Higienização das mãos em unidades de terapia intensiva neonatal, pediátrica e adulto / Hand hygiene in neonatal, pediatric and adult intensive care units

Objetivo: Avaliar a efetividade de um programa educativo multimodal de higienização das mãos para profissionais da saúde de UTIs Neonatal, Pediátrica e Adulto. Método: Trata-se de uma pesquisa quasi-experimental, do tipo série temporal interrompida com um grupo e, portanto, esse foi avaliado antes e após a intervenção. A coleta de dados foi realizada em três períodos: (1) período pré-intervenção, realizada em 2017, observada a adesão à higienização das mãos pelos profissionais de saúde e identificado o consumo de álcool gel; (2) período de intervenção, realizada durante o ano de 2018, no qual foi executado o programa educativo multimodal; (3) período pós-intervenção, no qual foi realizada nova investigação utilizando a mesma metodologia empregada no primeiro período desta pesquisa. Resultados: Foram observadas 640 oportunidades e 327 ações, resultando assim em uma adesão global de 51,09%. O consumo de álcool em gel em 2018 obteve uma média de 27,01 mL/paciente-dia dentro das unidades e no ano de 2017 foi de 43,13 mL/paciente-dia no mesmo período. Conclusão: Apesar do período de intervenção ter ajudado os profissionais a esclarecerem dúvidas, esse ainda se mostrou não ser suficiente para manter os índices encontrados no período pré-intervenção. Pode-se sugerir que medidas educativas que promovam o aumento da adesão à higienização das mãos sejam rotineiramente realizadas. [au]

Objective: To assess the health of a multimodal hand hygiene educational program for Neonatal, Pediatric and Adult health professionals. Method: This is a quasi-experimental research, of the time series type with a group, therefore, the same group was evaluated before and after an intervention. The collection of this study was carried out in three periods: (1) pre-intervention period, carried out in 2017, observing the ingestion of hand hygiene by health professionals and identifying the gel; (2) intervention, carried out during 2018, where the multimodal educational program was implemented; (3) post-intervention period, where a new investigation was carried out using the same methodology used in the first period of this research. Results: 640 opportunities were observed and 327 actions were observed, thus resulting in an overall adherence of 1.09%. The consumption of gel alcohol in 2018 had an average of 27.01 mL/patient-day within the units and in 2017 it was 43.13 mL/patient-day in the same period. Conclusion: Although the intervention helped professionals with doubts, it still proved not to be sufficient for the rates found in the pre-vention period, it can be suggested that educational measures will maintain the increase in the extension of hand hygiene to be routinely performed. [au]

Effects of the adjunctive treatment of antidepressants with opiorphin on a panic-like defensive response in rats.

BACKGROUND: Antidepressants are the first-choice for pharmacological treatment of panic disorder. However, they present disadvantages, such as delayed therapeutic effect, many side effects and a considerable rate of non-responders. These shortcomings prompt the development of new therapeutic strategies. Among these are the adjunctive use of enkephalinase inhibitors, such as opiorphin, which supposedly acts by increasing the availability of brain enkephalins and other endogenous opioids. AIMS: We here evaluated whether opiorphin in the dorsal periaqueductal grey matter (dPAG), a key panic-related area, accelerates and/or facilitates the antipanic-like effect of fluoxetine or imipramine. We also verified whether the panicolytic effect of imipramine depends on activation of µ-opioid receptors (MORs). METHODS: Male Wistar rats were submitted to the escape task of the elevated T-maze, an index of panic attack, after treatment with imipramine (3, 7 or 21 days) or fluoxetine (3, 7, 14 or 21 days), combined with an intra-dPAG injection of opiorphin. RESULTS: Opiorphin facilitated and accelerated the panicolytic-like effect caused by imipramine, but not with fluoxetine. The antipanic-like effect caused by chronic imipramine did not depend on MOR activation in the dPAG. CONCLUSION: Combined treatment of antidepressant drugs with opiorphin for hastening or potentiating the effects of the former compounds may not be generally effective, with the results varying depending on the type/class of these panicolytic drugs.

