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1.
J Clin Anesth ; 99: 111565, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39316931

RESUMEN

STUDY OBJECTIVE: Male sex has inconsistently been associated with the development of postoperative pulmonary complications (PPCs). These studies were different in size, design, population and preoperative risk. We reanalysed the database of 'Local ASsessment of Ventilatory management during General Anaesthesia for Surgery study' (LAS VEGAS) to evaluate differences between females and males with respect to PPCs. DESIGN, SETTING AND PATIENTS: Post hoc unmatched and matched analysis of LAS VEGAS, an international observational study in patients undergoing intraoperative ventilation under general anaesthesia for surgery in 146 hospitals across 29 countries. The primary endpoint was a composite of PPCs in the first 5 postoperative days. Individual PPCs, hospital length of stay and mortality were secondary endpoints. Propensity score matching was used to create a similar cohort regarding type of surgery and epidemiological factors with a known association with development of PPCs. MAIN RESULTS: The unmatched cohort consisted of 9697 patients; 5342 (55.1%) females and 4355 (44.9%) males. The matched cohort consisted of 6154 patients; 3077 (50.0%) females and 3077 (50.0%) males. The incidence in PPCs was neither significant between females and males in the unmatched cohort (10.0 vs 10.7%; odds ratio (OR) 0.93 [0.81-1.06]; P = 0.255), nor in the matched cohort (10.5 vs 10.0%; OR 1.05 [0.89-1.25]; P = 0.556). New invasive ventilation occurred less often in females in the unmatched cohort. Hospital length of stay and mortality were similar between females and males in both cohorts. CONCLUSIONS: In this conveniently-sized worldwide cohort of patients receiving intraoperative ventilation under general anaesthesia for surgery, the PPC incidence was not significantly different between sexes. REGISTRATION: LAS VEGAS was registered at clinicaltrial.gov (study identifier NCT01601223).

2.
Crit Care ; 28(1): 269, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39217380

RESUMEN

This review explores the complex interactions between sedation and invasive ventilation and examines the potential of volatile anesthetics for lung- and diaphragm-protective sedation. In the early stages of invasive ventilation, many critically ill patients experience insufficient respiratory drive and effort, leading to compromised diaphragm function. Compared with common intravenous agents, inhaled sedation with volatile anesthetics better preserves respiratory drive, potentially helping to maintain diaphragm function during prolonged periods of invasive ventilation. In turn, higher concentrations of volatile anesthetics reduce the size of spontaneously generated tidal volumes, potentially reducing lung stress and strain and with that the risk of self-inflicted lung injury. Taken together, inhaled sedation may allow titration of respiratory drive to maintain inspiratory efforts within lung- and diaphragm-protective ranges. Particularly in patients who are expected to require prolonged invasive ventilation, in whom the restoration of adequate but safe inspiratory effort is crucial for successful weaning, inhaled sedation represents an attractive option for lung- and diaphragm-protective sedation. A technical limitation is ventilatory dead space introduced by volatile anesthetic reflectors, although this impact is minimal and comparable to ventilation with heat and moisture exchangers. Further studies are imperative for a comprehensive understanding of the specific effects of inhaled sedation on respiratory drive and effort and, ultimately, how this translates into patient-centered outcomes in critically ill patients.


Asunto(s)
Anestésicos por Inhalación , Diafragma , Respiración Artificial , Humanos , Diafragma/efectos de los fármacos , Anestésicos por Inhalación/administración & dosificación , Anestésicos por Inhalación/farmacología , Respiración Artificial/métodos , Pulmón/efectos de los fármacos , Pulmón/fisiología
3.
Anesthesiology ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39042027

RESUMEN

BACKGROUND: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. Our objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. METHODS: Multilevel Bayesian logistic regression analysis on individual patient data from three randomized clinical trials carried out on surgical patients at Intermediate-to-High Risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. We studied the effect of high PEEP with recruitment maneuvers versus Low PEEP Ventilation. Priors were chosen to reflect neutral, pessimistic, and optimistic expectations of the treatment effect. RESULTS: Using a neutral, pessimistic, or optimistic prior, the posterior mean odds ratio (OR) for High PEEP with recruitment maneuvers compared to Low PEEP was 0.85 (95% Credible Interval [CrI] 0.71 to 1.02), 0.87 (0.72 to 1.04), and 0.86 (0.71 to 1.02), respectively. Regardless of prior beliefs, the posterior probability of experiencing a beneficial effect exceeded 90%. Subgroup analysis indicated a more pronounced effect in patients who underwent laparoscopy (OR: 0.67 [0.50 to 0.87]) and those at high risk for PPCs (OR: 0.80 [0.53 to 1.13]). Sensitivity analysis, considering severe postoperative pulmonary complications only or applying a different heterogeneity prior, yielded consistent results. CONCLUSION: High PEEP with recruitment maneuvers demonstrated a moderate reduction in the probability of PPC occurrence, with a high posterior probability of benefit observed consistently across various prior beliefs, particularly among patients who underwent laparoscopy.

