Hawa Keita

Predictive factors of early postoperative urinary retention in the postanesthesia care unit

Urinary retention is a common postoperative complication associated with bladder overdistension and the risk of permanent detrusor damage. The goal of this study was to determine predictive factors of early postoperative urinary retention in the postanesthesia care unit (PACU). We prospectively collected, in 313 adult patients, variables including age, gender, previous history of urinary tract symptoms, type of surgery and anesthesia, intraoperative administration of anticholinergics, amount of intraoperative fluids, IV morphine titration, and bladder volume on entry to the PACU. For each patient, bladder volume was measured by ultrasound on entry and before discharge from the PACU. Urinary retention was defined as a bladder volume larger than 600 mL with an inability to void within 30 min. Predictive factors were identified by multivariate analysis. The incidence of urinary retention in the PACU was 16%. In the multivariate analysis only the amount of intraoperative fluids (≥750 mL; P = 0.02; odds ratio = 2.3), age (≥50 yr; P = 0.008; odds ratio = 2.4), and bladder volume on entry to PACU (≥270 mL; P = 0.0001; odds ratio = 4.8) were found to independently increase the risk of urinary retention. Considering the clinical impact of undiagnosed postoperative urinary retention, these results suggest systematic evaluation of bladder volume with a portable ultrasound device in the PACU, especially in patients with risk factors.

Estrous and sex variations in vocalization thresholds to hindpaw and tail pressure stimulation in the rat.

This study examined sex and estrous differences in vocalization thresholds of rats to hindpaw and tail pressure stimulation tested daily throughout at least 3 weeks. When all the measures were pooled, compared to males, female rats had higher thresholds for tail pressure (499 +/- 6 g, n = 188 measures vs. 466 +/- 2 g, n = 144 measures, respectively), but equal thresholds for hindpaw pressure (321 +/- 6 g, n = 188 measures vs. 319 +/- 2 g, n = 144 measures, respectively). Thresholds of female rats in proestrus and estrus were lower than those of rats in metestrus and diestrus for both tail and hindpaw stimulation, whereas those of males did not vary systematically. Thresholds at the two stimulation sites covaried in females but not in males. These results add to the growing list of important interacting factors that underly behavioral sensitivity to noxious somatic stimulation.

Antinociceptive effect of a κ-opioid receptor agonist that minimally crosses the blood-brain barrier (ICI 204448) in a rat model of mononeuropathy

The antinociceptive effect of intraplantar (i.pl.) ICI 204448 ((R,S)-N-[2-(N-methyl-3,4-dichloro-phenylacetamido)-2-(3-carbox yph enyl)- ethyl]pyrrolidine hydrochloride)) (20, 30, 40 and 50 micrograms), a kappa-opioid receptor agonist which has limited access to the central nervous system, was studied in a well-established rat model of peripheral mononeuropathy produced by moderate constriction of the sciatic nerve. Vocalization thresholds to paw pressure were used as a nociceptive test. On the injected nerve-injured paw, ICI 204448 at 20 and 30 micrograms had no significant effect, but higher doses (40 micrograms) produced a significant antinociceptive effect, which plateaued at 50 micrograms. By contrast, no antinociceptive effect was observed on the contralateral paw. The effect of ICI 204448 (40 micrograms) was significantly antagonised by the specific kappa-opioid receptor antagonist nor-binaltorphimine (20 and 30 micrograms), when co-injected in the nerve-injured paw.

Halothane and isoflurane increase spontaneous but reduce the N-methyl-D-aspartate-evoked dopamine release in rat striatal slices: evidence for direct presynaptic effects.