The Blockade of µ1- and κ-Opioid Receptors in the Inferior Colliculus Decreases the Expression of Panic Attack-Like Behaviours Induced by Chemical Stimulation of the Dorsal Midbrain.

BACKGROUND: Gamma-aminobutyric acid (GABA)ergic and opioid systems play a crucial role in the neural modulation of innate fear organised by the inferior colliculus (IC). In addition, the IC is rich in GABAergic fibres and opioid neurons, which are also connected to other mesencephalic structures, such as the superior colliculus and the substantia nigra. However, the contribution of distinct opioid receptors (ORs) in the IC during the elaboration and expression of innate fear and panic-like responses is unclear. The purpose of the present work was to investigate a possible integrated action exerted by ORs and the GABAA receptor-mediated system in the IC on panic-like responses. METHODS: The effect of the blockade of either µ1- or κ-ORs in the IC was evaluated in the unconditioned fear-induced responses elicited by GABAA antagonism with bicuculline. Microinjections of naloxonazine, a µ1-OR antagonist, or nor-binaltorphimine (nor-BNI), a κ-OR antagonist, were made into the IC, followed by intramesencephalic administration of the GABAA-receptor antagonist bicuculline. The defensive behaviours elicited by the treatments in the IC were quantitatively analysed, recording the number of escapes expressed as running (crossing), jumps, and rotations, over a 30-min period in a circular arena. The exploratory behaviour of rearing was also recorded. RESULTS: GABAA-receptor blockade with bicuculline in the IC increased defensive behaviours. However, pretreatment of the IC with higher doses (5 µg) of naloxonazine or nor-BNI followed by bicuculline resulted in a significant decrease in unconditioned fear-induced responses. CONCLUSIONS: These findings suggest a role played by µ1- and κ-OR-containing connexions and GABAA receptor-mediated neurotransmission on the organisation of panic attack-related responses elaborated by the IC neurons.

µ-Opioid and 5-HT1A receptors in the dorsomedial hypothalamus interact for the regulation of panic-related defensive responses.

The dorsomedial hypothalamus (DMH) and the dorsal periaqueductal gray (DPAG) have been implicated in the genesis and regulation of panic-related defensive behaviors, such as escape. Previous results point to an interaction between serotonergic and opioidergic systems within the DPAG to inhibit escape, involving µ-opioid and 5-HT1A receptors (5-HT1AR). In the present study we explore this interaction in the DMH, using escape elicited by electrical stimulation of this area as a panic attack index. The obtained results show that intra-DMH administration of the non-selective opioid receptor antagonist naloxone (0.5 nmol) prevented the panicolytic-like effect of a local injection of serotonin (20 nmol). Pretreatment with the selective µ-opioid receptor (MOR) antagonist CTOP (1 nmol) blocked the panicolytic-like effect of the 5-HT1AR agonist 8-OHDPAT (8 nmol). Intra-DMH injection of the selective MOR agonist DAMGO (0.3 nmol) also inhibited escape behavior, and a previous injection of the 5-HT1AR antagonist WAY-100635 (0.37 nmol) counteracted this panicolytic-like effect. These results offer the first evidence that serotonergic and opioidergic systems work together within the DMH to inhibit panic-like behavior through an interaction between µ-opioid and 5-HT1A receptors, as previously described in the DPAG.

Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI.

