Guidelines for inhaled sedation in the ICU.

INTRODUCTION AND OBJECTIVES: Sedation is used in intensive care units (ICU) to improve comfort and tolerance during mechanical ventilation, invasive interventions, and nursing care. In recent years, the use of inhalation anaesthetics for this purpose has increased. Our objective was to obtain and summarise the best evidence on inhaled sedation in adult patients in the ICU, and use this to help physicians choose the most appropriate approach in terms of the impact of sedation on clinical outcomes and the risk-benefit of the chosen strategy. METHODOLOGY: Given the overall lack of literature and scientific evidence on various aspects of inhaled sedation in the ICU, we decided to use a Delphi method to achieve consensus among a group of 17 expert panellists. The processes was conducted over a 12-month period between 2022 and 2023, and followed the recommendations of the CREDES guidelines. RESULTS: The results of the Delphi survey form the basis of these 39 recommendations - 23 with a strong consensus and 15 with a weak consensus. CONCLUSION: The use of inhaled sedation in the ICU is a reliable and appropriate option in a wide variety of clinical scenarios. However, there are numerous aspects of the technique that require further study.

Estudio de validación de los parámetros dinámicos de onda de pulso en cirugía de resección pulmonar / Validation study of the dynamic parameters of pulse wave in pulmonary resection surgery

INTRODUCCIÓN: En cirugía de resección pulmonar se recomienda la fluidoterapia restrictiva debido al riesgo de lesión pulmonar aguda. Por contra, esta recomendación aumenta el riesgo de hipoperfusión. La terapia guiada por objetivos permite individualizar el aporte de fluidos. El uso de parámetros dinámicos de respuesta a volumen no está validado durante la ventilación unipulmonar. El objetivo principal es la validación de los parámetros dinámicos, la variación de volumen sistólico (VVS) y la variación de presión de pulso (VPP) durante la cirugía de resección pulmonar como predictores de respuesta a fluidos tras la administración de cargas de volumen de 250ml de cristaloides, si IC<2,5ml/min/m2 y si VVS≥8% y/o VPP≥10%. MATERIAL Y MÉTODOS: Estudio piloto, prospectivo, observacional y unicéntrico. Se incluyeron 25 pacientes monitorizados con el sistema PiCCO durante la cirugía abierta de resección pulmonar con el paciente en posición de decúbito lateral, ventilación unipulmonar con VC: 6ml/kg y tórax abierto. Se recogieron variables hemodinámicas antes y después de la carga de volumen. Los resultados se clasificaron en dos grupos: respondedores a volumen (aumento de IC≥10% y/o VSI≥10% tras la carga de volumen) y los no respondedores (no aumento o aumento del IC<10% y/o VSI<10% tras la carga de volumen). Evaluamos la eficacia diagnóstica de VVS y VPP mediante el estudio del área bajo a curva (AUC) de las curvas ROC. RESULTADOS: En el análisis de curvas ROC, VVS y VPP no alcanzaron un valor discriminativo (AUCVVS: 0,47; AUCVPP: 0,50), a pesar de la disminución del valor umbral de VVS y de VPP para iniciar una sobrecarga de volumen durante la ventilación unipulmonar, en decúbito lateral y con el tórax abierto. CONCLUSIONES: Los resultados obtenidos muestran que los valores de los parámetros dinámicos de respuesta a volumen (VVS≥8% y VPP≥10%) no discriminan a los pacientes respondedores y a los no respondedores durante la cirugía de resección pulmonar abierta

