Prevención y tratamiento de pacientes con náuseas y vómitos postoperatorios / Prevention and treatment of patients with postoperative nausea and vomiting

Resumen Las náuseas y vómitos postoperatorios (NVPO) son un problema frecuente en los pacientes quirúrgicos. Cuando no son prevenidos adecuadamente pueden provocar mayor morbilidad, estadía prolongada en la unidad de recuperación postoperatoria y hospitalización no planificada. El objetivo del equipo quirúrgico debe ser la profilaxis de las NVPO más que su tratamiento, con el fin de disminuir significativamente su incidencia y complicaciones asociadas. Los principales factores de riesgo para NVPO son: sexo femenino, historia de NVPO en cirugías previas y/o cinetosis, no fumar, uso de opioides sistémicos en el postoperatorio, someterse a ciertos tipos de cirugía (como colecistectomía, cirugía laparoscópica y cirugía ginecológica), utilizar anestésicos volátiles y/u óxido nitroso intraoperatorios, y duración de la cirugía. Sugerimos objetivar el riesgo de NVPO utilizando las escalas de riesgo de NVPO de Apfel o Koivuranta. Los principales fármacos antieméticos usados como profilaxis y tratamiento en el período perioperatorio son dexametasona, ondansetrón y droperidol. Existen estrategias generales que se pueden utilizar para reducir el riesgo quirúrgico basal de NVPO como evitar la anestesia general, privilegiando la anestesia regional, utilizar propofol para la inducción y mantención de la anestesia, evitar el uso de óxido nitroso y/o anestésicos inhalatorios, minimizar el uso postoperatorio de opioides sistémicos y recibir una hidratación intravenosa abundante durante la cirugía. La etiología de las NVPO es multifactorial, por lo que la prevención y tratamiento deben incluir diferentes clases de antieméticos, que actúen sobre los diferentes receptores de náuseas y/o vómitos hasta el momento conocidos, junto con las estrategias generales antes mencionadas.

Abstract Postoperative nausea and vomiting (PONV) are a common problem in surgical patients. When not properly prevented, they can lead to increased morbidity, prolonged stay in the postoperative recovery unit and unplanned hospitalization. The objective of the surgical team should be the prophylaxis of PONV rather than its treatment, in order to significantly reduce its incidence and associated complications. The main risk factors for PONV are: female sex, history of PONV in prior surgeries and/or motion sickness, non-smoking, use of systemic opioids postoperatively, undergo certain types of surgery (such as cholecystectomy, laparoscopic surgery and gynecological surgery), use volatile anesthetics and/or intraoperative nitrous oxide, and duration of surgery. We suggest to objectify the risk of PONV using the Apfel or Koivuranta PONV risk scales. The main anti-emetic drugs used as prophylaxis and treatment in the perioperative period are dexamethasone, ondansetron and droperidol. There are general strategies that can be used to reduce the baseline surgical risk of PONV such as avoiding general anesthesia, favoring regional anesthesia, using propofol for induction and maintenance of general anesthesia, avoiding the use of nitrous oxide and/or inhalational anesthetics, minimizing the postoperative use of systemic opioids and to receive an abundant intravenous hydration during surgery. The etiology of PONV is multifactorial, so prevention and treatment should include different classes of antiemetics, acting on the different receptors of nausea and/or vomiting so far known, together with the general strategies mentioned above.

GM1 ganglioside counteracts selective neurotoxin-induced lesion of developing serotonin neurons in rat spinal cord.

The effect of exogenous monosialoganglioside GM1 on neurotoxin-induced lesioning of bulbo-spinal serotonergic neurons of newborn rats was studied by means of biochemical and immunocytochemical techniques. 5,7-dihydroxytryptamine (5,7-HT, a selective serotonin neurotoxin) treatment of newborn rats caused a pronounced reduction of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the thoracic and lumbar spinal cord, while an increase of 5-HT and 5-HIAA was found in the pons medulla. These biochemical alterations were regionally correlated with similar changes in 5-HT nerve terminal density analyzed by image analysis. GM1 administration (30 mg/kg for 4 consecutive days) antagonized the reduction of 5-HT and 5-HIAA levels induced by 5,7-HT treatment in the lumbar spinal cord of 2-month-old rats, as well as the decrease of 5-HT nerve terminal density in both thoracic and lumbar spinal cord of 1- and 2-month-old rats. A minor counteracting effect of GM1 was found in the pons medulla where the neurotoxin induced an increase of 5-HT and 5-HIAA levels. These data support the hypothesis that GM1 may have a preventing action on retrograde degenerative processes following chemical lesion and/or a growth-stimulating effect on injured 5-HT neurons.

