The impact of norepinephrine dose reporting heterogeneity on mortality prediction in septic shock patients.

BACKGROUND: Norepinephrine (NE) is a cornerstone drug in the management of septic shock, with its dose being used clinically as a marker of disease severity and as mortality predictor. However, variations in NE dose reporting either as salt formulations or base molecule may lead to misinterpretation of mortality risks and hinder the process of care. METHODS: We conducted a retrospective analysis of the MIMIC-IV database to assess the impact of NE dose reporting heterogeneity on mortality prediction in a cohort of septic shock patients. NE doses were converted from the base molecule to equivalent salt doses, and their ability to predict 28-day mortality at common severity dose cut-offs was compared. RESULTS: 4086 eligible patients with septic shock were identified, with a median age of 68 [57-78] years, an admission SOFA score of 7 [6-10], and lactate at diagnosis of 3.2 [2.4-5.1] mmol/L. Median peak NE dose at day 1 was 0.24 [0.12-0.42] µg/kg/min, with a 28-day mortality of 39.3%. The NE dose showed significant heterogeneity in mortality prediction depending on which formulation was reported, with doses reported as bitartrate and tartrate presenting 65 (95% CI 79-43)% and 67 (95% CI 80-47)% lower ORs than base molecule, respectively. This divergence in prediction widened at increasing NE doses. When using a 1 µg/kg/min threshold, predicted mortality was 54 (95% CI 52-56)% and 83 (95% CI 80-87)% for tartrate formulation and base molecule, respectively. CONCLUSIONS: Heterogeneous reporting of NE doses significantly affects mortality prediction in septic shock. Standardizing NE dose reporting as base molecule could enhance risk stratification and improve processes of care. These findings underscore the importance of consistent NE dose reporting practices in critical care settings.

Differential Cardiac Responses after Passive Leg Raising.

This study retrospectively examined the hemodynamic effects of passive leg raising (PLR) in mechanically ventilated patients during fluid removal before spontaneous breathing trials. In previous studies, we noticed varying cardiac responses after PLR completion, particularly in positive tests. Using a bioreactance monitor, we recorded and analyzed hemodynamic parameters, including stroke volume and cardiac index (CI), before and after PLR in post-acute ICU patients. We included 27 patients who underwent 60 PLR procedures. In preload-unresponsive patients, no significant CI changes were observed (CI_t-6 = 3.7 [2.6; 4.7] mL/min/m2 vs. CI_t9 = 3.3 [2.5; 3.4] mL/min/m2; p = 0.306), while in preload-responsive patients, two distinct CI response types to PLR were identified: a transient peak with immediate return to baseline (CI_t-6 = 2.7 [2.5; 3.1] mL/min/m2 vs. 3.3 [2.6; 3.8] L/min/m2; p = 0.119) and a sustained CI elevation lasting beyond the PLR maneuver (CI_t-6 = 2.8 [2.3; 2.9] L/min/m2 vs. 3.3 [2.8; 3.9] ml/min/m2; p = 0.034). The latter was particularly noted when ΔCI during PLR exceeded 25%. Our findings suggest that in certain preload-responsive patients, PLR can induce a more sustained increase in CI, indicating a possible persistent hemodynamic effect. This effect could be due to a combination of autotransfusion and sympathetic activation affecting venous return and vascular tone. Further research in larger cohorts and more comprehensive hemodynamic assessments are warranted to validate these observations and elucidate the possible underlying mechanisms.The Fluid unLoading On Weaning (FLOW) study was prospectively registered under the ID NCT04496583 on 2020-07-29 at ClinicalTrials.gov.

Dynamic changes of hepatic vein Doppler velocities predict preload responsiveness in mechanically ventilated critically ill patients.

BACKGROUND: Assessment of dynamic parameters to guide fluid administration is one of the mainstays of current resuscitation strategies. Each test has its own limitations, but passive leg raising (PLR) has emerged as one of the most versatile preload responsiveness tests. However, it requires real-time cardiac output (CO) measurement either through advanced monitoring devices, which are not routinely available, or echocardiography, which is not always feasible. Analysis of the hepatic vein Doppler waveform change, a simpler ultrasound-based assessment, during a dynamic test such as PLR could be useful in predicting preload responsiveness. The objective of this study was to assess the diagnostic accuracy of hepatic vein Doppler S and D-wave velocities during PLR as a predictor of preload responsiveness. METHODS: Prospective observational study conducted in two medical-surgical ICUs in Chile. Patients in circulatory failure and connected to controlled mechanical ventilation were included from August to December 2023. A baseline ultrasound assessment of cardiac function was performed. Then, simultaneously, ultrasound measurements of hepatic vein Doppler S and D waves and cardiac output by continuous pulse contour analysis device were performed during a PLR maneuver. RESULTS: Thirty-seven patients were analyzed. 63% of the patients were preload responsive defined by a 10% increase in CO after passive leg raising. A 20% increase in the maximum S wave velocity after PLR showed the best diagnostic accuracy with a sensitivity of 69.6% (49.1-84.4) and specificity of 92.8 (68.5-99.6) to detect preload responsiveness, with an area under curve of receiving operator characteristic (AUC-ROC) of 0.82 ± 0.07 (p = 0.001 vs. AUC-ROC of 0.5). D-wave velocities showed worse diagnostic accuracy. CONCLUSIONS: Hepatic vein Doppler assessment emerges as a novel complementary technique with adequate predictive capacity to identify preload responsiveness in patients in mechanical ventilation and circulatory failure. This technique could become valuable in scenarios of basic hemodynamic monitoring and when echocardiography is not feasible. Future studies should confirm these results.

