RESUMEN
BACKGROUND: The mechanism underlying the depressant effect of opioids on neuronal activity within the neocortex is still not clear. Three modes of action have been suggested: (1) inhibition by activation of postsynaptic potassium channels, (2) interaction with postsynaptic glutamate receptors, and (3) presynaptic inhibition of glutamate release. To address this issue, the authors investigated the effects of mu- and delta-receptor agonists on excitatory postsynaptic currents (EPSCs) and on membrane properties of neocortical neurons. METHODS: Intracellular recordings were performed in rat brain slices. Stimulus-evoked EPSCs mediated by different glutamate receptor subtypes were pharmacologically isolated, and opioids were applied by addition to the bathing medium. Possible postsynaptic interactions between glutamate and opioid receptors were investigated using microiontophoretic application of glutamate on neurons functionally isolated from presynaptic input. RESULTS: delta-Receptor activation by d-Ala2-d-Leu5-enkephalin (DADLE) reduced the amplitudes of EPSCs by maximum 60% in a naltrindole-reversible manner (EC50: 6-15 nm). In 30-40% of the neurons investigated, higher concentrations (0.1-1 micrometer) of DADLE activated small outward currents. The mu-receptor selective agonist d-Ala2-N-MePhe5-Gly5-ol-enkephalin (0.1-1 micrometer) depressed the amplitudes of EPSCs by maximum 30% without changes in postsynaptic membrane properties. In the absence of synaptic transmission, inward currents induced by microiontophoretic application of glutamate were not affected by DADLE. CONCLUSIONS: Activation of mu- and delta-opioid receptors depresses glutamatergic excitatory transmission evoked in neocortical neurons by presynaptic inhibition. A weak activation of a postsynaptic potassium conductance becomes evident only at high agonist concentrations. There is no evidence for a postsynaptic interaction between glutamate and opioid receptors.
Asunto(s)
Antagonistas de Aminoácidos Excitadores/farmacología , Neocórtex/efectos de los fármacos , Neuronas/efectos de los fármacos , Receptores AMPA/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores Opioides delta/fisiología , Receptores Opioides mu/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Analgésicos Opioides/farmacología , Animales , Relación Dosis-Respuesta a Droga , Encefalina Ala(2)-MeFe(4)-Gli(5)/farmacología , Leucina Encefalina-2-Alanina/farmacología , Femenino , Antagonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-B , Ácido Glutámico/farmacología , Iontoforesis , Masculino , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Neocórtex/citología , Neocórtex/fisiología , Neuronas/fisiología , Ratas , Ratas Wistar , Receptores AMPA/fisiología , Receptores de GABA-A/fisiología , Receptores de GABA-B/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Receptores Opioides delta/agonistas , Receptores Opioides mu/agonistas , Sinapsis/efectos de los fármacos , Sinapsis/fisiología , Transmisión Sináptica/efectos de los fármacosRESUMEN
Based on a case report, we offer brief guidelines on the perioperative management of patients with Sleep-Apnea-Syndrome (SAS) who present with a high incidence of a difficult airway and a high risk of respiratory depression during the perioperative period. A 39 year old male patient with a body mass index of 34.22 kg/m2 and receiving continuous-positive-airway-pressure-(CPAP) therapy for known SAS was scheduled for elective plastic surgery. After induction of anaesthesia and direct laryngoscopy no adequate airway could be established and the patient became hypoxic, hypercapnic and developed hypotension and bradycardia. With the use of a laryngeal mask airway the patient was stabilized and did not show neurologic sequale after immediate awakening. The following fiberoptic intubation of the awake patient, still showing tendency of upper airway obstruction, confirmed the difficult anatomical structures. The subsequent general anesthesia was uneventful. The patient received CPAP therapy and was monitored during the first postoperative night in the Intensive Care Unit. He made an uneventful recovery. He was advised to have regional anaesthesia or planned fiberoptic intubation, where possible, in the case of further anesthetic intervention. SAS has major implications for the anaesthesiologist and whenever patients exhibiting the high risk factors (obesity, male sex, history of intense snoring, impaired daytime performance, nonrefreshing daytime naps) are presented for surgery this condition should be considered. Elective surgery should be postponed until after adequate examination and treatment when necessary. Patients with SAS should always be suspected of having cardiopulmonary dysfunctions such as hypertension, cardiac dysrhythmia or cor pulmonale. It is most important to avoid sedative premedication, to initiate CPAP therapy preoperatively, to encourage regional anaesthesia if possible and to ensure close monitoring over the complete perioperative period. Planned fiberoptic intubation, preferably with surgical personnel available for an emergency airway, is a safe method for the induction of anaesthesia. Postoperatively, patients are at high risk from respiratory depression, even in the awake state. Postoperative opioid analgesia, no matter what route, should only be given under close monitoring. Independently of regional or general anaesthesia there is an increased risk of respiratory depression in the middle of the first postoperative week, suspected to be caused by the catching up on lost REM-sleep, due to shifts in the normal sleep pattern during the first postoperative days.
Asunto(s)
Anestesia por Inhalación , Síndromes de la Apnea del Sueño/complicaciones , Adulto , Humanos , Complicaciones Intraoperatorias/fisiopatología , Máscaras Laríngeas , Masculino , Respiración con Presión Positiva , Síndromes de la Apnea del Sueño/fisiopatologíaRESUMEN
BACKGROUND: Topical capsaicin is known to be a safe and effective pain management adjunct for rheumatoid arthritis, osteoarthritis, neuralgias, and diabetic neuropathy. However, studies and case reports in the literature have indicated that other conditions may also benefit from capsaicin: painful or itching cutaneous disorders from operations, injuries, or tumors; neural dysfunction; or inflammation of the airways and urinary tract. METHODS: To determine the effectiveness of capsaicin for painful cutaneous disorders and neural dysfunction, the authors analyzed data from 33 reports (MEDLINE search of 1966-96) on the efficacy of capsaicin. Outcome measures consisted of the response rate and degree of pain relief. Results from placebo-controlled trials were pooled when possible; effect of treatment was estimated by the method of DerSimonian and Laird. RESULTS: Pain relief for postmastectomy syndrome and cluster headache was greater with capsaicin than with placebo; also, psoriasis and pruritus responded better to capsaicin. Uncontrolled studies and case reports have indicated that pain or dysfunction was less at the end of capsaicin therapy for neck pain, loin pain/hematuria syndrome, oral mucositis, rhinopathy, reflex sympathetic dystrophy syndrome, detrusor hyperreflexia, and cutaneous pain due to tumor of the skin. CONCLUSIONS: Capsaicin is effective for psoriasis, pruritus, and cluster headache; it is often helpful for the itching and pain of postmastectomy pain syndrome, oral mucositis, cutaneous allergy, loin pain/hematuria syndrome, neck pain, amputation stump pain, and skin tumor; and it may be beneficial for neural dysfunction (detrusor hyperreflexia, reflex sympathetic dystrophy, and rhinopathy). A universal problem for many of the studies analyzed was the absence of a "burning placebo" such as camphor.