BACKGROUND Experimental data suggest that volatile anesthetics induce significant changes in extracellular dopamine concentrations in the striatum, a restricted but functionally important brain area. In the present study, the authors used a superfused slice preparation to examine the effects of halothane and isoflurane on both spontaneous and N-methyl-D-aspartate (NMDA)-evoked dopamine release in the striatum, and whether these effects involved actions of these anesthetics mediated by gamma-aminobutyric acid receptors in this structure. METHODS Radioactivity collected from 5-min fractions was compared in the absence (basal release) or presence (evoked release) of NMDA alone and combined with various pharmacologic or anesthetic agents in slices of the dorsolateral striatum and synaptosomes of the whole striatum preloaded with 3H-dopamine and superfused with artificial cerebrospinal fluid. RESULTS In tetrodotoxin-treated striatal slices, halothane and isoflurane significantly increased dopamine basal release (EC50 = 0.33 mM and 0.41 mM for halothane and isoflurane, respectively). Both agents decreased the NMDA-evoked dopamine release in both the absence (IC50 = 0.15 mM and 0.14 mM for halothane and isoflurane, respectively) and presence (IC50 = 0.15 mM for both halothane and isoflurane) of tetrodotoxin in slices, and in synaptosomes (IC50 = 0.19 mM for both halothane and isoflurane). NMDA-induced dopamine release was significantly enhanced by bicuculline, a gamma-aminobutyric acid receptor antagonist. Halothane and isoflurane inhibitory effects on NMDA-evoked dopamine release were significantly reduced in the presence of bicuculline. CONCLUSION These results indicate that halothane and isoflurane decrease the NMDA-evoked dopamine release by acting directly at dopamine terminals in striatal slices. They support the involvement of both depression of presynaptic NMDA receptor-mediated responses and enhancement of gamma-aminobutyric acid receptor-mediated responses in these effects.

Halothane and Isoflurane Differentially Affect the Regulation of Dopamine and Gamma-aminobutyric Acid Release Mediated by Presynaptic Acetylcholine Receptors in the Rat Striatum

Background General anesthetics are thought to produce their hypnotic effects mainly by acting at ligand‐gated ionic channels in the central nervous system (CNS). Although it is well established that volatile anesthetics significantly modify the activity of the acetylcholine nicotinic receptors of the neuromuscular junction, little is known about their actions on the acetylcholine receptors in the CNS. In this study, the effects of halothane and isoflurane on the regulation of dopamine (DA) (gamma‐aminobutyric acid [GABA]) depolarization‐evoked release mediated by nicotinic (muscarinic) presynaptic receptors were studied in the rat striatum. Methods Assay for GABA (dopamine) release consisted of3 H‐GABA (sup 3 H‐DA)‐preloaded synaptosomes with artificial cerebrospinal fluid (0.5 ml/min, 37 degrees Celsius) and measuring the radioactivity obtained from 1‐min fractions for 18 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with vaporized halothane and isoflurane (0.5–5%, 5 min), and finally with no pharmacologic stimulation (5 min). The depolarizing agents were potassium chloride (KCl; 9 mM) alone or with acetylcholine (10 sup ‐6 ‐ 10 sup ‐4 M) and/or atropine (10 sup ‐5 M) for experiments with3 H‐GABA, and KCl (15 mM) and nicotine (10 sup ‐7 ‐ 5 x 10 sup ‐4 M) alone or with mecamylamine (10 sup ‐5 M) for experiments with3 H‐DA. Results Potassium chloride induced a significant, Ca2+ ‐dependent release of both3 H‐GABA and3 H‐DA. Nicotine produced a concentration‐related, mecamylamine‐sensitive3 H‐DA release that was significantly attenuated by nicotine (10 sup ‐7 M) preincubation. Acetylcholine elicited a dose‐dependent, atropine‐sensitive reduction of the KCl‐evoked3 H‐GABA release. Halothane and isoflurane significantly decreased the nicotine‐evoked3 H‐DA release but had only limited depressant effects on the KCl‐stimulated3 H‐DA and no action on the KCl‐induced3 H‐GABA release. The effects of acetylcholine on3 H‐GABA release were reversed by halothane but not by isoflurane. Conclusion Clinically relevant concentrations of halothane and isoflurane significantly, but differentially, alter the presynaptic cholinergic regulation of the release of inhibitory neurotransmitters in the striatum. These results suggest that the cholinergic transmission may represent an important and specific presynaptic target for volatile anesthetics in the CNS.

Prophylactic ip injection of bupivacaine and/or morphine does not improve postoperative analgesia after laparoscopic gynecologic surgery.