Effect of GM1 ganglioside on neonatally neurotoxin induced degeneration of serotonin neurons in the rat brain.

The effect of exogenous GM1 ganglioside on the 5,7-dihydroxytryptamine (5,7-HT; a selective serotonin neurotoxin) induced alteration of the postnatal development of central 5-hydroxytryptamine (5-HT; serotonin) neurons has been investigated using neuro-chemical and immunocytochemical techniques. Neonatal 5,7-HT (50 mg/kg s.c.) treatment is known to lead to a marked and a permanent degeneration of distant 5-HT nerve terminal projections (e.g. in cerebral cortex, hippocampus and spinal cord), while projections close to the 5-HT perikarya in the mesencephalon and pons-medulla increase their nerve density. These regional alterations are reflected by decreases and increases, respectively, of endogenous 5-HT, [3H]5-HT uptake in vitro and number of 5-HT nerve terminals demonstrated by immunocytochemistry. Treatment of newborn rats with GM1 (4 X 30 mg/kg s.c.; 24 h interval) had no significant effect on the postnatal development of 5-HT neurons. GM1 administration had furthermore no effect on the 5,7-HT induced alteration of the regional 5-HT levels and [3H]5-HT uptake in the cerebral cortex acutely, indicating that GM1 did not significantly interfere with the primary neurodegenerative actions of 5,7-HT. At the age of 1 month a clear counteracting effect of GM1 was observed, in particular of the 5,7-HT induced 5-HT denervations. The 5-HT levels in the frontal and occipital cortex were reduced to 25 and 20% of control after 5,7-HT alone, while these values were 70 and 40%, respectively, after 5,7-HT and GM1 treatment. A similar antagonizing effect of GM1 was found in the frontal cortex when measuring [3H]5-HT uptake. GM1 treatment also caused a minor reduction of the 5,7-HT induced increase of the 5-HT levels in striatum and mesencephalon. Quantitation of 5-HT nerve terminal density in sections processed for 5-HT immunocytochemistry using an automatic image analysis system showed markedly more nerve terminals in the frontal and occipital cortex after 5,7-HT + GM1 compared to 5,7-HT treatment alone. Minor counteracting effects of GM1 were noted in the hippocampus and spinal cord (thoracic-lumbar) as evaluated by chemical 5-HT assay, although substantial counteracting effects were observed locally in these areas by quantitative immunocytochemistry.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of 5,7-dihydroxytryptamine-induced supersensitivity to 5-hydroxytryptophan in mice by treatment with cycloheximide.

Intracisternal injection of 5,7-dihydroxytryptamine (5,7-DHT) following treatment with desmethylimipramine induced development of behavioral supersensitivity to the intraperitoneally administered serotonin precursor 5-hydroxytryptophan (5-HTP) in the mouse. This behavioral syndrome, characterized by tremor and muscle twitches (myoclonus), showed a clear dose-response relationship with 5,7-DHT as well as with 5-HTP. Mice lesioned with a low dose of 5,7-DHT (20 micrograms) or a placebo were treated repeatedly with a protein synthesis inhibitor, sycloheximide (45 mg/kg, s.c., every 12 h for up to 10 days). This treatment resulted in a reversible decrease of cerebral protein synthesis varying between 70 and 20% with time between treatments. The myoclonic response to 5-HTP in animals pretreated with 5,7-DHT and by cycloheximide showed a decrease in intensity within 24 h when evaluated quantitatively by an electronic activity monitor, the results of which were confirmed by direct observation. Cycloheximide also exerted a similar, though smaller, effect following full development of sensitivity to 5-HTP over 10 days. These effects may de mediated by inhibition of rapidly turning over serotonin receptor proteins, although their interpretation is somewhat obscured by possible toxic effects of cycloheximide.