4.
Trials ; 25(1): 313, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730383

RESUMEN

BACKGROUND: Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing. METHODS: The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time. DISCUSSION: Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries. TRIAL REGISTRATION: ClinicalTrials.gov NCT05085288 Registered October 20, 2021.


Asunto(s)
Terapia por Estimulación Eléctrica , Estudios Multicéntricos como Asunto , Úlcera por Presión , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Úlcera por Presión/terapia , Terapia por Estimulación Eléctrica/métodos , Resultado del Tratamiento , Factores de Tiempo , Cicatrización de Heridas
5.
J Clin Anesth ; 96: 111485, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38718685

RESUMEN

STUDY OBJECTIVE: To estimate the incidence of postoperative oxygenation impairment after lung resection in the era of lung-protective management, and to identify perioperative factors associated with that impairment. DESIGN: Registry-based retrospective cohort study. SETTING: Two large academic hospitals in the United States. PATIENTS: 3081 ASA I-IV patients undergoing lung resection. MEASUREMENTS: 79 pre- and intraoperative variables, selected for inclusion based on a causal inference framework. The primary outcome of impaired oxygenation, an early marker of lung injury, was defined as at least one of the following within seven postoperative days: (1) SpO2 < 92%; (2) imputed PaO2/FiO2 < 300 mmHg [(1) or (2) occurring at least twice within 24 h]; (3) intensive oxygen therapy (mechanical ventilation or > 50% oxygen or high-flow oxygen). MAIN RESULTS: Oxygenation was impaired within seven postoperative days in 70.8% of patients (26.6% with PaO2/FiO2 < 200 mmHg or intensive oxygen therapy). In multivariable analysis, each additional cmH2O of intraoperative median driving pressure was associated with a 7% higher risk of impaired oxygenation (OR 1.07; 95%CI 1.04 to 1.10). Higher median intraoperative FiO2 (OR 1.23; 95%CI 1.14 to 1.31 per 0.1) and PEEP (OR 1.12; 95%CI 1.04 to 1.21 per 1 cm H2O) were also associated with increased risk. History of COPD (OR 2.55; 95%CI 1.95 to 3.35) and intraoperative albuterol administration (OR 2.07; 95%CI 1.17 to 3.67) also showed reliable effects. CONCLUSIONS: Impaired postoperative oxygenation is common after lung resection and is associated with potentially modifiable pre- and intraoperative respiratory factors.


Asunto(s)
Terapia por Inhalación de Oxígeno , Neumonectomía , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Incidencia , Factores de Riesgo , Neumonectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Terapia por Inhalación de Oxígeno/estadística & datos numéricos , Terapia por Inhalación de Oxígeno/métodos , Sistema de Registros/estadística & datos numéricos , Oxígeno/sangre , Respiración con Presión Positiva/efectos adversos , Respiración con Presión Positiva/métodos , Estados Unidos/epidemiología
6.
BMC Anesthesiol ; 24(1): 166, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702641

RESUMEN

BACKGROUND: Pregnancy is associated with an increased risk of pulmonary aspiration during general anaesthesia, but the incidence of this complication is not well defined. METHODS: We performed a retrospective database review in a tertiary care university hospital to determine the incidence of pulmonary aspiration in pregnant patients undergoing endotracheal intubation, with and without Rapid Sequence Induction (RSI), as well as face-mask ventilation and supraglottic airway devices. We included Patients in the 2nd or 3rd trimester of pregnancy and immediate postpartum undergoing surgical procedures. The primary endpoint was the occurrence of pulmonary aspiration. RESULTS: Data from 2,390 patients undergoing general anaesthesia for cerclage of cervix uteri, manual removal of retained placenta, repair of obstetric laceration, or postpartum bleeding were retrospectively evaluated. A supraglottic airway device or face-mask ventilation was used in 1,425/2,390 (60%) of patients, while 638/2,390 (27%) were intubated. RSI was used in 522/638 (82%) of patients undergoing tracheal intubation, or 522/2,390 (22%) of the entire cohort. In-depth review of the charts, including 54 patients who had been initially classified as "possible pulmonary aspiration" by anaesthetists, revealed that this adverse event did not occur in the cohort. CONCLUSIONS: In conclusion, in this obstetric surgery patient population at risk for pulmonary aspiration, supraglottic airway devices were used in approximately 60% of cases. Yet, no aspiration event was detected with either a supraglottic airway or endotracheal intubation.