PurposeTo determine the effectiveness ofip bupivacaine and/or morphine for postoperative analgesia after laparoscopic surgery. A controversy exists on the effectiveness and clinical value ofip injection of local anesthetics for postoperative analgesia. A possible peripheral analgesic effect of morphine afterip injection remains debated as well.MethodsWe conducted a randomized, double-blinded, study to compare the efficacy of prophylacticip administration of 0.9% saline (n = 16), 0.5% bupivacaine (100 mg,n = 15), morphine (3 mg,n = 16) and a mixture with 0.5% bupivacaine (100 mg) and morphine (3 mg,n = 18) to reduce both postoperative pain scores and analgesic requirements after gynecologic laparoscopic surgery. A multimodal analgesia regimen (acetaminophen, nonsteroidal antiinflammatory drugs and morphine) was used for postoperative analgesia.ResultsNo difference was observed in postoperative pain scores (visual analogue scale at rest and on coughing), or analgesic requirements during the first 24 postoperative hours between the four groups. There was also no significant intergroup difference in sedation scores and incidence of nausea and vomiting.ConclusionWhen multimodal postoperative analgesia is used, prophylacticip administration of 100 mg bupivacaine and/or 3 mg morphine does not significantly improve postoperative analgesia in patients undergoing laparoscopic gynecologic surgery.RésuméObjectifDéterminer l’efficacité de l’administration intrapéritonéale ip de bupivacaïne et/ou de morphine pour l’analgésie postopératoire en chirurgie laparoscopique. L’efficacité et la valeur clinique de l’injection ip d’anesthésiques locaux pour l’analgésie postopératoire, de même que l’effet analgésique périphérique possible de la morphine après l’injection ip, demeurent discutables.MéthodeLétude, randomisée et à double insu, voulait comparer l’efficacité de l’administration ip prophylactique de solution saline à 0,9 %(n= 16), de 100 mg de bupivacaine à 0,5 % (n = 15), de 3 mg de morphine (n = 16) et d’un mélange de 100 mg de bupivacaine à 0,5 % et de 3 mg de morphine (n = 18) pour réduire la douleur postopératoire et les besoins analgésiques à la suite d’une intervention gynécologique laparoscopique. Une analgésie multimodale (acétaminophène, anti-inflammatoires non stéroïdiens et morphine) a été utilisée pour l’analgésie postopératoire.RésultatsAucune différence intergroupe n’a été observée quant aux scores de douleur postopératoire (échelle visuelle analogique au repos et pendant la toux) ou aux besoins analgésiques pendant les 24 premières heures postopératoires. Les scores de sédation et l’incidence de nausées et de vomissements n’ont pas présenté non plus de différence intergroupe.ConclusionQuand on utilise une analgésie postopératoire multimodale, l’administration prophylactique ip de 100 mg de bupivacaine et/ou de 3 mg de morphine n’améliore pas signifcativement l’analgésie postopératoire en chirurgie gynécologique laparoscopique.

Age-adapted morphine titration produces equivalent analgesia and adverse effects in younger and older patients.

Background To determine the efficacy and safety of intravenous postoperative morphine titration in the elderly compared with younger patients. Methods In the post‐anaesthesia care unit, patients complaining of pain received morphine until adequate pain relief. Intravenous morphine was titrated as 3 mg boluses in young (age ⩽65 yr) and 2 mg in elderly patients (>65 yr) every 5 min. Results We studied 350 young and 68 elderly patients. There were no significant differences between the two age groups for pain intensity at the onset of titration (numerical rating scale, 7.4 ± 1.7 in young vs. 7.5 ± 1.7 in elderly patients), area under the curve of numerical rating scale vs. morphine boluses (97.7 ± 59.6 vs. 98.2 ± 62), number of boluses required to obtain pain relief (3 ± 1.3 vs. 3 ± 1.3), percentage of titration failures (10% vs. 9%) and incidence of excessive sedation (18% vs. 21%). Renal clearance was significantly reduced in elderly compared with young patients (55 ± 21 vs. 85 ± 15 mL min−1; P < 0.0001). Conclusion Using lower bolus doses, pain relief in the immediate postoperative period with morphine was as efficacious and safe in elderly patients as in younger patients. The decrease in renal clearance of morphine in the elderly justifies the reduction of intravenous morphine boluses for the treatment of postoperative pain.