INTRODUCTION: In lung resection surgery, restrictive fluid therapy is recommended due to the risk of acute lung injury. In contrast, this recommendation increases the risk of hypoperfusion. Guided fluid therapy allows individualization of fluid intake. The use of dynamic volume response parameters is not validated during one-lung ventilation. The main objective is the validation of dynamic parameters, stroke volume variation (SVV) and pulse pressure variation (PPV), during lung resection surgery as fluid response predictors, after the administration of 250ml crystalloid volume loads, if IC<2.5ml/min/m2 and if SVV≥8% and/or PPV≥10%. MATERIAL AND METHODS: Pilot, prospective, observational and single centre study. Twenty-five patients monitored with the PiCCO system were included during open lung resection surgery with the patient in a lateral position, one lung ventilation with tidal volume (TV): 6ml/kg and open chest. Hemodynamic variables were collected before and after volume loading. The results were classified into two groups: volume responders (increase IC≥10% and/or VSI≥10% after volume loading) and non-responders (no increase or increase IC<10% and/or VSI<10% after volume loading). We assess the diagnostic efficacy of SVV and PPV by analyzing the AUC (area under curve) in the ROC curves. RESULTS: In the analysis of ROC curves, SVV and PPV did not reach a discriminative value (AUCSVV: 0.47; AUCPPV: 0.50), despite the decrease in the threshold value of SVV and PPV to initiate an overload of volume during one-lung ventilation, in lateral position and open chest. CONCLUSIONS: The results obtained show that the values of the dynamic parameters of volume response (SVV≥8% and PPV≥10%) do not discriminate against responders patients and non-responders during open lung resection surgery

Validation study of the dynamic parameters of pulse wave in pulmonary resection surgery. / Estudio de validación de los parámetros dinámicos de onda de pulso en cirugía de resección pulmonar.

INTRODUCTION: In lung resection surgery, restrictive fluid therapy is recommended due to the risk of acute lung injury. In contrast, this recommendation increases the risk of hypoperfusion. Guided fluid therapy allows individualization of fluid intake. The use of dynamic volume response parameters is not validated during one-lung ventilation. The main objective is the validation of dynamic parameters, stroke volume variation (SVV) and pulse pressure variation (PPV), during lung resection surgery as fluid response predictors, after the administration of 250ml crystalloid volume loads, if IC<2.5ml/min/m2 and if SVV≥8% and/or PPV≥10%. MATERIAL AND METHODS: Pilot, prospective, observational and single centre study. Twenty-five patients monitored with the PiCCO system were included during open lung resection surgery with the patient in a lateral position, one lung ventilation with tidal volume (TV): 6ml/kg and open chest. Hemodynamic variables were collected before and after volume loading. The results were classified into two groups: volume responders (increase IC≥10% and/or VSI≥10% after volume loading) and non-responders (no increase or increase IC<10% and/or VSI<10% after volume loading). We assess the diagnostic efficacy of SVV and PPV by analyzing the AUC (area under curve) in the ROC curves. RESULTS: In the analysis of ROC curves, SVV and PPV did not reach a discriminative value (AUCSVV: 0.47; AUCPPV: 0.50), despite the decrease in the threshold value of SVV and PPV to initiate an overload of volume during one-lung ventilation, in lateral position and open chest. CONCLUSIONS: The results obtained show that the values of the dynamic parameters of volume response (SVV≥8% and PPV≥10%) do not discriminate against responders patients and non-responders during open lung resection surgery.

Economic evaluation of the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) from the national payer perspective: introduction of a new treatment to the patient journey. A simulation of three European countries.

Background: The aim of this study was to develop a spending predictor model to evaluate the direct costs associated with the management of ABSSSIs from the National health-care provider's perspective of Italy, Romania, and Spain. Methodology: A decision-analytic model was developed to evaluate the diagnostic and clinical pathways of hospitalized ABSSSI patients based on scientific guidelines and real-world data. A Standard of Care (SoC) scenario was compared with a dalbavancin scenario in which the patients could be discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases (i.e., hospital information system). A probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWA) were performed. Results: Overall, the model estimated an average annual number of patients with ABSSSIs of approximately 50,000 in Italy, Spain, and Romania. On average, the introduction of dalbavancin reduced the length of stay by 3.3 days per ABSSSI patient. From an economic perspective, dalbavancin did not incur any additional cost from the National Healthcare perspective, and the results were consistent among the countries. The PSA and OWA demonstrated the robustness of these results. Conclusion: This model represents a useful tool for policymakers by providing information regarding the economic and organizational consequences of an early discharge approach in ABSSSI management.

