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1.
J Clin Med ; 8(9)2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31540049

RESUMO

Endotracheal intubation is still the gold standard in airway management. For medical students and young professionals, it is often difficult to train personal skills. We tested a high-fidelity simulator with an additional quantitative feedback integration to elucidate if competence acquisition for airway management is increased by using this feedback method. In the prospective trial, all participants (n = 299; 4th-year medical students) were randomized into two groups-One had been trained on the simulator with additional quantitative feedback (n = 149) and one without (n = 150). Three simulator measurements were considered as quality criteria-The pressure on the upper front row of teeth, the correct pressure point of the laryngoscope spatula and the correct depth for the fixation of the tube. There were a total of three measurement time points-One after initial training (with additional capture of cognitive load), one during the exam, and a final during the follow-up, approximately 20 weeks after the initial training. Regarding the three quality criteria, there was only one significant difference, with an advantage for the control group with respect to the correct pressure point of the laryngoscope spatula at the time of the follow-up (p = 0.011). After the training session, the cognitive load was significantly higher in the intervention group (p = 0.008) and increased in both groups over time. The additional quantitative feedback of the airway management trainer brings no measurable advantage in training for endotracheal intubation. Due to the increased cognitive load during the training, simple airway management task training may be more efficient for the primary acquisition of essential procedural steps.

2.
Br J Anaesth ; 123(3): 335-349, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31303268

RESUMO

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.


Assuntos
Dor Aguda/tratamento farmacológico , Analgésicos/farmacologia , Anestésicos Locais/farmacologia , Dor Crônica/tratamento farmacológico , Lidocaína/farmacologia , Terapia de Alvo Molecular/métodos , Dor Aguda/metabolismo , Analgésicos/uso terapêutico , Anestésicos Locais/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor Crônica/metabolismo , Humanos , Canais Iônicos/efeitos dos fármacos , Lidocaína/uso terapêutico , Transmissão Sináptica/efeitos dos fármacos
3.
Lung ; 197(2): 217-226, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30739218

RESUMO

PURPOSE: Acute allograft rejection after lung transplantation remains an unsolved hurdle. The pathogenesis includes an inflammatory response during and after transplantation. Ropivacaine, an amide-linked local anesthetic, has been shown to attenuate lung injury due to its anti-inflammatory effects. We hypothesized that the drug would also be able to attenuate acute rejection (AR) after allogeneic lung transplantation. METHODS: Allogeneic, orthotopic, single left lung transplantation was performed between BALB/c (donors) and C57BL/6 (recipients) mice. Prior to explantation, lungs were flushed with normal saline with or without ropivacaine (final concentration 1 µM). Plasma levels of tumor necrosis factor-α and interleukins - 6 and - 10 were measured 3 h after transplantation by ELISA. Lung function was assessed on postoperative day five and transplanted lungs were analyzed using histology (AR), immunohistochemistry (infiltrating leukocytes) and Western blot (phosphorylation and expression of Src and caveolin-1). RESULTS: Ropivacaine pre-treatment significantly reduced AR scores (median 3 [minimum-maximum 2-4] for control vs. 2 [1-2] for ropivacaine, p < 0.001) and plasma levels of tumor necrosis factor-α (p = 0.01) compared to control, whereas plasma concentrations of interleukin - 6 (p = 0.008) and - 10 (p < 0.001) were increased by ropivacaine. The number of T-lymphocytes infiltrating the transplanted lung was attenuated (p = 0.02), while no differences in macrophage or B-lymphocyte numbers could be observed after ropivacaine pre-treatment. Caveolin-1 phosphorylation in ropivacaine-treated lungs was diminished (p = 0.004). CONCLUSIONS: Pre-treatment of donor lungs with the local anesthetic ropivacaine diminished histological signs of AR after orthotopic left lung transplantation in mice, most likely due to reduced infiltration of T-lymphocytes into the graft.


Assuntos
Anestésicos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Pulmão/efeitos adversos , Pulmão/efeitos dos fármacos , Ropivacaina/farmacologia , Doença Aguda , Aloenxertos , Animais , Caveolina 1/metabolismo , Quimiotaxia de Leucócito/efeitos dos fármacos , Citocinas/sangue , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Mediadores da Inflamação/sangue , Pulmão/imunologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fosforilação , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T/metabolismo , Fatores de Tempo
4.
BMC Anesthesiol ; 18(1): 88, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30021507

