Manejo perioperatorio en cirugía torácica / Perioperative management in thoracic surgery

La cirugía torácica ha experimentado importantes avances en los últimos años relacionados con las técnicas anestésicas y quirúrgicas y la prevención y el manejo de las complicaciones relacionadas con el procedimiento. Esto ha permitido mejorar los resultados clínicos de los pacientes sometidos a este tipo de intervención. A pesar de ello, los procedimientos de cirugía torácica, especialmente los relacionados con la resección pulmonar, no están exentos de riesgo, con una morbimortalidad asociada considerable. Los protocolos Fast track o Enhanced recovery after anesthesia, la cirugía mínimamente invasiva y el manejo anestésico intraoperatorio mejoran el pronóstico y la seguridad de los procesos de cirugía torácica. Los pacientes postoperados de cirugía torácica mayor requieren una vigilancia intensiva, especialmente las primeras 24-72 h del postoperatorio inmediato. El ingreso en la UCI se recomienda especialmente en los pacientes con comorbilidad, con reserva cardiopulmonar reducida, con resecciones pulmonares extensas y en los que requieren soporte por fallo de algún órgano con riesgo vital. Durante el periodo postoperatorio la monitorización intensiva cardiorrespiratoria, el manejo adecuado de los drenajes torácicos, el control agresivo del dolor (analgesia multimodal y técnicas anestésicas regionales), las náuseas y la rehabilitación multimodal son elementos claves para evitar eventos adversos. Entre las complicaciones médicas destacan la insuficiencia respiratoria, las arritmias, las infecciones respiratorias, las atelectasias y la enfermedad pulmonar tromboembólica. Las complicaciones quirúrgicas más frecuentes son el hemotórax, el quilotórax, la fístula broncopleural y la fuga aérea prolongada. El manejo multidisciplinar de estos pacientes durante todo el periodo perioperatorio es esencial para asegurar los mejores resultados quirúrgicos

Thoracic surgery has undergone significant advances in recent years related to anesthetic and surgical techniques and the prevention and management of complications related to the procedure. This has allowed improvements in patient clinical outcomes in surgeries of this kind. Despite the above, thoracic surgery, especially related to pulmonary resection, is not without risk, and is associated to considerable morbidity and mortality. Fast track or enhanced recovery after anesthesia protocols, minimally invasive surgery, and intraoperative anesthetic management improve the prognosis and safety of thoracic surgery. Patients in the postoperative period of major thoracic surgery require intensive surveillance, especially the first 24-72 hours after surgery. Admission to the ICU is especially recommended in those patients with comorbidities, a reduced cardiopulmonary reserve, extensive lung resections, and those requiring support due to life-threatening organ failure. During the postoperative period, intensive cardiorespiratory monitoring, proper management of thoracic drainage, aggressive pain control (multimodal analgesia and regional anesthetic techniques), nausea and multimodal rehabilitation are key elements for avoiding adverse events. Medical complications include respiratory failure, arrhythmias, respiratory infections, atelectasis and thromboembolic lung disease. The most frequent surgical complications are hemothorax, chylothorax, bronchopleural fistula and prolonged air leakage. The multidisciplinary management of these patients throughout the perioperative period is essential in order to ensure the best surgical outcomes

Perioperative management in thoracic surgery. / Manejo perioperatorio en cirugía torácica.

Thoracic surgery has undergone significant advances in recent years related to anesthetic and surgical techniques and the prevention and management of complications related to the procedure. This has allowed improvements in patient clinical outcomes in surgeries of this kind. Despite the above, thoracic surgery, especially related to pulmonary resection, is not without risk, and is associated to considerable morbidity and mortality. Fast track or enhanced recovery after anesthesia protocols, minimally invasive surgery, and intraoperative anesthetic management improve the prognosis and safety of thoracic surgery. Patients in the postoperative period of major thoracic surgery require intensive surveillance, especially the first 24-72hours after surgery. Admission to the ICU is especially recommended in those patients with comorbidities, a reduced cardiopulmonary reserve, extensive lung resections, and those requiring support due to life-threatening organ failure. During the postoperative period, intensive cardiorespiratory monitoring, proper management of thoracic drainage, aggressive pain control (multimodal analgesia and regional anesthetic techniques), nausea and multimodal rehabilitation are key elements for avoiding adverse events. Medical complications include respiratory failure, arrhythmias, respiratory infections, atelectasis and thromboembolic lung disease. The most frequent surgical complications are hemothorax, chylothorax, bronchopleural fistula and prolonged air leakage. The multidisciplinary management of these patients throughout the perioperative period is essential in order to ensure the best surgical outcomes.