Hiperoxia perioperatoria: mitos y realidades / Perioperative hyperoxia: Myths and realities

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Individualized lung recruitment maneuver guided by pulse-oximetry in anesthetized patients undergoing laparoscopy: a feasibility study.

BACKGROUND: We conducted this study to test whether pulse-oximetry hemoglobin saturation (SpO2 ) can personalize the implementation of an open-lung approach during laparoscopy. Thirty patients with SpO2  ≥ 97% on room-air before anesthesia were studied. After anesthesia and capnoperitoneum the FIO2 was reduced to 0.21. Those patients whose SpO2 decreased below 97% - an indication of shunt related to atelectasis - completed the following phases: (1) First recruitment maneuver (RM), until reaching lung's opening pressure, defined as the inspiratory pressure level yielding a SpO2 ≥ 97%; (2) decremental positive end-expiratory (PEEP) titration trial until reaching lung's closing pressure defined as the PEEP level yielding a SpO2  < 97%; (3) second RM and, (4) ongoing ventilation with PEEP adjusted above the detected closing pressure. RESULTS: When breathing air, in 24 of 30 patients SpO2 was < 97%, PaO2 /FIO2  Ë‚ 53.3 kPa and negative end-expiratory transpulmonary pressure (PTP-EE ). The mean (SD) opening pressures were found at 40 (5) and 33 (4) cmH2 O during the first and second RM, respectively (P < 0.001; 95% CI: 3.2-7.7). The closing pressure was found at 11 (5) cmH2 O. This SpO2 -guided approach increased PTP-EE (from -6.4 to 1.2 cmH2 O, P < 0.001) and PaO2 /FIO2 (from 30.3 to 58.1 kPa, P < 0.001) while decreased driving pressure (from 18 to 10 cmH2 O, P < 0.001). SpO2 discriminated the lung's opening and closing pressures with accuracy taking the reference parameter PTP-EE (area under the receiver-operating-curve of 0.89, 95% CI: 0.80-0.99). CONCLUSION: The non-invasive SpO2 monitoring can help to individualize an open-lung approach, including all involved steps, from the identification of those patients who can benefit from recruitment, the identification of opening and closing pressures to the subsequent monitoring of an open-lung condition.

High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society advise evaluating autoantibody positivity in first-degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the disease. The aim of this study was to determine the prevalence of beta-cell autoimmunity in FDRs of T1DM patients in Sardinia. METHODS: A total of 188 Sardinian families were recruited in collaboration between diabetes and pediatric units of university and district hospitals in Sardinia. The recruitment involved 188 patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies (Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43 Aabs-positive FDR. RESULTS: The prevalence of Aabs (any type of autoantibody, single or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53) were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55% (4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of HLA-DR and DQ loci showed that 89% of FDR carried moderate- to high-risk genotypes, with only 5 FDR with low-risk genotypes. CONCLUSIONS: The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.

Integridad renal y hepática tras la sedación prolongada con sevoflurano administrado a través del dispositivo AnaConDa(R): comparación con la sedación intravenosa con propofol en modelo animal / Renal and hepatic integrity in long-term sevoflurane sedation using the anesthetic conserving device: a comparison with intravenous propofol sedation in an animal model