Asunto(s)
Manejo de la Vía Aérea , Hospitales Universitarios , Intubación Intratraqueal , Aspiración Respiratoria , Humanos , Femenino , Estudios Retrospectivos , Embarazo , Adulto , Manejo de la Vía Aérea/métodos , Intubación Intratraqueal/métodos , Aspiración Respiratoria/prevención & control , Aspiración Respiratoria/etiología , Periodo Posparto , Centros de Atención Terciaria , Anestesia General/métodos
7.
Anesthesiology ; 141(1): 44-55, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38625679

RESUMEN

BACKGROUND: During one-lung ventilation (OLV), positive end-expiratory pressure (PEEP) can improve lung aeration but might overdistend lung units and increase intrapulmonary shunt. The authors hypothesized that higher PEEP shifts pulmonary perfusion from the ventilated to the nonventilated lung, resulting in a U-shaped relationship with intrapulmonary shunt during OLV. METHODS: In nine anesthetized female pigs, a thoracotomy was performed and intravenous lipopolysaccharide infused to mimic the inflammatory response of thoracic surgery. Animals underwent OLV in supine position with PEEP of 0 cm H2O, 5 cm H2O, titrated to best respiratory system compliance, and 15 cm H2O (PEEP0, PEEP5, PEEPtitr, and PEEP15, respectively, 45 min each, Latin square sequence). Respiratory, hemodynamic, and gas exchange variables were measured. The distributions of perfusion and ventilation were determined by IV fluorescent microspheres and computed tomography, respectively. RESULTS: Compared to two-lung ventilation, the driving pressure increased with OLV, irrespective of the PEEP level. During OLV, cardiac output was lower at PEEP15 (5.5 ± 1.5 l/min) than PEEP0 (7.6 ± 3 l/min) and PEEP5 (7.4 ± 2.9 l/min; P = 0.004), while the intrapulmonary shunt was highest at PEEP0 (PEEP0: 48.1% ± 14.4%; PEEP5: 42.4% ± 14.8%; PEEPtitr: 37.8% ± 11.0%; PEEP15: 39.0% ± 10.7%; P = 0.027). The relative perfusion of the ventilated lung did not differ among PEEP levels (PEEP0: 65.0% ± 10.6%; PEEP5: 68.7% ± 8.7%; PEEPtitr: 68.2% ± 10.5%; PEEP15: 58.4% ± 12.8%; P = 0.096), but the centers of relative perfusion and ventilation in the ventilated lung shifted from ventral to dorsal and from cranial to caudal zones with increasing PEEP. CONCLUSIONS: In this experimental model of thoracic surgery, higher PEEP during OLV did not shift the perfusion from the ventilated to the nonventilated lung, thus not increasing intrapulmonary shunt.


Asunto(s)
Estudios Cruzados , Ventilación Unipulmonar , Respiración con Presión Positiva , Animales , Respiración con Presión Positiva/métodos , Porcinos , Femenino , Ventilación Unipulmonar/métodos , Intercambio Gaseoso Pulmonar/fisiología , Pulmón/fisiología , Circulación Pulmonar/fisiología , Distribución Aleatoria , Hemodinámica/fisiología
8.
J Clin Anesth ; 95: 111444, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38583224