A new severe mutation in the SLC5A7 gene related to congenital myasthenic syndrome type 20.

Congenital myasthenic syndromes are a group of genetically determined rare diseases resulting from ultrastructural alterations in synaptic proteins. Up to 32 genes are known to be involved in those syndromes and many mutations have been reported, of which less than 8% affect the presynaptic complex. One of these syndromes is caused by the impairment of the presynaptic sodium-dependent high-affinity choline transporter 1, as a result of a mutation of the SCL5A7 gene associated with congenital myasthenic syndrome type 20 (MIM # 617143). We present a new case of this syndrome, caused by a mutation not previously described. A full term infant presented with acute respiratory failure and generalized weakness. The genetic analysis revealed the patient to be compound heterozygous for a new mutation of the SCL5A7 gene. The genetic analysis of congenital myasthenic syndromes provide information on the ultrastructural underlying mechanisms, which is valuable for differential diagnosis and specific treatments.

Inhibitory synaptogenesis in the rat anteroventral cochlear nucleus.

Spherical cells in the anteroventral division of the cochlear nucleus, which relay excitatory inputs from the auditory nerve, also receive both GABAergic and glycinergic inhibitory synapses. Inhibition mediated by GABA and glycine fulfils essential roles in the processing abilities of these and other auditory neurons. However, the developmental program leading to a mature complement of GABAergic and glycinergic synapses and microcircuits is largely unknown. Because of their relatively simple geometry, spherical cells provide an excellent model for unraveling basic developmental patterns of inhibitory synaptogenesis. Using a combination of high resolution immunocytochemical methods, we report that, in the rat, synapses containing GABA or glycine are deployed on spherical cell bodies over a time period extending well beyond hearing onset. Such postnatal developmental recruitment of inhibitory endings is progressive, although there are two distinct leaps in their numbers. The first occurs by the end of the first postnatal week, prior to hearing onset, and the second, during the third postnatal week, after hearing onset. This pattern suggests that adjustments in inhibition could be driven by acoustic experience. While GABAergic and glycinergic endings are maturing and growing in number and size, their neurotransmitter content also appears to be developmentally regulated. Quantitative ultrastructural immunocytochemistry with colloidal gold suggests that GABA and glycine accumulation in synaptic endings follows a staggered pattern, with labeling stabilizing at adult levels by postnatal day 21. This may account for adjustments in synaptic efficacy and strength.

The calcium-binding protein calretinin is a marker of the companion cell layer of the human hair follicle.

BACKGROUND: Ultrastructural studies of the hair follicle show that the outer root sheath (ORS) does not consist of a homogeneous cell population. The innermost cell layer of the ORS, also called the companion layer, is a single cell layer closely associated with the Henle layer of the inner root sheath. OBJECTIVES: To describe the immunohistochemical expression of calretinin, a calcium-binding protein, in the human hair follicle. METHODS: Immunohistochemical studies using two different antisera to calretinin were performed in paraffin-embedded and in frozen scalp specimens using standard techniques. RESULTS: Calretinin immunostaining was consistently and specifically found in the companion cell layer of hair follicles. CONCLUSIONS: These findings provide further evidence to support the notion that the companion layer is not only morphologically, but also immunohistochemically, different from the other cells of the ORS.

Expression of GABA(A) receptor subunits in rat brainstem auditory pathways: cochlear nuclei, superior olivary complex and nucleus of the lateral lemniscus.