Riluzole Blocks Dopamine Release Evoked by N-methyl-D-aspartate, Kainate, and Veratridine in the Rat Striatum

Background: Dopamine (DA) is released in large amounts during cerebral ischemia and may exacerbate tissue damage. Riluzole (54274 RP) is a recently developed agent that depresses glutamate neurotransmission in the central nervous system (CNS) and that may protect against ischemic injury in some animal models. Because glutamate stimulates the release of DA in the striatum, the authors hypothesized that riluzole could antagonize DA release in this structure. Methods: Assay for DA release consisted of superfusing3 H‐DA preloaded synaptosomes with artificial cerebrospinal fluid (1 ml/min, 37 [degree sign] Celsius) and measuring the radioactivity obtained from 1‐min fractions over 22 min, first in the absence of any treatment (spontaneous release, 8 min), then in the presence of depolarizing agents combined with riluzole (0.1–100 micro Meter, 5 min), and finally with no pharmacologic stimulation (9 min). The following depolarizing agents were tested: KCl (9, 15 mM), veratridine (0.01–1 micro Meter), N‐methyl‐D‐aspartate (NMDA, 0.1–1 mM), kainate (0.1–1 mM), and nicotine (0.01–0.5 mM). Assay for DA uptake was performed by measuring the radioactivity incorporated in synaptosomes incubated with3 H‐DA (44 nM; 5 min; 37 [degree sign] Celsius). Results: All depolarizing agents produced a significant, concentration‐related increase from basal3 H‐DA release. Riluzole was found to decrease the release induced by veratridine (1 micro Meter), NMDA (1 mM), and kainate (1 mM) in a significant, concentration‐related manner (IC50 = 9.5 micro Meter, 1.6 micro Meter, and 5.8 micro Meter for veratridine, NMDA, and kainate, respectively). In contrast, it did not affect the release elicited by either KCl or nicotine. Riluzole had no significant effect on the specific3 H‐DA uptake. Conclusions: Riluzole produced a potent blockade of the release of DA mediated by activation of presynaptic sodium channels, NMDA, and kainate receptors. Depression of glutamate transmission together with blockade of DA release may contribute to the actions of this agent in vivo.

Anesthetic concentrations of riluzole inhibit neuronal nitric oxide synthase activity, but not expression, in the rat hippocampus

We hypothesized that anesthetic dose of riluzole, an inhibitor of glutamate neurotransmission, may affect the activity and/or expression of neuronal NOS (nNOS). Riluzole, N(G)-nitro-L-arginine-methyl ester (L-NAME) and 7-nitro indazole (7-NI) produced a concentration-related inhibition of nNOS activity in vitro. Riluzole competed with 7-NI for inhibition of nNOS activity, but had no effect on nNOS or endothelial NOS (eNOS) protein expression. Also, nNOS activity was significantly decreased in riluzole-anesthetized rats (40 mg kg(-1) i.p., -32+/-6% from controls, P<0.05). Therefore, blockade of nNOS activity may be involved in the anesthetic effects of riluzole in vivo.

Effects of riluzole on N-methyl-D-aspartate-induced tyrosine phosphorylation in the rat hippocampus

Since increased tyrosine phosphorylation has been observed in response to brain ischemia, we investigated whether riluzole (an inhibitor of glutamate neurotransmission with neuroprotective properties) affects tyrosine phosphorylation stimulated by N-methyl-D-aspartate (NMDA) in rat hippocampal slices. Riluzole produced an extremely potent concentration-related inhibition of NMDA (1 mM)-stimulated protein tyrosine phosphorylation (IC(50)=0.5+/-0.03 microM, mean+/-S.D.), but failed to affect that evoked by phorbol 12-myristate 13-acetate (PMA, an activator of protein kinase C, 0.1 and 1 microM). These results suggest that inhibition of tyrosine phosphorylation may contribute to the neuroprotective effects of riluzole against excitotoxic injury.