RESUMO

BACKGROUND: Due to its potential beneficial effects, intra- and postoperative application of intravenous lidocaine has become increasingly accepted over the last couple of years, e.g. in patients undergoing laparoscopic surgical procedures. Based on its beneficial properties, lidocaine was introduced to the standard of care for all pediatric laparoscopic procedures in our institution in mid-2016. In contrast to adult care, scarce data is available regarding the use of perioperative intravenous lidocaine administration in children undergoing laparoscopic procedures, such as an appendectomy. METHODS: Retrospective analysis of all pediatric patients undergoing laparoscopic appendectomy at the University Children's Hospital Zurich in 2016. Perioperative data, as recorded in the electronic patient data management system, were evaluated for any signs of systemic lidocaine toxicity (neurological and cardiovascular), behavioral deterioration, as well as for hemodynamic instability. Additionally, the incidence of postoperative nausea and vomiting, administration of pain rescue medication, time to hospital discharge and to first bowel movement, as well as any postoperative complications were recorded. Starting on 01/07/2016, all patients undergoing laparoscopic surgery received intravenous lidocaine (1.5 mg/kg body weight (BW) bolus after induction of anesthesia followed by continuous infusion of 1.5 mg/kgBW/h). These patients were then compared to children without lidocaine administration who had undergone laparoscopic appendectomy between 01/01/2016 and 30/06/2016. RESULTS: Data of 116 patients was analyzed. Of these, 60 patients received lidocaine. No signs of systemic toxicity, neurologic impairment or circulatory disturbances were noted in any of these patients. A (non-significant) difference in the incidence of emergence delirium was observed (0 cases in the lidocaine group vs. 4 cases in the control group, p = 0.05). CONCLUSION: This retrospective analysis did not reveal any adverse effects in pediatric patients receiving intravenous lidocaine for laparoscopic appendectomy under general anesthesia. However, further trials investigating beneficial effects as well as pharmacokinetic properties of intravenous lidocaine in children are required.


Assuntos
Apendicectomia/estatística & dados numéricos , Constipação Intestinal/epidemiologia , Laparoscopia/estatística & dados numéricos , Lidocaína/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Náusea e Vômito Pós-Operatórios/epidemiologia , Vômito/epidemiologia , Administração Intravenosa , Anestésicos Locais/administração & dosagem , Anestésicos Locais/efeitos adversos , Apendicectomia/métodos , Estudos de Casos e Controles , Criança , Constipação Intestinal/induzido quimicamente , Delírio/epidemiologia , Feminino , Humanos , Infusões Intravenosas , Laparoscopia/métodos , Tempo de Internação , Lidocaína/administração & dosagem , Masculino , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Estudos Retrospectivos , Suíça/epidemiologia , Fatores de Tempo , Vômito/induzido quimicamente
5.
Front Med (Lausanne) ; 4: 235, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29326939

RESUMO

Surgical removal of the primary tumor in solid cancer is an essential component of the treatment. However, the perioperative period can paradoxically lead to an increased risk of cancer recurrence. A bimodal dynamics for early-stage breast cancer recurrence suggests a tumor dormancy-based model with a mastectomy-driven acceleration of the metastatic process and a crucial role of the immunosuppressive state during the perioperative period. Recent evidence suggests that anesthesia could also influence the progress of the disease. Local anesthetics (LAs) have long been used for their properties to block nociceptive input. They also exert anti-inflammatory capacities by modulating the liberation or signal propagation of inflammatory mediators. Interestingly, LAs can reduce viability and proliferation of many cancer cells in vitro as well. Additionally, retrospective clinical trials have suggested that regional anesthesia for cancer surgery (either with or without general anesthesia) might reduce the risk of recurrence. Lidocaine, a LA, which can be administered intravenously, is widely used in clinical practice for multimodal analgesia. It is associated with a morphine-sparing effect, reduced pain scores, and in major surgery probably also with a reduced incidence of postoperative ileus and length of hospital stay. Systemic delivery might therefore be efficient to target residual disease or reach cells able to form micrometastasis. Moreover, an in vitro study has shown that lidocaine could enhance the activity of natural killer (NK) cells. Due to their ability to recognize and kill tumor cells without the requirement of prior antigen exposure, NKs are the main actor of the innate immune system. However, several perioperative factors can reduce NK activity, such as stress, pain, opioids, or general anesthetics. Intravenous lidocaine as part of the perioperative anesthesia regimen would be of major interest for clinicians, as it might bear the potential to reduce the risk of cancer recurrence or progression patients undergoing cancer surgery. As a well-known pharmaceutical agent, lidocaine might therefore be a promising candidate for oncological drug repurposing. We urgently need clinical randomized trials assessing the protective effect of lidocaine on NKs function and against recurrence after cancer surgery to achieve a "proof of concept."