Inhibition by GABA is important for auditory processing, but any adaptations of the ionotropic type A receptors are unknown. Here we describe, using in situ hybridization, the subunit expression patterns of GABA(A) receptors in the rat cochlear nucleus, superior olivary complex, and dorsal and ventral nuclei of the lateral lemniscus. All neurons express the beta3 and gamma2L subunit messenger RNAs, but use different alpha subunits. In the dorsal cochlear nucleus, fusiform (pyramidal) and giant cells express alpha1, alpha3, beta3 and gamma2L. Dorsal cochlear nucleus interneurons, particularly vertical or tuberculoventral cells and cartwheel cells, express alpha3, beta3 and gamma2L. In the ventral cochlear nucleus, octopus cells express alpha1, beta3, gamma2L and delta. Spherical cells express alpha1, alpha3, alpha5, beta3 and gamma2L. In the superior olivary complex, the expression profile is alpha3, alpha5, beta3 and gamma2L. Both dorsal and ventral cochlear nucleus granule cells express alpha1, alpha6, beta3 and gamma2L; unlike their cerebellar granule cell counterparts, they do not express beta2, gamma2S or the delta subunit genes. The delta subunit's absence from cochlear nucleus granule cells may mean that tonic inhibition mediated by extrasynaptic GABA(A) receptors is less important for this cell type. In both the dorsal and ventral nuclei of the lateral lemniscus, alpha1, beta3 and gamma2L are the main subunit messenger RNAs; the ventral nucleus also expresses the delta subunit. We have mapped, using in situ hybridization, the subunit expression patterns of the GABA(A) receptor in the auditory brainstem nuclei. In contrast to many brain regions, the beta2 subunit gene and gamma2S splice forms are not highly expressed in auditory brainstem nuclei. GABA(A) receptors containing beta3 and gamma2L may be particularly well suited to auditory processing, possibly because of the unique phosphorylation profile of this subunit combination.

The expression of behavioral sensitization to amphetamine: role of CCK(A) receptors.

These studies investigated whether endogenous activation of CCK(A) receptors mediates the expression of amphetamine (AMP)-induced locomotor activity. In Experiment 1, locomotor activity was assessed in rats pretreated with the CCK(A) antagonist devazepide (0.001, 0.01, and 0.1 mg/kg) and subsequently injected with AMP (1.5 mg/kg). In Experiment 2, rats were administered AMP (1.5 mg/kg) once daily for 7 days. Following a 10-day withdrawal, locomotor activity was assessed following treatment with devazepide (0.001, 0.01, and 0.1 mg/kg) and AMP (0.75 mg/kg). In both studies, rats were classified as low (LR) or high (HR) responders based upon a median split of their locomotor response to a novel environment. Results from Experiment 1 showed that AMP potentiated the expression of locomotor activity, and this effect was most pronounced in HR rats. However, devazepide did not affect AMP-induced locomotion. Results from Experiment 2 demonstrated that chronic AMP pretreatment augmented the locomotor response to subsequent AMP challenge, and this effect was most pronounced in the HR group. Further, this augmented response was blocked by devazepide in HR rats. These findings constitute the first demonstration that endogenous CCK(A) receptor activation is an important substrate mediating AMP-induced locomotor activity in animals with a previous history of AMP treatment.

Individual differences in sucrose intake predict behavioral reactivity in rodent models of anxiety.

We have previously shown that individual differences in oral sucrose consumption are predictive of behavioral reactivity of rats in the elevated plus-maze (EPM). The present experiments were designed to replicate the EPM results and to extend them to another animal model of anxiety, the acoustic startle reflex (ASR) paradigm. In two experiments, sucrose consumption was assessed in separate groups of rats across eight daily 1-h feeding sessions. Animals were designated as either low (LSF) or high sucrose feeders (HSF) based on a median split of their sucrose intake on the final test day. Following this assay, animals were tested in the EPM in Experiment 1, and in the ASR paradigm in Experiment 2. Results from Experiment 1 replicated our previous findings and showed that the percentage of time spent on, and entries into, open arms was significantly lower in LSF than HSF. Further, results from Experiment 2 revealed a significantly augmented startle response to acoustic stimuli (94-108 dB SPL) in LSF compared to HSF. These data provide converging evidence to support the notion that individual differences in baseline levels of oral sucrose consumption are predictive of anxious behaviors in rats.