Panic patients may have abnormalities in serotonergic and opioidergic neurotransmission. The dorsal periaqueductal gray (dPAG) plays an important role in organizing proximal defense, related to panic attacks. The 5-HT1A receptor (5-HT1A-R) is involved in regulating escape behavior that is organized in the dPAG. Activation of κ-opioid receptor (KOR) in this region causes anxiogenic effects. In this study, we investigated the involvement of KOR in regulating escape behavior, using systemic and intra-dPAG injection of the KOR antagonist Nor-BNI. As panic models, we used the elevated T-maze (ETM) and the dPAG electrical stimulation test (EST). We also evaluated whether activation of the 5-HT1A-R or the µ-opioid receptor (MOR) in the dPAG contributes to the Nor-BNI effects. The results showed that systemic administration of Nor-BNI, either subcutaneously (2.0 and 4.0mg/kg) or intraperitoneally (2.0mg/kg), impaired escape in the EST, indicating a panicolytic-like effect. Intra-dPAG injection of this antagonist (6.8nmol) caused the same effect in the EST and in the ETM. Association of ineffective doses of Nor-BNI and the 5-HT1A-R agonist 8-OH-DPAT caused panicolytic-like effect in these two tests. Previous administration of the 5-HT1A-R antagonist WAY-100635, but not of the MOR antagonist CTOP, blocked the panicolytic-like effect of Nor-BNI. These results indicate that KOR enhances proximal defense in the dPAG through 5-HT1A-R modulation, independently of MOR. Because former results indicate that the 5-HT1A-R is involved in the antipanic action of antidepressants, KOR antagonists may be useful as adjunctive or alternative drug treatment of panic disorder.

Panicolytic-like effect of tramadol is mediated by opioid receptors in the dorsal periaqueductal grey.

Tramadol is a synthetic opioid prescribed for the treatment of moderate to severe pain, acting as agonist of µ-opioid receptors and serotonin (5-HT) and noradrenaline (NE) reuptake inhibitor. This study evaluated the effects of tramadol in rats submitted to the elevated T-maze (ETM), an animal model that evaluates behavioural parameters such as anxiety and panic. Male Wistar rats were intraperitoneally (i.p.) treated acutely with tramadol (16 and 32mg/kg) and were submitted to the ETM. Tramadol (32mg/kg) promoted a panicolytic-like effect. Considering that dorsal periaqueductal grey (dPAG) is the main brain structure related to the pathophysiology of panic disorder (PD), this study also evaluated the participation of 5-HT and opioid receptors located in the dPAG in the panicolytic-like effect of tramadol. Seven days after stereotaxic surgery for implantation of a cannula in the dPAG, the animals were submitted to the test. To assess the involvement of 5-HT1A receptors on the effect of tramadol, we combined the 5-HT1A receptor antagonist, WAY100635 (0.37nmol), microinjected intra-dPAG, 10min prior to the administration of tramadol (32mg/kg, i.p.). WAY100635 did not block the panicolytic-like effect of tramadol. We also associated the non-selective opioid receptor antagonist, naloxone, systemically (1mg/kg, i.p.) or intra-dPAG (0.5nmol) administered 10min prior to tramadol (32mg/kg, i.p.). Naloxone blocked the panicolytic-like effect of tramadol in both routes of administrations, showing that tramadol modulates acute panic defensive behaviours through its interaction with opioid receptors located in the dPAG.

5-Hydroxytryptamine 1A receptors in the dorsomedial hypothalamus connected to dorsal raphe nucleus inputs modulate defensive behaviours and mediate innate fear-induced antinociception.