6.
Anesth Analg ; 124(1): 194-203, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27782948

RESUMO

BACKGROUND: Patients experiencing acute lung injury (ALI) often need mechanical ventilation for which sedation may be required. In such patients, usually the first choice an intravenously administered drug. However, growing evidence suggests that volatile anesthetics such as sevoflurane are a valuable alternative. In this study, we evaluate pulmonary and systemic effects of long-term (24-hour) sedation with sevoflurane compared with propofol in an in vivo animal model of ALI. METHODS: Adult male Wistar rats were subjected to ALI by intratracheal lipopolysaccharide (LPS) application, mechanically ventilated and sedated for varying intervals up to 24 hours with either sevoflurane or propofol. Vital parameters were monitored, and arterial blood gases were analyzed. Inflammation was assessed by the analysis of bronchoalveolar lavage fluid (BALF), cytokines (monocyte chemoattractant protein-1 [MCP-1], cytokine-induced neutrophil chemoattractant protein-1 [CINC-1], interleukin [IL-6], IL-12/12a, transforming growth factor-ß, and IL-10) in blood and lung tissue and inflammatory cells. The alveolocapillary barrier was indirectly assessed by wet-to-dry ratio, albumin, and total protein content in BALF. Results are presented as mean ± standard deviation. RESULTS: After 9 hours of ventilation and sedation, oxygenation index was higher in the LPS/sevoflurane (LPS-S) than in the LPS/propofol group (LPS-P) and reached 400 ± 67 versus 262 ± 57 mm Hg after 24 hours (P < .001). Cell count in BALF in sevoflurane-treated animals was lower after 18 hours (P = .001) and 24 hours (P < .001) than in propofol controls. Peak values of CINC-1 and IL-6 in BALF were lower in LPS-S versus LPS-P animals (CINC-1: 2.7 ± 0.7 vs 4.0 ± 0.9 ng/mL; IL-6: 9.2 ± 2.3 vs 18.9 ± 7.1 pg/mL, both P < .001), whereas IL-10 and MCP-1 did not differ. Also messenger RNAs of CINC-1, IL-6, IL-12a, and IL-10 were significantly higher in LPS-P compared with LPS-S. MCP-1 and transforming growth factor-ß showed no differences. Wet-to-dry ratio was lower in LPS-S (5.4 ± 0.2 vs 5.7 ± 0.2, P = .016). Total protein in BALF did not differ between P-LPS and S-LPS groups. CONCLUSIONS: Long-term sedation with sevoflurane compared with propofol improves oxygenation and attenuates the inflammatory response in LPS-induced ALI. Our findings suggest that sevoflurane may improve lung function when used for sedation in patients with ALI.


Assuntos
Lesão Pulmonar Aguda/terapia , Anestésicos Inalatórios/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Pulmão/efeitos dos fármacos , Éteres Metílicos/administração & dosagem , Oxigênio/sangue , Pneumonia/prevenção & controle , Propofol/administração & dosagem , Lesão Pulmonar Aguda/sangue , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/fisiopatologia , Animais , Biomarcadores/sangue , Barreira Alveolocapilar/efeitos dos fármacos , Barreira Alveolocapilar/metabolismo , Líquido da Lavagem Broncoalveolar/química , Permeabilidade Capilar/efeitos dos fármacos , Citocinas/sangue , Citocinas/genética , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Mediadores da Inflamação/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Lipopolissacarídeos , Pulmão/metabolismo , Masculino , Pneumonia/sangue , Pneumonia/induzido quimicamente , Pneumonia/fisiopatologia , Ratos Wistar , Respiração Artificial , Sevoflurano , Fatores de Tempo
7.
Sci Rep ; 6: 34913, 2016 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-27734897

RESUMO

Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.


Assuntos
Bilirrubina/química , Muramidase/química , Peptidil Dipeptidase A/química , Animais , Anticorpos Monoclonais/química , Células CHO , Estudos de Casos e Controles , Membrana Celular/metabolismo , Cricetinae , Cricetulus , Citometria de Fluxo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Camundongos , Mutação , Peptídeos/química , Fenótipo , Ligação Proteica , Domínios Proteicos , Sarcoidose/sangue , Ressonância de Plasmônio de Superfície
9.
Oncol Lett ; 12(2): 1513-1518, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27446462

RESUMO

Circulating tumor cells (CTCs) in the blood of cancer patients have been demonstrated to be of prognostic value regarding metastasis and survival. The CellSearch® system has been certified for the detection of CTCs and as a prognostic tool in patients with metastatic breast, colon and prostate cancer. Few studies have evaluated the detection of CTCs originating from esophagogastric or pancreatic cancer with the CellSearch® system. In the present small pilot study, a total of 16 patients with either esophagogastric (n=8) or pancreatic (n=8) adenocarcinomas at various disease stages were randomly screened and included. A total of 7.5 ml of blood was drawn from each patient and analyzed for CTCs using the CellSearch® device. CTCs could be detected in 1 out of 8 patients (12.5%) with esophagogastric and in 7 out of 8 patients (87.5%) with pancreatic cancer. The preliminary data obtained from this observational feasibility study suggested that the CellSearch® system may become a valuable tool for the detection of CTCs in patients with pancreatic adenocarcinoma, whereas the usefulness in patients with early-stage esophagogastric adenocarcinoma may be limited. This study clearly points towards a requirement for larger studies focusing on patients with pancreatic adenocarcinoma at various disease stages and assessing CTCs, whereas patients with esophagogastric adenocarcinomas should be part of further pilot studies.