RESUMEN

BACKGROUND: Mechanical ventilation with variable tidal volumes (V-VCV) has the potential to improve lung function during general anesthesia. We tested the hypothesis that V-VCV compared to conventional volume-controlled ventilation (C-VCV) would improve intraoperative arterial oxygenation and respiratory system mechanics in patients undergoing thoracic surgery under one-lung ventilation (OLV). METHODS: Patients were randomized to V-VCV (n = 39) or C-VCV (n = 39). During OLV tidal volume of 5 mL/kg predicted body weight (PBW) was used. Both groups were ventilated with a positive end-expiratory pressure (PEEP) of 5 cm H2O, inspiration to expiration ratio (I:E) of 1:1 (during OLV) and 1:2 during two-lung ventilation, the respiratory rate (RR) titrated to arterial pH, inspiratory peak-pressure ≤ 40 cm H2O and an inspiratory oxygen fraction of 1.0. RESULTS: Seventy-five out of 78 Patients completed the trial and were analyzed (dropouts were excluded). The partial pressure of arterial oxygen (PaO2) 20 min after the start of OLV did not differ among groups (V-VCV: 25.8 ± 14.6 kPa vs C-VCV: 27.2 ± 15.3 kPa; mean difference [95% CI]: 1.3 [-8.2, 5.5], P = 0.700). Furthermore, intraoperative gas exchange, intraoperative adverse events, need for rescue maneuvers due to desaturation and hypercapnia, incidence of postoperative pulmonary and extra-pulmonary complications, and hospital free days at day 30 after surgery did not differ between groups. CONCLUSIONS: In thoracic surgery patients under OLV, V-VCV did not improve oxygenation or respiratory system mechanics compared to C-VCV. Ethical Committee: EK 420092019. TRIAL REGISTRATION: at the German Clinical Trials Register: DRKS00022202 (16.06.2020).


Asunto(s)
Ventilación Unipulmonar , Intercambio Gaseoso Pulmonar , Mecánica Respiratoria , Procedimientos Quirúrgicos Torácicos , Volumen de Ventilación Pulmonar , Humanos , Ventilación Unipulmonar/métodos , Ventilación Unipulmonar/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Procedimientos Quirúrgicos Torácicos/efectos adversos , Procedimientos Quirúrgicos Torácicos/métodos , Anciano , Respiración con Presión Positiva/métodos , Respiración con Presión Positiva/efectos adversos , Anestesia General/métodos , Respiración Artificial/métodos , Oxígeno/sangre , Oxígeno/administración & dosificación
10.
J Crit Care ; 81: 154531, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38341938

RESUMEN

PURPOSE: We investigated driving pressure (ΔP) and mechanical power (MP) and associations with clinical outcomes in critically ill patients ventilated for reasons other than ARDS. MATERIALS AND METHODS: Individual patient data analysis of a pooled database that included patients from four observational studies of ventilation. ΔP and MP were compared among invasively ventilated non-ARDS patients with sepsis, with pneumonia, and not having sepsis or pneumonia. The primary endpoint was ΔP; secondary endpoints included MP, ICU mortality and length of stay, and duration of ventilation. RESULTS: This analysis included 372 (11%) sepsis patients, 944 (28%) pneumonia patients, and 2040 (61%) patients ventilated for any other reason. On day 1, median ΔP was higher in sepsis (14 [11-18] cmH2O) and pneumonia patients (14 [11-18]cmH2O), as compared to patients not having sepsis or pneumonia (13 [10-16] cmH2O) (P < 0.001). Median MP was also higher in sepsis and pneumonia patients. ΔP, as opposed to MP, was associated with ICU mortality in sepsis and pneumonia patients. CONCLUSIONS: The intensity of ventilation differed between patients with sepsis or pneumonia and patients receiving ventilation for any other reason; ΔP was associated with higher mortality in sepsis and pneumonia patients. REGISTRATION: This post hoc analysis was not registered; the individual studies that were merged into the used database were registered at clinicaltrials.gov: NCT01268410 (ERICC), NCT02010073 (LUNG SAFE), NCT01868321 (PRoVENT), and NCT03188770 (PRoVENT-iMiC).


Asunto(s)
Neumonía , Síndrome de Dificultad Respiratoria , Sepsis , Humanos , Respiración Artificial/efectos adversos , Unidades de Cuidados Intensivos , Pulmón , Síndrome de Dificultad Respiratoria/terapia , Síndrome de Dificultad Respiratoria/etiología , Sepsis/terapia , Sepsis/etiología
11.
Anesth Analg ; 138(4): 821-828, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36920865