Fluid Responsiveness Is Associated with Successful Weaning after Liver Transplant Surgery.

A positive fluid balance may evolve to fluid overload and associate with organ dysfunctions, weaning difficulties, and increased mortality in ICU patients. We explored whether individualized fluid management, assessing fluid responsiveness via a passive leg-raising maneuver (PLR) before a spontaneous breathing trial (SBT), is associated with less extubation failure in ventilated patients with a high fluid balance admitted to the ICU after liver transplantation (LT). We recruited 15 LT patients in 2023. Their postoperative fluid balance was +4476 {3697, 5722} mL. PLR maneuvers were conducted upon ICU admission (T1) and pre SBT (T2). Cardiac index (CI) changes were recorded before and after each SBT (T3). Seven patients were fluid-responsive at T1, and twelve were responsive at T2. No significant differences occurred in hemodynamic, respiratory, and perfusion parameters between the fluid-responsive and fluid-unresponsive patients at any time. Fluid-responsive patients at T1 and T2 increased their CI during SBT from 3.1 {2.8, 3.7} to 3.7 {3.4, 4.1} mL/min/m2 (p = 0.045). All fluid-responsive patients at T2 were extubated after the SBTs and consolidated extubation. Two out of three of the fluid-unresponsive patients experienced weaning difficulties. We concluded that fluid-responsive patients post LT may start weaning earlier and achieve successful extubation despite a high postoperative fluid balance. This highlights the profound impact of personalized assessments of cardiovascular state on critical surgical patients.

Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study.

BACKGROUND: Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. METHODS: Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80-85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). RESULTS: CRT decreased significantly with both tests (from 5 [3.5-7.6] to 4 [2.4-5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3-5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. CONCLUSIONS: Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.

Consistency of data reporting in fluid responsiveness studies in the critically ill setting: the CODEFIRE consensus from the Cardiovascular Dynamic section of the European Society of Intensive Care Medicine.

PURPOSE: To provide consensus recommendations regarding hemodynamic data reporting in studies investigating fluid responsiveness and fluid challenge (FC) use in the intensive care unit (ICU). METHODS: The Executive Committee of the European Society of Intensive Care Medicine (ESICM) commissioned and supervised the project. A panel of 18 international experts and a methodologist identified main domains and items from a systematic literature, plus 2 ancillary domains. A three-step Delphi process based on an iterative approach was used to obtain the final consensus. In the Delphi 1 and 2, the items were selected with strong (≥ 80% of votes) or week agreement (70-80% of votes), while the Delphi 3 generated recommended (≥ 90% of votes) or suggested (80-90% of votes) items (RI and SI, respectively). RESULTS: We identified 5 main domains initially including 117 items and the consensus finally resulted in 52 recommendations or suggestions: 18 RIs and 2 SIs statements were obtained for the domain "ICU admission", 11 RIs and 1 SI for the domain "mechanical ventilation", 5 RIs for the domain "reason for giving a FC", 8 RIs for the domain pre- and post-FC "hemodynamic data", and 7 RIs for the domain "pre-FC infused drugs". We had no consensus on the use of echocardiography, strong agreement regarding the volume (4 ml/kg) and the reference variable (cardiac output), while weak on administration rate (within 10 min) of FC in this setting. CONCLUSION: This consensus found 5 main domains and provided 52 recommendations for data reporting in studies investigating fluid responsiveness in ICU patients.

Coexistence of a fluid responsive state and venous congestion signals in critically ill patients: a multicenter observational proof-of-concept study.