10.
Resuscitation ; 105: 66-9, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27241333

RESUMO

INTRODUCTION: Airway management in the out-of-hospital emergency setting is challenging. Failed and even prolonged airway management is associated with serious clinical consequences, such as desaturation, bradycardia, airway injuries, or aspiration. The overall success rate of tracheal intubation ranges between 77% and 99%, depending on the level of experience of the provider. Therefore, advanced airway management should only be performed by highly-skilled and experienced providers. METHODS: 9765 patients were treated in the out-of-hospital emergency setting by the anaesthesiologist-staffed Helicopter Emergency Medical Services (HEMS) between 2002 and 2014. Patients successfully intubated upon the first attempt were compared to patients who required more than one intubation attempts regarding several potential confounding factors such as age, gender, on-going CPR, NACA Score, initial GCS, prior administration of anaesthetic drugs, neuromuscular blocking agents, and vasopressors. RESULTS: 1573 out of 9765 patients (16.1%) required advanced airway management. 459 patients had already been intubated upon arrival of the HEMS, whereas 1114 patients (11.4%) underwent advanced airway management by the HEMS physician. 67 patients had to be excluded. Data for the remaining 1047 patients (790 males and 257 females) were analyzed further. Primary use of an alternative airway device was reported in 59 patients (5.6%), whereas 988 patients (94.4%) underwent laryngoscopy-guided tracheal intubation. 952 patients (96.4%) could be intubated upon the first attempt and overall intubation success was 99.5% (983 out of 988). CONCLUSION: Our study demonstrates that HEMS physicians performed airway management frequently and that both the first attempt as well as the overall success rate of tracheal intubation was high. Together with the fact that all failed and difficult intubations were successfully recognized and handled and that no surgical airway had to be established, the current study once more underlines the importance of proper training of HEMS care providers regarding airway management.


Assuntos
Resgate Aéreo , Anestesiologistas/estatística & dados numéricos , Intubação Intratraqueal/estatística & dados numéricos , Adulto , Idoso , Anestésicos/uso terapêutico , Competência Clínica , Feminino , Humanos , Intubação Intratraqueal/efeitos adversos , Laringoscopia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Recursos Humanos
11.
Medicine (Baltimore) ; 95(18): e3561, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27149475

RESUMO

Cardiopulmonary resuscitation (CPR) is indicated in patients suffering from out-of-hospital cardiac arrest. Several studies suggest a sex- and age-based bias in the treatment of these patients. This particular bias may have a significant impact on the patient's outcome. However, the reasons for these findings are still unclear and discussed controversially. Therefore, the aim of this study was to retrospectively analyze treatment and out-of-hospital survival rates for potential sex- and age-based differences in patients requiring out-of-hospital CPR provided by an emergency physician in the city of Zurich, Switzerland.A total of 3961 consecutive patients (2003-2009) were included in this retrospective analysis to determine the frequency of out-of-hospital CPR and prehospital survival rate, and to identify potential sex- and age-based differences regarding survival and treatment of the patients.Seven hundred fifty-seven patients required CPR during the study period. Seventeen patients had to be excluded because of incomplete or inconclusive documentation, resulting in 743 patients (511 males, 229 females) undergoing further statistical analysis. Female patients were significantly older, compared with male patients (68 ±â€Š18 [mean ±â€ŠSD] vs 64 ±â€Š18 years, P = .012). Men were resuscitated slightly more often than women (86.4% vs 82.1%). Overall out-of-hospital mortality rate was found to be 81.2% (492/632 patients) with no differences between sexes (82.1% for males vs 79% for females, odds ratio 1.039, 95% confidence interval 0.961-1.123). No sex differences were detected in out-of-hospital treatment, as assessed by the different medications administered, initial prehospital Glasgow Coma Scale, and prehospital suspected leading diagnosis.The data of our study demonstrate that there was no sex-based bias in treating patients requiring CPR in the prehospital setting in our physician-led emergency ambulance service.