RESUMEN

BACKGROUND: Obesity distorts airways and slightly complicates intubations in adults, but whether obesity complicates pediatric intubations remains unclear. We, therefore, tested the primary hypothesis that increasing age- and sex-specific body mass index (BMI) percentile is associated with difficult intubation, defined as >1 intubation attempt. METHODS: We conducted a retrospective analysis of pediatric patients between 2 and 18 years of age who had noncardiac surgery with oral endotracheal intubation. We assessed the association between BMI percentile and difficult intubation, defined as >1 intubation attempt, using a confounder-adjusted multivariable logistic regression model. Secondarily, we assessed whether the main association depended on preoperative substantial airway abnormality status or age group. RESULTS: A total of 9339 patients were included in the analysis. Median [quartiles] age- and sex-specific BMI percentile was 70 [33, 93], and 492 (5.3%) patients had difficult intubation. There was no apparent association between age- and sex-specific BMI percentile and difficult intubation. The estimated odds ratio (OR) for having difficult intubation for a 10-unit increase in BMI percentile was 0.98 (95% confidence interval [CI], 0.95-1.005) and was consistent across the 3 age groups of early childhood, middle childhood, and early adolescence (interaction P = .53). Patients with preoperative substantial airway abnormalities had lower odds of difficult intubation per 10-unit increase in BMI percentile, with OR (95% CI) of 0.83 (0.70-0.98), P = .01. CONCLUSIONS: Age- and sex-specific BMI percentile was not associated with difficult intubation in children between 2 and 18 years of age. As in adults, obesity in children does not much complicate intubation.


Asunto(s)
Obesidad Infantil , Masculino , Adulto , Femenino , Adolescente , Humanos , Niño , Preescolar , Índice de Masa Corporal , Estudios Retrospectivos , Estudios de Cohortes , Intubación Intratraqueal/efectos adversos
12.
J Clin Anesth ; 92: 111242, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37833194

RESUMEN

STUDY OBJECTIVE: We aimed to characterize intra-operative mechanical ventilation with low or high positive end-expiratory pressure (PEEP) and recruitment manoeuvres (RM) regarding intra-tidal recruitment/derecruitment and overdistension using non-linear respiratory mechanics, and mechanical power in obese surgical patients enrolled in the PROBESE trial. DESIGN: Prospective, two-centre substudy of the international, multicentre, two-arm, randomized-controlled PROBESE trial. SETTING: Operating rooms of two European University Hospitals. PATIENTS: Forty-eight adult obese patients undergoing abdominal surgery. INTERVENTIONS: Intra-operative protective ventilation with either PEEP of 12 cmH2O and repeated RM (HighPEEP+RM) or 4 cmH2O without RM (LowPEEP). MEASUREMENTS: The index of intra-tidal recruitment/de-recruitment and overdistension (%E2) as well as airway pressure, tidal volume (VT), respiratory rate (RR), resistance, elastance, and mechanical power (MP) were calculated from respiratory signals recorded after anesthesia induction, 1 h thereafter, and end of surgery (EOS). MAIN RESULTS: Twenty-four patients were analyzed in each group. PEEP was higher (mean ± SD, 11.7 ± 0.4 vs. 3.7 ± 0.6 cmH2O, P < 0.001) and driving pressure lower (12.8 ± 3.5 vs. 21.7 ± 6.8 cmH2O, P < 0.001) during HighPEEP+RM than LowPEEP, while VT and RR did not differ significantly (7.3 ± 0.6 vs. 7.4 ± 0.8 ml∙kg-1, P = 0.835; and 14.6 ± 2.5 vs. 15.7 ± 2.0 min-1, P = 0.150, respectively). %E2 was higher in HighPEEP+RM than in LowPEEP following induction (-3.1 ± 7.2 vs. -12.4 ± 10.2%; P < 0.001) and subsequent timepoints. Total resistance and elastance (13.3 ± 3.8 vs. 17.7 ± 6.8 cmH2O∙l∙s-2, P = 0.009; and 15.7 ± 5.5 vs. 28.5 ± 8.4 cmH2O∙l, P < 0.001, respectively) were lower during HighPEEP+RM than LowPEEP. Additionally, MP was lower in HighPEEP+RM than LowPEEP group (5.0 ± 2.2 vs. 10.4 ± 4.7 J∙min-1, P < 0.001). CONCLUSIONS: In this sub-cohort of PROBESE, intra-operative ventilation with high PEEP and RM reduced intra-tidal recruitment/de-recruitment as well as driving pressure, elastance, resistance, and mechanical power, as compared with low PEEP. TRIAL REGISTRATION: The PROBESE study was registered at www. CLINICALTRIALS: gov, identifier: NCT02148692 (submission for registration on May 23, 2014).