Introducción: En la actualidad la sedación de los pacientes críticos se realiza mediante agentes intravenosos. La utilización de agentes inhalatorios, como alternativa a la sedación intravenosa, se encuentra limitada por su potencial riesgo de toxicidad. El incremento de los niveles de fluoruros inorgánicos, tras su metabolización, ha sido considerado potencialmente nefrotóxico. Por otro lado, la afectación hepática después de la administración prolongada de sevoflurano no ha sido estudiada. Se evaluó la potencial toxicidad renal y hepática causada por la administración prolongada (72 h) de sevoflurano. Métodos: Estudio experimental, prospectivo, aleatorizado y controlado. Veintidós animales cerdas de la raza Landrace x Large-White fueron asignadas aleatoriamente a 2 grupos en función del régimen de sedación administrado (P: propofol por vía intravenosa; o S: sevoflurano inhalado a través del sistema AnaConDa(R), endtidal 2,5%). El grupo P se mantuvo sedado durante 108 h con propofol. Al grupo S se le administró sevoflurano durante 72 h, cambiando a propofol durante las 36 h restantes, con el objetivo de observar la cinética de los fluoruros plasmáticos tras la interrupción del sevoflurano. Se midieron la creatinina plasmática como variable principal, las concentraciones de fluoruros inorgánicos y otras variables de función renal, hepática y cardiorrespiratoria. Resultados: Ambos grupos de animales fueron comparables en el momento basal. No hubo diferencias significativas entre ambos grupos en cuanto a los valores de creatinina plasmática, urea y aclaramiento de creatinina. Los niveles de fluoruros fueron significativamente mayores en el grupo de sevoflurano. No encontramos una correlación entre las cifras de fluoruros inorgánicos y los valores de creatinina plasmática. Tampoco se observaron diferencias significativas en los parámetros de función hepática. Las variables hemodinámicas, respiratorias y gasométricas fueron comparables entre los grupos. Conclusiones: La sedación de larga duración no afecta a la función renal ni hepática, independientemente del agente utilizado (AU)

Introduction: Critically ill patients are sedated with intravenous agents because the use of inhaled agents is limited by their potential risk of toxicity. Increasing levels of inorganic fluorides after the metabolism of these agents have been considered potentially nephrotoxic. However, hepatic involvement after prolonged administration of sevoflurane has not yet been studied. The present study evaluated the potential renal and hepatic toxicity caused by prolonged administration (72 h) of sevoflurane. Methods: For this experimental, prospective, randomized, controlled trial, 22 Landrace x Large-White female pigs were randomly assigned to two groups: intravenous propofol (P) or inhaled sevoflurane via the AnaConDa(TM) device (S, end-tidal 2.5 vol%). The P group remained sedated for 108 h with propofol. In the S group, sevoflurane was administered for 72 h and then changed to propofol for the remaining 36 h in order to observe the kinetics of fluoride after discontinuation of sevoflurane. Serum creatinine was the primary outcome variable, but inorganic fluoride concentrations and other renal, hepatic, and cardiorespiratory variables were also measured. Results: Both groups of animals were comparable at baseline. No differences were found between the two groups for plasma creatinine and urea or creatinine clearance throughout the study. Fluoride levels were significantly higher in the sevoflurane group. No correlation was found between inorganic fluoride and serum creatinine values. No significant differences were observed for hepatic function. Hemodynamic, respiratory, and blood gas variables were comparable between the groups. Conclusions: Long-term sedation with sevoflurane using AnaConDa(TM) or propofol does not negatively affect renal or hepatic function (AU)

Renal and hepatic integrity in long-term sevoflurane sedation using the anesthetic conserving device: a comparison with intravenous propofol sedation in an animal model.

INTRODUCTION: Critically ill patients are sedated with intravenous agents because the use of inhaled agents is limited by their potential risk of toxicity. Increasing levels of inorganic fluorides after the metabolism of these agents have been considered potentially nephrotoxic. However, hepatic involvement after prolonged administration of sevoflurane has not yet been studied. The present study evaluated the potential renal and hepatic toxicity caused by prolonged administration (72h) of sevoflurane. METHODS: For this experimental, prospective, randomized, controlled trial, 22 Landrace x Large-White female pigs were randomly assigned to two groups: intravenous propofol (P) or inhaled sevoflurane via the AnaConDa™ device (S, end-tidal 2.5 vol%). The P group remained sedated for 108h with propofol. In the S group, sevoflurane was administered for 72h and then changed to propofol for the remaining 36h in order to observe the kinetics of fluoride after discontinuation of sevoflurane. Serum creatinine was the primary outcome variable, but inorganic fluoride concentrations and other renal, hepatic, and cardiorespiratory variables were also measured. RESULTS: Both groups of animals were comparable at baseline. No differences were found between the two groups for plasma creatinine and urea or creatinine clearance throughout the study. Fluoride levels were significantly higher in the sevoflurane group. No correlation was found between inorganic fluoride and serum creatinine values. No significant differences were observed for hepatic function. Hemodynamic, respiratory, and blood gas variables were comparable between the groups. CONCLUSIONS: Long-term sedation with sevoflurane using AnaConDa™ or propofol does not negatively affect renal or hepatic function.

