+info)
Effect of bupivacaine on ATP-dependent potassium channels in rat cardiomyocytes.
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Bupivacaine induces fatal arrhythmia when accidentally injected i.v. or overdosed, whereas lidocaine is used as an anti-arrhythmic agent. We have suggested recently that the anti-arrhythmic effect of lidocaine may be explained by suppression of ATP-sensitive potassium (KATP) channels. Therefore, it could be argued that different sensitivities of KATP channels to both drugs could be a reason for their different arrhythmic and anti-arrhythmic properties. In this study, we have investigated the direct action of bupivacaine on KATP channels in cardiomyocytes. The effects of bupivacaine on the cardiac KATP channel were investigated using the patch-clamp technique on enzymatically dissociated cardiomyocytes of adult rats. Bupivacaine was applied to the outer side of excised membrane patches using a multiple-barrel perfusion system. Concentration-response curves indicated that bupivacaine blocked the mean current of the KATP channels at a half-maximum inhibiting concentration (IC50) of 29 mumol litre-1, similar to that reported for lidocaine (43 mumol litre-1). Binding of bupivacaine influenced the gating of this channel, but did not reduce the conductance of the open channel. Bupivacaine and lidocaine were equipotent in blocking KATP channels. However, because of its excessive block of the sodium channel in the inactivated state, block of KATP channels by bupivacaine will only enhance its cardiotoxicity. (+info)
Discriminative stimulus effects of morphine in squirrel monkeys: stimulants, opioids, and stimulant-opioid combinations.
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Morphine and other mu opioids mimic and/or modulate the discriminative stimulus (DS) effects of cocaine, possibly reflecting mutual stimulation of mesolimbic dopamine activity. Less is known about the capacity of cocaine and related stimulants to modulate the DS effects of morphine. The present study investigated the effects of cocaine, amphetamine, and reference drugs, administered alone and with morphine, in squirrel monkeys trained to discriminate morphine from vehicle. Additional studies determined the ability of opioid and dopamine receptor antagonists to attenuate the DS effects of morphine and the morphine-like effects of other drugs. The DS effects of morphine were mimicked by the mu-opioid agonist fentanyl but not the delta-opioid agonists SNC 80 and BW 373U86 or the kappa-opioid agonist U50,488H, and were antagonized by the opioid antagonist naltrexone but not the dopamine antagonist flupenthixol. In three of five monkeys, the DS effects of morphine also were mimicked by cocaine, amphetamine, and the dopamine transport inhibitor GBR 12909 but not the norepinephrine transport inhibitor talsupram or the serotonin transport inhibitor fluoxetine, and were antagonized by flupenthixol but not naltrexone. In this subgroup, pretreatment with cocaine or amphetamine enhanced the DS effects of morphine, whereas in the other two monkeys pretreatment with either stimulant attenuated the DS effects of morphine. The results demonstrated individual differences in morphine-like DS effects of stimulants that are mirrored by individual differences in their interactions with morphine. Furthermore, different mechanisms appear to mediate the DS effects of morphine and the morphine-like DS effects of cocaine and amphetamine. (+info)
Tetracaine can inhibit contractions initiated by a voltage-sensitive release mechanism in guinea-pig ventricular myocytes.
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1. Effects of tetracaine on membrane currents and cell shortening were measured with high resistance electrodes, single-electrode voltage clamp (switch clamp) and a video edge detector at 37 C in cardiac ventricular myocytes. 2. Sequential voltage steps from -65 mV to -40 and 0 mV were used to activate two mechanisms of excitation-contraction (EC) coupling separately. The step to -40 mV activated the voltage-sensitive release mechanism (VSRM); the step to 0 mV1 activated Ca2+-induced Ca2+ release (CICR) coupled to inward Ca2+ current (IL). 3. Exposure to 100-300 microM tetracaine inhibited VSRM contractions but not CICR contractions. Inhibition of VSRM contractions was independent of INa blockade. In contrast, 100 microM Cd2+ blocked IL and CICR contractions, but not VSRM contractions. Simultaneous application of both agents blocked both mechanisms of EC coupling. 4. Contraction-voltage relationships were sigmoidal when the VSRM was available. However, when the VSRM was inhibited with 100-300 microM tetracaine, contraction-voltage relationships became bell-shaped. The tetracaine-insensitive contractions were abolished by 0.1 microM ryanodine, indicating that they were dependent on release of SR Ca2+. 5. At a higher concentration (1 mM) tetracaine also inhibited IL and contractions triggered by IL; however, the time course of effects on IL and associated contractions were different than for VSRM contractions. 6. With continuous application of tetracaine, the VSRM remained inhibited although SR Ca2+ stores increased 4-fold as assessed with caffeine. CICR contractions were not inhibited and maximum amplitude of contraction was not reduced. 7. Rapid application of tetracaine just before and during test steps also inhibited VSRM contractions, but without significantly affecting sarcoplasmic reticulum (SR) Ca2+ stores or CICR contractions. Maximum amplitude of contraction was reduced. 8. Rapid application of tetracaine (100-300 microM) allows preferential inhibition of the VSRM and provides a pharmacological method to assess the contribution of the VSRM to EC coupling. (+info)
Randomized, controlled trial of bupivacaine injection to decrease pain after laparoscopic cholecystectomy.