Cholecystokinergic innervation of nucleus accumbens subregions.

Behavioral and pharmacological evidence has shown a different and opposite role of the neuropeptide cholecystokinin (CCK) on the dopamine (DA) function in the caudal versus rostral part of the nucleus accumbens. Previous reports have speculated that the caudal region of the nucleus accumbens would receive CCKergic innervation from dopaminergic neurons of the mesencephalic ventral tegmental area, whereas the CCKergic input to the rostral accumbens would originate in non-dopaminergic neurons from extra-mesencephalic areas of the brain. In the present study, this issue was addressed using retrograde tracing techniques in conjunction with immunocytochemistry. Retrograde tracers were injected in the three compartments of the accumbens (i.e., rostral pole, core and septal shell). In summary, our results demonstrate that 1) the main CCKergic input of the accumbens originates in the ventral mesencephalon; 2) the rostral pole is equally innervated by CCK neurons projecting from both substantia nigra pars compacta and ventral tegmental area; 3) the primary source of CCK innervation of the accumbal core is the substantia nigra pars compacta; and 4) whereas the CCKergic input to the septal shell originates primarily in the ventral tegmental area. Additionally, our results also showed that most of the CCKergic neurons projecting to any of the accumbal compartments also produce dopamine. These data constitute the first neuroanatomical evidence for the differential effects of CCK on dopamine actions in the different regions of the nucleus accumbens.

Effects of neonatal naltrexone on neurological and somatic development in rats of both genders.

The effects of a daily injection of the opioid antagonist naltrexone (NALTX, 1 mg/kg, s.c.) from birth to weaning on various parameters were investigated in male and female rats during postnatal development until adulthood. NALTX increased cerebellar DNA and protein content as well as cerebellar weight at 7 days. Eye opening was not affected by NALTX but it appeared advanced by 1 day in all groups compared to other studies, possibly due to a handling effect caused by the daily injection. Water and food consumption were augmented by NALTX during days 23-32 and days 55-70. Treated preweaning animals showed lower body growth rates than controls. However, NALTX caused a moderate increase in body weight measured during postweaning until adulthood. The effects of NALTX on the parameters evaluated (excepting the cerebellar measurements on day 7), although clearly statistically significant, were small in absolute terms. The preweaning opioid blockade caused by our NALTX treatment seems to affect more markedly the neural and behavioural development than the somatic growth. This work also provides potentially useful baseline data for the study of male and female rats during postnatal development.

Naltrexone administration during the preweanling period affects striatal and hypothalamic serotonergic systems, but not midbrain serotonergic or striatal dopaminergic systems in the adult rat.

We have recently reported that daily administration from birth of the opioid antagonist naltrexone (1 mg/kg, s.c.) affected dopaminergic and serotonergic systems in the striatum, hypothalamus and midbrain in rats of 7, 14 and 22 days of age. Previously, we have also reported that the same dose of naltrexone administered from birth until day 21 caused diverse behavioural alterations in adulthood. In the present work, using the same naltrexone administration schedule, we demonstrate that the intermittent blockade of opioid receptors during preweanling period induces significant decreases in striatal 5-hydroxytryptamine (5-HT) and 5-hydroxy-3-indoleacetic acid (5-HIAA) concentrations, and a significant reduction of hypothalamic 5-HT levels in the adult rat. However, no effects were found on midbrain serotonergic or striatal dopaminergic systems. These results are discussed in terms of possible different sensitivities of the diverse monoaminergic systems to the naltrexone treatment. Possible correlations with the behavioural data reported previously are also suggested.

Naltrexone administration effects on regional brain monoamines in developing rats.