Assuntos
Parada Cardíaca Extra-Hospitalar/etiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar/estatística & dados numéricos , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
12.
PLoS One ; 11(5): e0155997, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27195693

RESUMO

INTRODUCTION: Sufficient ventilation and oxygenation through proper airway management is essential in patients undergoing cardio-pulmonary resuscitation (CPR). Although widely discussed, securing the airway using an endotracheal tube is considered the standard of care. Endotracheal intubation may be challenging and causes prolonged interruption of chest compressions. Videolaryngoscopes have been introduced to better visualize the vocal cords and accelerate intubation, which makes endotracheal intubation much safer and may contribute to intubation success. Therefore, we aimed to compare hands-off time and intubation success of direct laryngoscopy with videolaryngoscopy (C-MAC, Karl Storz, Tuttlingen, Germany) in a randomized, cross-over manikin study. METHODS: Twenty-six anesthesia residents and twelve anesthesia consultants of the University Hospital Zurich were recruited through a voluntary enrolment. All participants performed endotracheal intubation using direct laryngoscopy and C-MAC in a random order during ongoing chest compressions. Participants were strictly advised to stop chest compression only if necessary. RESULTS: The median hands-off time was 1.9 seconds in direct laryngoscopy, compared to 3 seconds in the C-MAC group. In direct laryngoscopy 39 intubation attempts were recorded, resulting in an overall first intubation attempt success rate of 97%, compared to 38 intubation attempts and 100% overall first intubation attempt success rate in the C-MAC group. CONCLUSION: As a conclusion, the results of our manikin-study demonstrate that video laryngoscopes might not be beneficial compared to conventional, direct laryngoscopy in easily accessible airways under CPR conditions and in experienced hands. The benefits of video laryngoscopes are of course more distinct in overcoming difficult airways, as it converts a potential "blind intubation" into an intubation under visual control.


Assuntos
Reanimação Cardiopulmonar/métodos , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Cirurgia Vídeoassistida/métodos , Adulto , Reanimação Cardiopulmonar/normas , Estudos Cross-Over , Feminino , Humanos , Intubação Intratraqueal/normas , Laringoscopia/normas , Masculino , Manequins , Duração da Cirurgia , Distribuição Aleatória , Cirurgia Vídeoassistida/normas
13.
Resuscitation ; 102: 70-4, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26921473

RESUMO

BACKGROUND: Chest compressions and ventilation are lifesaving tasks during cardio-pulmonary resuscitation (CPR). Besides oxygenation, endotracheal intubation (ETI) during CPR is performed to avoid aspiration of gastric contents. If intubation is difficult or impossible, supraglottic airway devices are utilized. We tested six different airway devices regarding their potential to protect against regurgitation and aspiration during CPR in a randomized experimental human cadaver study. METHODS: Five-hundred ml of 0.01% methylene-blue-solution were instilled into the stomach of 30 adult human cadavers via an oro-gastric tube. The cadavers were then randomly assigned to one of six groups, resulting in 5 cadavers in each group. Airway management was performed with either bag-valve ventilation, Laryngeal Tube, EasyTube, Laryngeal Mask (Classic), I-Gel, or ETI. Thereafter 5min of CPR were performed according to the 2010 Guidelines of the European Resuscitation Council. Pulmonary aspiration was defined as the presence of methylene-blue-solution below the vocal cords or the ETI cuff as assessed by fiber-optic bronchoscopy. RESULTS: Thirty cadavers were included (14 females, 16 males). Aspiration was detected in three out of five cadavers receiving bag-valve ventilation and in two out of five intubated with LMA or I-Gel. In cadavers intubated with the LT, aspiration occurred in one out of five cases. No aspiration could be detected in cadavers intubated with ETI and EasyTube. CONCLUSION: This study provides experimental evidence that, during CPR, ETI offers superior protection against regurgitation and pulmonary aspiration of gastric contents than supraglottic airway devices or bag-valve ventilation.


Assuntos
Manuseio das Vias Aéreas/instrumentação , Reanimação Cardiopulmonar/métodos , Intubação Intratraqueal/instrumentação , Máscaras Laríngeas , Refluxo Laringofaríngeo/prevenção & controle , Pneumonia Aspirativa/prevenção & controle , Respiração Artificial/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Cadáver , Desenho de Equipamento , Feminino , Parada Cardíaca/terapia , Humanos , Masculino , Manequins , Pessoa de Meia-Idade , Projetos Piloto
14.
Crit Care ; 19: 45, 2015 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-25887642