Cost of poor adherence to anti-hypertensive therapy in five European countries.

The financial burden for EU health systems associated with cardiovascular disease (CV) has been estimated to be nearly €110 billion in 2006, corresponding to 10% of total healthcare expenditure across EU or a mean €223 annual cost per capita. The main purpose of this study is to estimate the costs related to hypertension and the economic impact of increasing adherence to anti-hypertensive therapy in five European countries (Italy, Germany, France, Spain and England). A probabilistic prevalence-based decision tree model was developed to estimate the direct costs of CV related to hypertension (CV defined as: stroke, heart attack, heart failure) in five European countries. Our model considered adherence to hypertension treatment as a main driver of blood pressure (BP) control (BP < 140/90 mmHg). Relative risk of CV, based on controlled or uncontrolled BP group, was estimated from the Framingham Heart Study and national review data. Prevalence and cost data were estimated from national literature reviews. A national payer (NP) perspective for 10 years was considered. Probabilistic sensitivity analysis was performed in order to evaluate uncertainty around the results (given as 95% confidence intervals). The model estimated a total of 8.6 million (1.4 in Italy, 3.3 in Germany, 1.2 in Spain, 1.8 in France and 0.9 in England) CV events related to hypertension over the 10-year time horizon. Increasing the adherence rate to anti-hypertensive therapy to 70% (baseline value is different for each country) would lead to 82,235 fewer CV events (24,058 in Italy, 7,870 in Germany, 18,870 in Spain, 24,855 in France and 6,553 in England). From the NP perspective, the direct cost associated with hypertension was estimated to be 51.3 billion (8.1 in Italy, 17.1 in Germany, 12.2 in Spain, 8.8 in France and 5.0 in England). Increasing adherence to anti-hypertensive therapy to 70% would save a total of 332 million (CI 95%: €319-346 million) from the NPs perspective. This study is the first attempt to estimate the economic impact of non-adherence amongst patients with diagnosed hypertension in Europe, using data from five European countries (Italy, France, Germany, Spain and England).

Airway pressure curve: a good tool to measure neural inspiratory time?

BACKGROUND: Considerable asynchrony during pressure-support ventilation has been reported. While the beginning of active inspiration is usually identifiable in the airway pressure (Paw) curve (the inspiratory trigger), there is still a need for accurate, non-invasive methods to identify the end of inspiration. To test the hypothesis that inspiration, particularly the end of inspiration, can be estimated from the Paw curve, we compared indirect measurements based on Paw with simultaneous direct electromyography of the diaphragm (EMGdi). METHODS: We prospectively studied 10 patients during the weaning period after cardiac surgery. Inspiratory pressure support was set at 20, 15, 10, and 5 cm H(2)O; 25 respiratory cycles were analyzed at each pressure level. Recording of the electromyogram was obtained with electrodes inserted into the diaphragm during surgery. RESULTS: The start and end of inspiration were identified in the Paw curve in 99% and 98% of the 1000 cycles analyzed, respectively, and were coincident with the electromyogram in 62% and 53% of the cycles, respectively. The inspiratory time estimated from the Paw curve was well correlated (r=0.94, P<0.0001) with the electromyogram. CONCLUSION: The end of neural inspiration (EMGdi) can be easily and with little error recognized from the Paw curve alone in patients with normal ventilatory mechanics who receive pressure-support ventilation.

Aumento de presión en la vía aérea durante la ventilación mecánica: más allá del broncoespasmo / No disponible

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Offspring from endogamic vs. exogamic matings: Absence of anthropometric differences among Sardinian children (Italy).