The effects of the opioid antagonist naltrexone (NALTX) daily administration (1 mg/kg SC) from birth on the levels of dopamine (DA), serotonin (5-HT), and their respective major metabolites, in the striatum, midbrain, and hypothalamus of 7-, 14-, and 22-day-old rats were investigated. Naltrexone treatment increased the striatal HVA/DA ratio on postnatal day 7. At day 14, two subpopulations (A and B) were found among the treated animals. The subpopulation A showed decreased HVA/DA and increased DOPAC/DA ratios, whereas the subpopulation B presented a higher DA concentration. No significant effect appeared on the striatal dopaminergic system in 22-day-old pups. The serotonergic system was affected by exposure to naltrexone only from day 14. The subpopulation A showed a reduction in all the parameters measured in the three regions studied, although in the subpopulation B, lower 5-HIAA/5-HT ratios appeared in the midbrain and hypothalamus. At 22 days of age NALTX treatment elevated striatal 5-HT and 5-HIAA and the ratio of 5-HIAA/5-HT in the midbrain and hypothalamus. These data suggest an endogenous opioid modulation on the central aminergic systems during the neonatal period and point out the consequences of opioid plasticity on related neurotransmitter systems.

A developmental study on stress-induced antinociception measured by the tail electric stimulation test.

The possible influence of weaning on the development of different neural mechanisms involved in stress-induced antinociception (SIA) was studied. Male Wistar albino rats were used for studies on adult and pre- and postweanling rats of 20 and 25 days of age, respectively. Animals were stressed by warm-water (20C) swimming for 3-min periods. Antinociception was assessed by the tail electric stimulation test. The thresholds for the motor response (tail withdrawal) (TW), vocalization during stimulus (V), and vocalization after discharge (VAD) were recorded. These responses are considered to be integrated at spinal, medulla oblongata, and diencephalon-rhinencephalon levels, respectively. In 20-day-old neonates, swimming stress only induced significant increases in the VAD thresholds that were not significantly reversed by naloxone (NAL) (1 mg/kg). Twenty-five-day-old rats showed increased threshold for the three nociceptive responses after stress, the effects on TW and V being antagonized by NAL. Adult rats subjected to stress showed increased threshold for the three responses, an effect that was antagonized by NAL in all cases. These results suggest that the weaning period might be critical for the development of the mechanisms mediating SIA. Besides, a different involvement of opioid systems throughout development, particularly in relation to the affective/emotional component of pain, is also suggested.

A study on the development of nociceptive responses in pre- and postweanling rats: the tail electric stimulation test as a suitable methodology.

The development of nociceptive responses to the tail electric stimulation test was investigated. Male Wistar albino rats were used for studies on adult and pre- and postweanling rats of 20 and 25 days of age, respectively. The thresholds for the motor response (tail withdrawal), vocalization during stimulus and vocalization afterdischarge were assessed. These responses are considered to be integrated at spinal, medulla oblongata and diencephalon-rhinencephalon levels, respectively. Adult animals showed significantly higher thresholds for the three responses when compared to the neonates, while 25-day old rats showed significantly higher thresholds for the vocalization afterdischarge than the 20-day old pups. Although the effect of age cannot be ruled out, these latter results might indicate that the weaning process is critical in the development of the mechanisms related to the emotional/affective component of pain. The results also indicate the suitability of the nociceptive test employed for these kinds of studies.

Effects of beta-funaltrexamine treatment and sexual isolation in the perinatal period on the development of mu-opioid receptors and nociception.

Male and female rats were segregated from birth (sexually isolated animals). Additional litters containing both male and female pups were kept as controls (mixed-housed animals). beta-FNA (5 mg/kg) or water was administered SC at day 0 or day 7 to isolated and mixed-housed animals. The development of mu-opioid receptors and nociceptive responses in the two groups was assessed at day 7 or 14, respectively. Mu-receptor binding was measured in whole brain using (3H) DAGO as a binding ligand and nociception assessed using the tail immersion test. beta-FNA treatment depressed mu-receptors when measured 1 but no 7 days later. However, male and female rats treated at day 0 with beta-FNA had lower brain protein content. Sexual isolation had little effect on mu-receptor number and did not augment the beta-FNA effect. However, isolation increased pain sensitivity in 7-day-old animals and in 14-day-old females. beta-FNA treatment had little effect on nociceptive threshold but reversed the effects of sexual isolation.