RESUMO

INTRODUCTION: Severe sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. Volatile anesthetics have been shown to attenuate inflammation in a variety of different settings. We therefore hypothesized that volatile anesthetic agents may offer beneficial immunomodulatory effects during the course of long-term intra-abdominal sepsis in rats under continuous sedation and ventilation for up to 24 hours. METHODS: Sham operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats followed by mechanical ventilation. Animals were sedated for 24 hours with propofol (7 to 20 mg/kg/h), sevoflurane, desflurane or isoflurane (0.7 minimal alveolar concentration each). RESULTS: Septic animals sedated with propofol showed a mean survival time of 12 hours, whereas >56% of all animals in the volatile groups survived 24 hours (P <0.001). After 18 hours, base excess in propofol + CLP animals (-20.6 ± 2.0) was lower than in the volatile groups (isoflurane + CLP: -11.7 ± 4.2, sevoflurane + CLP: -11.8 ± 3.5, desflurane + CLP -14.2 ± 3.7; all P <0.03). Plasma endotoxin levels reached 2-fold higher levels in propofol + CLP compared to isoflurane + CLP animals at 12 hours (P <0.001). Also blood levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1ß, interleukin-10, CXCL-2, interferon-γ and high mobility group protein-1) were accentuated in propofol + CLP rats compared to the isoflurane + CLP group at the same time point (P <0.04). CONCLUSIONS: This is the first study to assess prolonged effects of sepsis and long-term application of volatile sedatives compared to propofol on survival, cardiovascular, inflammatory and end organ parameters. Results indicate that volatile anesthetics dramatically improved survival and attenuate systemic inflammation as compared to propofol. The main mechanism responsible for adverse propofol effects could be an enhanced plasma endotoxin concentration, leading to profound hypotension, which was unresponsive to fluid resuscitation.


Assuntos
Anestésicos Intravenosos/efeitos adversos , Propofol/efeitos adversos , Respiração Artificial , Sepse/mortalidade , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Sepse/complicações
15.
Resuscitation ; 90: 42-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25708959

RESUMO

INTRODUCTION: In the prehospital setting, advanced airway management is challenging as it is frequently affected by facial trauma, pharyngeal obstruction or limited access to the patient and/or the patient's airway. Therefore, incidence of prehospital difficult airway management is likely to be higher compared to the in-hospital setting and success rates of advanced airway management range between 80 and 99%. METHODS: 3961 patients treated by an emergency physician in Zurich, Switzerland were included in this retrospective analysis in order to determine the incidence of a difficult airway along with potential circumstantial risk factors like gender, necessity of CPR, NACA score, GCS, use and type of muscle relaxant and use of hypnotic drugs. RESULTS: 692 patients underwent advanced prehospital airway management. Seven patients were excluded due to incomplete or incongruent documentation, resulting in 685 patients included in the statistical analysis. Difficult intubation was recorded in 22 patients, representing an incidence of a difficult airway of 3.2%. Of these 22 patients, 15 patients were intubated successfully, whereas seven patients (1%) had to be ventilated with a bag valve mask during the whole procedure. CONCLUSION: In this physician-led service one out of five prehospital patients requires airway management. Incidence of advanced prehospital difficult airway management is 3.2% and eventual success rate is 99%, if performed by trained emergency physicians. A total of 1% of all prehospital intubation attempts failed and alternative airway device was necessary.


Assuntos
Manuseio das Vias Aéreas , Serviços Médicos de Emergência , Intubação Intratraqueal , Médicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Reanimação Cardiopulmonar , Uso de Medicamentos , Feminino , Escala de Coma de Glasgow , Humanos , Hipnóticos e Sedativos/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Relaxantes Musculares Centrais/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
16.
BMC Anesthesiol ; 14: 61, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25100922

RESUMO

BACKGROUND: Robotic-assisted laparoscopic prostatectomy (RALP) gained much popularity during the last decade. Although the influence of intraoperative fluid management on patients' outcome has been largely discussed in general, its impact on perioperative complications and length of hospitalization in patients undergoing RALP has not been examined so far. We hypothesized that a more restrictive fluid management might lead to a shortened length of hospitalization and a decreased rate of complications in our patients. METHODS: Retrospective analysis of data of 182 patients undergoing RALP at an University Hospital (first series of RALP performed at the center). RESULTS: The amount of fluid administered was initially normalized for body mass index of the patient and the duration of the operation and additionally corrected for age and the interaction of these variables. The application of crystalloids (multiple linear regression model, estimate = -0.044, p = 0.734) had no effect on the length of hospitalization, whereas a negative effect was found for colloids (estimate = -8.317, p = 0.021). Additionally, a significant interaction term between age and the amount of colloid applied (estimate = 0.129, p = 0.028) was calculated. Evaluation of the influence of intraoperative fluid administration using multiple logistic regression models corrected for body mass index, duration of the surgery and additionally for age revealed a negative effect of crystalloids on the incidence of an anastomotic leak between bladder and urethra (estimate = -23.860, p = 0.017), with a significant interaction term between age and the amount of crystalloids (estimate = 0.396, p = 0.0134). Colloids had no significant effect on this particular complication (estimate = 1.887, p = 0.524). Intraoperative blood loss did not alter the incidence of an anastomotic leak (estimate = 0.001, p = 0.086), nor did it affect the length of hospitalization (estimate = 0.0001, p = 0.351). CONCLUSIONS: In accordance to the findings of our study, we suggest that a standardized, more restrictive fluid management might be beneficial in patients undergoing RALP. In older patients this measure would be able to shorten the length of hospitalization and to decrease the incidence of anastomosis leakage as a major complication.