Asunto(s)
Respiración con Presión Positiva , Respiración Artificial , Adulto , Humanos , Estudios Prospectivos , Volumen de Ventilación Pulmonar , Obesidad/complicaciones , Obesidad/cirugía , Mecánica Respiratoria
13.
Front Physiol ; 14: 1253810, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37877098

RESUMEN

Background: Mechanical ventilation (MV) is a life supporting therapy but may also cause lung damage. This phenomenon is known as ventilator-induced lung injury (VILI). A potential pathomechanisms of ventilator-induced lung injury may be the stretch-induced production and release of cytokines and pro-inflammatory molecules from the alveolar epithelium. Yes-associated protein (YAP) might be regulated by mechanical forces and involved in the inflammation cascade. However, its role in stretch-induced damage of alveolar cells remains poorly understood. In this study, we explored the role of YAP in the response of alveolar epithelial type II cells (AEC II) to elevated cyclic stretch in vitro. We hypothesize that Yes-associated protein activates its downstream targets and regulates the interleukin-6 (IL-6) expression in response to 30% cyclic stretch in AEC II. Methods: The rat lung L2 cell line was exposed to 30% cyclic equibiaxial stretch for 1 or 4 h. Non-stretched conditions served as controls. The cytoskeleton remodeling and cell junction integrity were evaluated by F-actin and Pan-cadherin immunofluorescence, respectively. The gene expression and protein levels of IL-6, Yes-associated protein, Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1), and connective tissue growth factor (CTGF/CCN2) were studied by real-time polymerase chain reaction (RT-qPCR) and Western blot, respectively. Verteporfin (VP) was used to inhibit Yes-associated protein activation. The effects of 30% cyclic stretch were assessed by two-way ANOVA. Statistical significance as accepted at p < 0.05. Results: Cyclic stretch of 30% induced YAP nuclear accumulation, activated the transcription of Yes-associated protein downstream targets Cyr61/CCN1 and CTGF/CCN2 and elevated IL-6 expression in AEC II after 1 hour, compared to static control. VP (2 µM) inhibited Yes-associated protein activation in response to 30% cyclic stretch and reduced IL-6 protein levels. Conclusion: In rat lung L2 AEC II, 30% cyclic stretch activated YAP, and its downstream targets Cyr61/CCN1 and CTGF/CCN2 and proinflammatory IL-6 expression. Target activation was blocked by a Yes-associated protein inhibitor. This novel YAP-dependent pathway could be involved in stretch-induced damage of alveolar cells.

14.
Front Physiol ; 14: 1204531, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37601645

RESUMEN

Background. Global and regional transpulmonary pressure (PL) during one-lung ventilation (OLV) is poorly characterized. We hypothesized that global and regional PL and driving PL (ΔPL) increase during protective low tidal volume OLV compared to two-lung ventilation (TLV), and vary with body position. Methods. In sixteen anesthetized juvenile pigs, intra-pleural pressure sensors were placed in ventral, dorsal, and caudal zones of the left hemithorax by video-assisted thoracoscopy. A right thoracotomy was performed and lipopolysaccharide administered intravenously to mimic the inflammatory response due to thoracic surgery. Animals were ventilated in a volume-controlled mode with a tidal volume (VT) of 6 mL kg-1 during TLV and of 5 mL kg-1 during OLV and a positive end-expiratory pressure (PEEP) of 5 cmH2O. Global and local transpulmonary pressures were calculated. Lung instability was defined as end-expiratory PL<2.9 cmH2O according to previous investigations. Variables were acquired during TLV (TLVsupine), left lung ventilation in supine (OLVsupine), semilateral (OLVsemilateral), lateral (OLVlateral) and prone (OLVprone) positions randomized according to Latin-square sequence. Effects of position were tested using repeated measures ANOVA. Results. End-expiratory PL and ΔPL were higher during OLVsupine than TLVsupine. During OLV, regional end-inspiratory PL and ΔPL did not differ significantly among body positions. Yet, end-expiratory PL was lower in semilateral (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and lateral (ventral: 1.9 ± 3.3 cmH2O; caudal: 2.7 ± 1.7 cmH2O) compared to supine (ventral: 4.8 ± 2.9 cmH2O; caudal: 3.1 ± 2.6 cmH2O) and prone position (ventral: 1.7 ± 2.5 cmH2O; caudal: 3.3 ± 1.6 cmH2O), mainly in ventral (p ≤ 0.001) and caudal (p = 0.007) regions. Lung instability was detected more often in semilateral (26 out of 48 measurements; p = 0.012) and lateral (29 out of 48 measurements, p < 0.001) as compared to supine position (15 out of 48 measurements), and more often in lateral as compared to prone position (19 out of 48 measurements, p = 0.027). Conclusion. Compared to TLV, OLV increased lung stress. Body position did not affect stress of the ventilated lung during OLV, but lung stability was lowest in semilateral and lateral decubitus position.