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OBJECTIVES: To determine if intraoperative instillation of bupivacaine would decrease early postoperative pain after laparoscopic cholecystectomy, if the patients would consequently require less narcotic postoperatively and if such patients would elect to be discharged on the day of operation if given the choice. DESIGN: Double-blind, randomized, controlled trial. SETTING: A tertiary care hospital in Hamilton, Ont. PATIENTS: Fifty patients underwent laparoscopic cholecystectomy. Day-surgery patients had the choice of staying overnight for discharge the following day. They were compared with a control group of 47 patients who had laparoscopic cholecystectomy but did not receive bupivacaine. INTERVENTION: Instillation of 20 mL of 0.5% bupivacaine with epinephrine into laparoscopic cholecystectomy port sites intraoperatively before closure. MAIN OUTCOME MEASURES: Visual analogue scale (VAS) pain scores assessed 4 times postoperatively, the choice of patients to leave hospital the same day or to remain in the hospital overnight; the level of postoperative narcotic usage. MAIN RESULTS: Mean VAS pain scores (range 0 [no pain] to 5 [severe pain]) at less than 2 hours and at 6 hours after surgery were 2.9 and 2.9, respectively, in the bupivacaine group compared with 4.5 and 4.0, respectively, in the control group (p = 0.001 and 0.025). VAS scores at 10 hours postoperatively and the next morning did not differ between the groups. More patients in the bupivacaine group elected to go home on the day of surgery (p = 0.034). Narcotic usage was not significantly different. CONCLUSION: Instillation of bupivacaine into port sites should be standard practice for elective laparoscopic cholecystectomy. (+info)
Studies on sulfation of synthesized metabolites from the local anesthetics ropivacaine and lidocaine using human cloned sulfotransferases.
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The metabolism of the local anesthetics lidocaine and ropivacaine (ropi) involves several steps in humans. Lidocaine is mainly hydrolyzed and hydroxylated to 4-OH-2,6-xylidine (4-OH-xyl). The metabolism of ropi, involving dealkylation and hydroxylation, gives rise to 3-OH-ropi, 4-OH-ropi, 3-OH-2'6'-pipecoloxylidide (3-OH-PPX), and 2-OH-methyl-ropi. Because the metabolites are hydroxylated, they are particularly prone to subsequent Phase II conjugation reactions such as sulfation and glucuronidation. This study focused on the in vitro sulfation of these metabolites as well as another suspected metabolite of ropi, 2-carboxyl-ropi. All the metabolites were synthesized for the subsequent enzymatic studies. Five cloned human sulfotransferases (STs) were used in this study, namely, the phenol-sulfating form of ST (P-PST-1), the monoamine-sulfating form of ST (M-PST), estrogen-ST (EST), ST1B2, and dehydroepiandrosterone-ST (DHEA-ST), all of which are expressed in human liver. The results demonstrate that all of the metabolites except 2-OH-methyl-ropi and 2-carboxyl-ropi can be sulfated. It was also found that all of the STs can conjugate the remaining hydroxylated metabolites except DHEA-ST. However, there are large differences in the capacity of the individual human ST isoforms to conjugate the different metabolites. P-PST-1 sulfates 3-OH-PPX, 3-OH-ropi, and 4-OH-xyl; M-PST and EST conjugate 3-OH-PPX, 3-OH-ropi, and 4-OH-ropi whereas ST1B2 sulfates only 4-OH-xyl. The most extensively sulfated ropi metabolite is 3-OH-PPX. In conclusion, all of the hydroxylated metabolites of lidocaine and ropi can be sulfated if the hydroxyl group is attached to the aromatic ring in the metabolites. The human ST enzymes that are considered to be responsible for the sulfation of these metabolites in vivo are P-PST-1, M-PST, EST, and ST1B2. These enzymes are also found in the liver; this is the most important tissue for the metabolism of ropi in humans, demonstrated by. (+info)
Percutaneous penetration of local anesthetic bases: pharmacodynamic measurements.
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Local anesthetics do not penetrate readily through human skin if applied in their salt form; however, if applied in their base form various effects may be observed, such as a decrease in pricking pain and a change in burning, itch, and thermal sensations. These effects occur after skin penetration and may be attributed to the action of the anesthetics on nociceptors and thermoreceptors, i.e., on C and Adelta nerve fiber respectively. As there is little known about the time course of the pharmacodynamic response of cutaneously applied local anesthetic bases, this study was conducted to characterize various local anesthetics pharmacodynamically by measuring thermal thresholds over time with a thermal sensory analyzer. The results show that the investigated local anesthetics affect thermal thresholds to a different extent, with tetracaine and lidocaine being most efficient. From the response versus time profiles of all eight study subjects various response parameters were obtained: only the cold sensation parameters proved suitable for characterization of the local anesthetics, possibly because cold receptors are located in the epidermis and can easily be reached. Lag times of onset are short and the maximum anesthetic effect is reached within 2-3 h. Cold sensation parameters correlate linearly with the solubility of the local anesthetic bases in medium chain triglycerides and with the drug flux of 50% saturation, indicating that medium chain triglycerides may have similar properties with regard to the local anesthetics solubility as the stratum corneum lipids. (+info)