Assuntos
Hidratação/métodos , Laparoscopia/métodos , Prostatectomia/métodos , Robótica/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica/fisiopatologia , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/terapia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
17.
BMC Anesthesiol ; 14: 57, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25097454

RESUMO

BACKGROUND: Acute lung injury (ALI) is associated with high mortality due to the lack of effective therapeutic strategies. Mechanical ventilation itself can cause ventilator-induced lung injury. Pulmonary vascular barrier function, regulated in part by Src kinase-dependent phosphorylation of caveolin-1 and intercellular adhesion molecule-1 (ICAM-1), plays a crucial role in the development of protein-/neutrophil-rich pulmonary edema, the hallmark of ALI. Amide-linked local anesthetics, such as ropivacaine, have anti-inflammatory properties in experimental ALI. We hypothesized ropivacaine may attenuate inflammation in a "double-hit" model of ALI triggered by bacterial endotoxin plus hyperinflation via inhibition of Src-dependent signaling. METHODS: C57BL/6 (WT) and ICAM-1 (-/-) mice were exposed to either nebulized normal saline (NS) or lipopolysaccharide (LPS, 10 mg) for 1 hour. An intravenous bolus of 0.33 mg/kg ropivacaine or vehicle was followed by mechanical ventilation with normal (7 ml/kg, NTV) or high tidal volume (28 ml/kg, HTV) for 2 hours. Measures of ALI (excess lung water (ELW), extravascular plasma equivalents, permeability index, myeloperoxidase activity) were assessed and lungs were homogenized for Western blot analysis of phosphorylated and total Src, ICAM-1 and caveolin-1. Additional experiments evaluated effects of ropivacaine on LPS-induced phosphorylation/expression of Src, ICAM-1 and caveolin-1 in human lung microvascular endothelial cells (HLMVEC). RESULTS: WT mice treated with LPS alone showed a 49% increase in ELW compared to control animals (p = 0.001), which was attenuated by ropivacaine (p = 0.001). HTV ventilation alone increased measures of ALI even more than LPS, an effect which was not altered by ropivacaine. LPS plus hyperinflation ("double-hit") increased all ALI parameters (ELW, EVPE, permeability index, MPO activity) by 3-4 fold compared to control, which were again decreased by ropivacaine. Western blot analyses of lung homogenates as well as HLMVEC treated in culture with LPS alone showed a reduction in Src activation/expression, as well as ICAM-1 expression and caveolin-1 phosphorylation. In ICAM-1 (-/-) mice, neither addition of LPS to HTV ventilation alone nor ropivacaine had an effect on the development of ALI. CONCLUSIONS: Ropivacaine may be a promising therapeutic agent for treating the cause of pulmonary edema by blocking inflammatory Src signaling, ICAM-1 expression, leukocyte infiltration, and vascular hyperpermeability.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Amidas/farmacologia , Anestésicos Locais/farmacologia , Quinases da Família src/antagonistas & inibidores , Lesão Pulmonar Aguda/etiologia , Animais , Caveolina 1/genética , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Molécula 1 de Adesão Intercelular/genética , Lipopolissacarídeos/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação/efeitos dos fármacos , Edema Pulmonar/prevenção & controle , Ropivacaina , Transdução de Sinais/efeitos dos fármacos , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Quinases da Família src/metabolismo
18.
Anesthesiology ; 120(6): 1414-28, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24525631

RESUMO

BACKGROUND: Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase-Akt-nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability. METHODS: Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed. RESULTS: Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10 M for ropivacaine; IC50 = 5.864 × 10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10 M for ropivacaine; IC50 = 6.377 × 10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated. CONCLUSIONS: Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial cells by attenuating p85 recruitment to TNF-receptor-1. The resultant decrease in Akt, endothelial nitric oxide synthase, and Src phosphorylation reduced neutrophil adhesion and endothelial hyperpermeability. This novel anti-inflammatory "side-effect" of ropivacaine and lidocaine may provide therapeutic benefit in acute inflammatory disease.