The dorsal raphe nucleus (DRN) is an important brainstem source of 5-hydroxytryptamine (5-HT), and 5-HT plays a key role in the regulation of panic attacks. The aim of the present study was to determine whether 5-HT1A receptor-containing neurons in the medial hypothalamus (MH) receive neural projections from DRN and to then determine the role of this neural substrate in defensive responses. The neurotracer biotinylated dextran amine (BDA) was iontophoretically microinjected into the DRN, and immunohistochemical approaches were then used to identify 5HT1A receptor-labelled neurons in the MH. Moreover, the effects of pre-treatment of the dorsomedial hypothalamus (DMH) with 8-OH-DPAT and WAY-100635, a 5-HT1A receptor agonist and antagonist, respectively, followed by local microinjections of bicuculline, a GABAA receptor antagonist, were investigated. We found that there are many projections from the DRN to the perifornical lateral hypothalamus (PeFLH) but also to DMH and ventromedial (VMH) nuclei, reaching 5HT1A receptor-labelled perikarya. DMH GABAA receptor blockade elicited defensive responses that were followed by antinociception. DMH treatment with 8-OH-DPAT decreased escape responses, which strongly suggests that the 5-HT1A receptor modulates the defensive responses. However, DMH treatment with WAY-100635 failed to alter bicuculline-induced defensive responses, suggesting that 5-HT exerts a phasic influence on 5-HT1A DMH neurons. The activation of the inhibitory 5-HT1A receptor had no effect on antinociception. However, blockade of the 5-HT1A receptor decreased fear-induced antinociception. The present data suggest that the ascending pathways from the DRN to the DMH modulate panic-like defensive behaviours and mediate antinociceptive phenomenon by recruiting 5-HT1A receptor in the MH.

Pharmacological evidence for the mediation of the panicolytic effect of fluoxetine by dorsal periaqueductal gray matter µ-opioid receptors.

Previously reported results have shown that the inhibitory effect of fluoxetine on escape behavior, interpreted as a panicolytic-like effect, is blocked by pretreatment with either the opioid receptor antagonist naloxone or the 5-HT1A receptor (5-HT1A-R) antagonist WAY100635 via injection into the dorsal periaqueductal gray matter (dPAG). Additionally, reported evidence indicates that the µ-opioid receptor (MOR) interacts with the 5-HT1A-R in the dPAG. In the present work, pretreatment of the dPAG with the selective MOR blocker CTOP antagonized the anti-escape effect of chronic fluoxetine (10 mg/kg, i.p., daily, for 21 days), as measured in the elevated T-maze (ETM) test, indicating mediation of this effect by the MOR. In addition, the combined administration of sub-effective doses of the selective MOR agonist DAMGO (intra-dPAG) and sub-effective doses of chronic as well as subchronic (7 days) fluoxetine increased avoidance and escape latencies, suggesting that the activation of MORs may facilitate and accelerate the effects of fluoxetine. The current observation that MORs located in the dPAG mediate the anti-escape effect of fluoxetine may open new perspectives for the development of more efficient and fast-acting panic-alleviating drugs.

Anxiolytic effects of a semipurified constituent of guaraná seeds on rats in the elevated T-maze test.

The objective of this study was to investigate the effects of chronic administration of a semi-purified extract (Purified Extract A--PEA; 4, 8, or 16 mg/kg) of PAULLINIA CUPANA (guaraná) seeds on rats submitted to the elevated T-maze (ETM) model of generalized anxiety and panic disorders. The selective serotonin (5-HT) reuptake inhibitor (SSRI) paroxetine (PAR; 3 mg/kg), was used as a positive control. To evaluate possible serotonergic and dopaminergic neurotransmission involvement in the action of PEA during the ETM test, ineffective doses of metergoline (MET; 5-HT (2A/2C) antagonist receptor) or sulpiride (SUL; dopaminergic receptor antagonist) were acutely administered together with the PEA. The locomotion of the rats was assessed in a circular arena following each drug treatment. Both PEA (8 and 16 mg/kg) and PAR (3 mg/kg) increased one-way escape latencies from the open arm of the ETM, indicating a panicolytic effect compared to the control group. MET, in higher doses (1, 2 or 3 mg/kg), produced a panicolytic effect in the ETM test, whereas SUL did not (10, 20 or 40 mg/kg). The panicolytic effect produced by PEA (8 mg/kg) was blocked by both MET (2 mg/kg) and SUL (20 mg/kg), whereas the panicolytic effect produced by PAR (3 mg/kg) was blocked only by MET (2 mg/kg). These results show that chronic treatment with PEA produces a panicolytic effect during the ETM test, and that the dopaminergic and the serotonergic neurotransmission systems are involved in this effect.