This study evaluates possible differences in body dimensions among children from matings of different exogamy levels. The cross-sectional sample consisted of 867 children, 435 males, and 432 females, 6-10 years old, attending elementary schools in the metropolitan area of Cagliari, the capital of Sardinia (Italy). The children were divided into two groups according to the level of exogamy. The first group consisted of children of parents born in the same Sardinian municipality and was considered endogamous sensu stricto. The second group included children of parents born in municipalities from different Sardinian linguistic domains and was considered exogamous. The Mann-Whitney test did not reveal significant differences between the two groups of children in the mean rank values of the 36 anthropometric variables considered, with the exception of cephalic circumference in males and chest depth in females. In particular, there were no significant differences for anthropometric variables considered to be indirect indicators of nutritional status: sum of skinfolds, waist/hip ratio, body mass index, total upper arm area, upper arm muscle area, and upper arm fat area. The results indicate that Sardinian children from marriages of different exogamy levels do not differ in body dimensions if they grow up with similar nutritional and socioeconomic conditions.

Effects of prone position on alveolar dead space and gas exchange during general anaesthesia in surgery of long duration.

BACKGROUND AND OBJECTIVE: We investigated the effects of prone position on respiratory dead space and gas exchange in 14 anaesthetized healthy patients undergoing elective posterior spinal surgery of more than 3 h of duration. METHODS: The patients received a total intravenous anaesthetic with propofol/remifentanil/cisatracurium. They were ventilated at a tidal volume of 8-10 mL kg(-1), zero positive end-expiratory pressure and an inspired oxygen fraction of 0.4. Physiological, airway and alveolar dead spaces were calculated by analysis of the volumetric capnography waveform. Measurements were made in supine position (20 min after the beginning of mechanical ventilation) and 30, 120 and 180 min after turning to prone position. RESULTS: We found that the alveolar dead space/tidal volume ratio did not change. PaO(2)/F(i)O(2) increased, although not statistically significantly. Dynamic compliance was reduced due to a reduction in tidal volume and an increase in plateau pressure. CONCLUSIONS: Patients undergoing surgery in prone position for a duration of 3 h under general anaesthesia including muscle relaxation and mechanical ventilation without positive end-expiratory pressure have stable haemodynamics and no significant changes in the alveolar dead space to tidal volume ratio. Oxygenation tended to improve.

[Measurement of cardiac output after cardiac surgery: validation of a partial carbon dioxide rebreathing (NICO) system in comparison with continuous thermodilution with a pulmonary artery catheter]. / Medición del gasto cardíaco en el postoperatorio de cirugía cardiaca: validez de la reinhalación parcial de CO2 (NICO) frente a la termodilución continua mediante catéter de arteria pulmonar.

UNLABELLED: Cardiac output is usually monitored with a pulmonary artery catheter. However, because that method is not free of risk, devices have been designed in recent years to measure cardiac output in a way that is minimally invasive or fully noninvasive. Among such devices is the NICO monitor, which is based on a modified Fick equation (partial CO2 rebreathing). OBJECTIVE: To compare the accuracy of cardiac output measurements from the NICO monitor to measurements obtained by continuous thermodilution with a pulmonary artery catheter. MATERIAL AND METHODS: A nonprobabilistic, consecutive sample of 20 patients was enrolled in the early postoperative period after elective cardiac surgery (coronary or valve procedures) in the recovery ward. Seven measurements of cardiac output were taken simultaneously with each method in each patient. RESULTS AND CONCLUSIONS: Cardiac output estimated by the partial CO2 rebreathing method was lower than the measurement obtained by the pulmonary artery catheter. The percentage error between the 2 methods was 37%, indicating that the NICO monitor can not substitute for the traditional method. The better correlation found between normal-to-low cardiac output values and the absence of side effects of using the NICO method suggest that it might be indicated for detecting low cardiac output after cardiac surgery, especially when the risk-benefit ratio does not favor using a pulmonary artery catheter.