Assuntos
Amidas/farmacologia , Anestésicos Locais/farmacologia , Endotélio Vascular/efeitos dos fármacos , Lidocaína/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Quinases da Família src/metabolismo , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/enzimologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Humanos , Pulmão/efeitos dos fármacos , Pulmão/enzimologia , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Ropivacaina , Fator de Necrose Tumoral alfa/administração & dosagem , Quinases da Família src/fisiologia
19.
Life Sci ; 98(2): 88-95, 2014 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-24447628

RESUMO

AIMS: Dobutamine is cytoprotective when applied before a subsequent stress. However, the underlying molecular mechanism is unknown. Dobutamine also inhibits nuclear factor (NF)-κB in human T lymphocytes. Other inhibitors of NF-κB induce a so-called heat shock response. We hypothesized that dobutamine mediates protection from apoptotic cell death by the induction of a heat shock response. MAIN METHODS: Jurkat T lymphoma cells were preincubated with dobutamine (0.1, 0.5 mM) before the induction of apoptosis (staurosporine, 2 µM). DNA-binding of heat shock factor (HSF)-1 was analyzed by electrophoretic mobility shift assay, mRNA-expression of heat shock protein (hsp)70 and hsp90 by Northern Blot, activity of caspase-3 by fluorogenic caspase activity assay and cleavage of pro-caspase-3 by Western Blot. Apoptosis was assessed by flow cytometry after annexin V-fluorescein isothiocyanate staining. Hsp70 and hsp90 were inhibited using N-formyl-3,4-methylenedioxy-benzylidene-gamma-butyrolaetam and 17-allylamino-17-demethoxygeldana-mycin, respectively. All data are given as median and 25/75% percentile. KEY FINDINGS: Pre-incubation with dobutamine inhibited staurosporine-induced annexin V-fluorescence (28 [20-32] % vs. 12 [9-15] % for dobutamine 0.1 mM and 7 [5-12] % for dobutamine 0.5 mM, p<0.001), cleavage of pro-caspase-3 as well as caspase-3-like activity (0.46 [0.40-0.48] vs. 0.32 [0.27-0.39] for Dobutamine 0.1 mM and 0.20 [0.19-0.23] for Dobutamine 0.5 mM, p<0.01). Dobutamine induced DNA-binding of HSF-1 and mRNA-expression of hsp70 and hsp90. While inhibition of Hsp90 had no effect, inhibition of Hsp70 increased the number of annexin V-positive cells (33 [32-36] % vs. 18 [16-24] %) and caspase-3-like activity (0.21 [0.19-0.23] vs. 0.16 [0.13-0.17], p<0.05). SIGNIFICANCE: Dobutamine protects from apoptotic cell death via the induction of Hsp70.


Assuntos
Citoproteção/efeitos dos fármacos , Dobutamina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/genética , Agonistas de Receptores Adrenérgicos beta 1/farmacologia , Apoptose/efeitos dos fármacos , Northern Blotting , Linhagem Celular Tumoral , Eletroforese em Gel de Poliacrilamida , Citometria de Fluxo , Proteínas de Choque Térmico HSP70/metabolismo , Humanos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
20.
Pulm Circ ; 3(4): 816-30, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25006397

RESUMO

In the present study, we tested the hypothesis that chronic inflammation and oxidative/nitrosative stress induce caveolin 1 (Cav-1) degradation, providing an underlying mechanism of endothelial cell activation/dysfunction and pulmonary vascular remodeling in patients with idiopathic pulmonary arterial hypertension (IPAH). We observed reduced Cav-1 protein despite increased Cav-1 messenger RNA expression and also endothelial nitric oxide synthase (eNOS) hyperphosphorylation in human pulmonary artery endothelial cells (PAECs) from patients with IPAH. In control human lung endothelial cell cultures, tumor necrosis factor α-induced nitric oxide (NO) production and S-nitrosation (SNO) of Cav-1 Cys-156 were associated with Src displacement and activation, Cav-1 Tyr-14 phosphorylation, and destabilization of Cav-1 oligomers within 5 minutes that could be blocked by eNOS or Src inhibition. Prolonged stimulation (72 hours) with NO donor DETANONOate reduced oligomerized and total Cav-1 levels by 40%-80%, similar to that observed in IPAH patient-derived PAECs. NO donor stimulation of endothelial cells for >72 hours, which was associated with sustained Src activation and Cav-1 phosphorylation, ubiquitination, and degradation, was blocked by NOS inhibitor L-NAME, Src inhibitor PP2, and proteosomal inhibitor MG132. Thus, chronic inflammation, sustained eNOS and Src signaling, and Cav-1 degradation may be important causal factors in the development of IPAH by promoting PAEC dysfunction/activation via sustained oxidative/nitrosative stress.

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