15.
Artículo en Inglés | MEDLINE | ID: mdl-37399834

RESUMEN

BACKGROUND: Not much is known about the results of nonelective anatomical lung resections in coronavirus disease 2019 (COVID-19) patients put on extracorporeal membrane oxygenation (ECMO). The aim of this study was to analyze the outcome of lobectomy under ECMO support in patients with acute respiratory failure due to severe COVID-19. METHODS: All COVID-19 patients undergoing anatomical lung resection with ECMO support at a German university hospital were included into a prospective database. Study period was April 1, 2020, to April 30, 2021 (first, second, and third waves in Germany). RESULTS: A total of nine patients (median age 61 years, interquartile range 10 years) were included. There was virtually no preexisting comorbidity (median Charlson score of comorbidity 0.2). The mean interval between first positive COVID-19 test and surgery was 21.9 days. Clinical symptoms at the time of surgery were sepsis (nine of nine), respiratory failure (nine of nine), acute renal failure (five of nine), pleural empyema (five of nine), lung artery embolism (four of nine), and pneumothorax (two of nine). Mean intensive care unit (ICU) and ECMO days before surgery were 15.4 and 6, respectively. Indications for surgery were bacterial superinfection with lung abscess formation and progressive septic shock (seven of nine) and abscess formation with massive pulmonary hemorrhage into the abscess cavity (two of nine). All patients were under venovenous ECMO with femoral-jugular configuration. Operative procedures were lobectomy (eight) and pneumonectomy (one). Weaning from ECMO was successful in four of nine. In-hospital mortality was five of nine. Mean total ECMO days were 10.3 ± 6.2 and mean total ICU days were 27.7 ± 9.9. Mean length of stay was 28.7 ± 8.8 days. CONCLUSION: Emergency surgery under ECMO support seems to open up a perspective for surgical source control in COVID-19 patients with bacterial superinfection and localized pulmonary abscess.

17.
PLoS One ; 18(4): e0283748, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37023031

RESUMEN

BACKGROUND: Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality after open abdominal surgery. Optimized perioperative lung expansion may minimize the synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction. This ongoing study will assess whether an anesthesia-centered bundle focused on perioperative lung expansion results in decreased incidence and severity of PPCs after open abdominal surgery. METHODS: Prospective multicenter randomized controlled pragmatic trial in 750 adult patients with at least moderate risk for PPCs undergoing prolonged (≥2 hour) open abdominal surgery. Participants are randomized to receive either a bundle intervention focused on perioperative lung expansion or usual care. The bundle intervention includes preoperative patient education, intraoperative protective ventilation with individualized positive end-expiratory pressure to maximize respiratory system compliance, optimized neuromuscular blockade and reversal management, and postoperative incentive spirometry and early mobilization. Primary outcome is the distribution of the highest PPC severity by postoperative day 7. Secondary outcomes include the proportion of participants with: PPC grades 1-2 through POD 7; PPC grades 3-4 through POD 7, 30 and 90; intraoperative hypoxemia, rescue recruitment maneuvers, or cardiovascular events; and any major extrapulmonary postoperative complications. Additional secondary and exploratory outcomes include individual PPCs by POD 7, length of postoperative oxygen therapy or other respiratory support, hospital resource use parameters, Patient-Reported Outcomes Measurements (PROMIS®) questionnaires for dyspnea and fatigue collected before and at days 7, 30 and 90 after surgery, and plasma concentrations of lung injury biomarkers (IL6, IL-8, RAGE, CC16, Ang-2) analyzed from samples obtained before, end of, and 24 hours after surgery. DISCUSSION: Participant recruitment for this study started January 2020; results are expected in 2024. At the conclusion of this trial, we will determine if this anesthesia-centered strategy focused on perioperative lung expansion reduces lung morbidity and healthcare utilization after open abdominal surgery. TRIAL REGISTRATION: ClinicalTrial.gov NCT04108130.


Asunto(s)
Anestesia , Enfermedades Pulmonares , Adulto , Humanos , Anestesia/efectos adversos , Pulmón/cirugía , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/prevención & control , Enfermedades Pulmonares/epidemiología , Estudios Multicéntricos como Asunto , Respiración con Presión Positiva/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Ensayos Clínicos Pragmáticos como Asunto
18.
Br J Anaesth ; 130(5): 507-510, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36931963

RESUMEN

Spin and fragility are common in randomised controlled trials published in anaesthesia journals. Staying with the facts and addressing only the primary endpoint in the conclusion of clinical research reports might help reduce spin. Routinely reporting the fragility index, in turn, could deliver information about robustness, enhancing the transparency of positive dichotomous results. It is in the best interest of clinical research that authors, reviewers, and journals come together to reduce spin and address the fragility of randomised controlled trials.


Asunto(s)
Anestesia , Anestesiología , Humanos , Anestesistas , Ensayos Clínicos Controlados Aleatorios como Asunto
20.
Eur J Anaesthesiol ; 40(7): 501-510, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-36809307

RESUMEN

BACKGROUND: Variable ventilation recruits alveoli in atelectatic lungs, but it is unknown how it compares with conventional recruitment manoeuvres. OBJECTIVES: To test whether mechanical ventilation with variable tidal volumes and conventional recruitment manoeuvres have comparable effects on lung function. DESIGN: Randomised crossover study. SETTING: University hospital research facility. ANIMALS: Eleven juvenile mechanically ventilated pigs with atelectasis created by saline lung lavage. INTERVENTIONS: Lung recruitment was performed using two strategies, both with an individualised optimal positive-end expiratory pressure (PEEP) associated with the best respiratory system elastance during a decremental PEEP trial: conventional recruitment manoeuvres (stepwise increase of PEEP) in pressure-controlled mode) followed by 50 min of volume-controlled ventilation (VCV) with constant tidal volume, and variable ventilation, consisting of 50 min of VCV with random variation in tidal volume. MAIN OUTCOME MEASURES: Before and 50 min after each recruitment manoeuvre strategy, lung aeration was assessed by computed tomography, and relative lung perfusion and ventilation (0% = dorsal, 100% = ventral) were determined by electrical impedance tomography. RESULTS: After 50 min, variable ventilation and stepwise recruitment manoeuvres decreased the relative mass of poorly and nonaerated lung tissue (percent lung mass: 35.3 ±â€Š6.2 versus 34.2 ±â€Š6.6, P  = 0.303); reduced poorly aerated lung mass compared with baseline (-3.5 ±â€Š4.0%, P  = 0.016, and -5.2 ±â€Š2.8%, P  < 0.001, respectively), and reduced nonaerated lung mass compared with baseline (-7.2 ±â€Š2.5%, P  < 0.001; and -4.7 ±â€Š2.8%, P  < 0.001 respectively), while the distribution of relative perfusion was barely affected (variable ventilation: -0.8 ±â€Š1.1%, P  = 0.044; stepwise recruitment manoeuvres: -0.4 ±â€Š0.9%, P  = 0.167). Compared with baseline, variable ventilation and stepwise recruitment manoeuvres increased Pa O 2 (172 ±â€Š85mmHg, P  = 0.001; and 213 ±â€Š73 mmHg, P  < 0.001, respectively), reduced Pa CO 2 (-9.6 ±â€Š8.1 mmHg, P  = 0.003; and -6.7 ±â€Š4.6 mmHg, P  < 0.001, respectively), and decreased elastance (-11.4 ±â€Š6.3 cmH 2 O, P  < 0.001; and -14.1 ±â€Š3.3 cmH 2 O, P  < 0.001, respectively). Mean arterial pressure decreased during stepwise recruitment manoeuvres (-24 ±â€Š8 mmHg, P  = 0.006), but not variable ventilation. CONCLUSION: In this model of lung atelectasis, variable ventilation and stepwise recruitment manoeuvres effectively recruited lungs, but only variable ventilation did not adversely affect haemodynamics. TRIAL REGISTRATION: This study was registered and approved by Landesdirektion Dresden, Germany (DD24-5131/354/64).


Asunto(s)
Pulmón , Atelectasia Pulmonar , Porcinos , Animales , Pulmón/diagnóstico por imagen , Atelectasia Pulmonar/terapia , Respiración Artificial/métodos , Respiración con Presión Positiva/métodos , Modelos Teóricos
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