BACKGROUND: Current recommendations support guiding fluid resuscitation through the assessment of fluid responsiveness. Recently, the concept of fluid tolerance and the prevention of venous congestion (VC) have emerged as relevant aspects to be considered to avoid potentially deleterious side effects of fluid resuscitation. However, there is paucity of data on the relationship of fluid responsiveness and VC. This study aims to compare the prevalence of venous congestion in fluid responsive and fluid unresponsive critically ill patients after intensive care (ICU) admission. METHODS: Multicenter, prospective cross-sectional observational study conducted in three medical-surgical ICUs in Chile. Consecutive mechanically ventilated patients that required vasopressors and admitted < 24 h to ICU were included between November 2022 and June 2023. Patients were assessed simultaneously for fluid responsiveness and VC at a single timepoint. Fluid responsiveness status, VC signals such as central venous pressure, estimation of left ventricular filling pressures, lung, and abdominal ultrasound congestion indexes and relevant clinical data were collected. RESULTS: Ninety patients were included. Median age was 63 [45-71] years old, and median SOFA score was 9 [7-11]. Thirty-eight percent of the patients were fluid responsive (FR+), while 62% were fluid unresponsive (FR-). The most prevalent diagnosis was sepsis (41%) followed by respiratory failure (22%). The prevalence of at least one VC signal was not significantly different between FR+ and FR- groups (53% vs. 57%, p = 0.69), as well as the proportion of patients with 2 or 3 VC signals (15% vs. 21%, p = 0.4). We found no association between fluid balance, CRT status, or diagnostic group and the presence of VC signals. CONCLUSIONS: Venous congestion signals were prevalent in both fluid responsive and unresponsive critically ill patients. The presence of venous congestion was not associated with fluid balance or diagnostic group. Further studies should assess the clinical relevance of these results and their potential impact on resuscitation and monitoring practices.

Geo-economic Influence on the Effect of Fluid Volume for Sepsis Resuscitation: A Meta-Analysis.

Rationale: Sepsis management relies on fluid resuscitation avoiding fluid overload and its related organ congestion. Objectives: To explore the influence of country income group on risk-benefit balance of fluid management strategies in sepsis. Methods: We searched e-databases for all randomized controlled trials on fluid resuscitation in patients with sepsis or septic shock up to January 2023, excluding studies on hypertonic fluids, colloids, and depletion-based interventions. The effect of fluid strategies (higher versus lower volumes) on mortality was analyzed per income group (i.e., low- and middle-income countries [LMICs] or high-income countries [HICs]). Measurements and Main Results: Twenty-nine studies (11,798 patients) were included in the meta-analysis. There was a numerically higher mortality in studies of LMICs as compared with those of HICs: median, 37% (interquartile range [IQR]: 26-41) versus 29% (IQR: 17-38; P = 0.06). Income group significantly interacted with the effect of fluid volume on mortality: Higher fluid volume was associated with higher mortality in LMICs but not in HICs: odds ratio (OR), 1.47; 95% confidence interval (95% CI): 1.14-1.90 versus 1.00 (95% CI: 0.87-1.16), P = 0.01 for subgroup differences. Higher fluid volume was associated with increased need for mechanical ventilation in LMICs (OR, 1.24 [95% CI: 1.08-1.43]) but not in HICs (OR, 1.02 [95% CI: 0.80-1.29]). Self-reported access to mechanical ventilation also significantly influenced the effect of fluid volume on mortality, which increased with higher volumes only in settings with limited access to mechanical ventilation (OR: 1.45 [95% CI: 1.09-1.93] vs. 1.09 [95% CI: 0.93-1.28], P = 0.02 for subgroup differences). Conclusions: In sepsis trials, the effect of fluid resuscitation approach differed by setting, with higher volume of fluid resuscitation associated with increased mortality in LMICs and in settings with restricted access to mechanical ventilation. The precise reason for these differences is unclear and may be attributable in part to resource constraints, participant variation between trials, or other unmeasured factors.

Ressuscitação direcionada ao tempo de enchimento capilar baseada em fenótipo hemodinâmico no choque séptico precoce: protocolo de estudo do ensaio clínico randomizado ANDROMEDA-SHOCK-2 / Hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial study protocol

RESUMO Introdução: A reversão precoce da hipoperfusão tecidual induzida é essencial para a sobrevida no choque séptico. No entanto, falta consenso sobre a melhor estratégia de ressuscitação inicial, uma vez que intervenções destinadas a toda a população com choque séptico podem produzir administração desnecessária de líquidos. Este artigo relata a justificativa, o delineamento e o plano de análise do estudo ANDROMEDA-2, que visa determinar se uma estratégia guiada por perfusão periférica, que consiste na ressuscitação guiada pelo tempo de enchimento capilar com base em fenótipos clínicos e hemodinâmicos, está associada a uma diminuição no desfecho composto de mortalidade, tempo até a interrupção ao suporte de órgãos e tempo de internação em comparação com o atendimento padrão em pacientes com choque séptico precoce (< 4 horas do diagnóstico). Metódos: O estudo ANDROMEDA-2 é um ensaio clínico randomizado controlado multinacional e multicêntrico. No grupo de intervenção, o tempo de enchimento capilar será medido a cada hora, durante 6 horas. Se estiver anormal, os pacientes serão alocados em um algoritmo, começando com a avaliação da pressão de pulso. Pacientes com pressão de pulso inferior a 40mmHg serão testados quanto à capacidade de resposta a líquidos e receberão líquidos de acordo. Em pacientes com pressão de pulso > 40mmHg, norepinefrina será titulada para manter a pressão arterial diastólica > 50mmHg. Os pacientes que não normalizarem o tempo de enchimento capilar após as etapas anteriores serão submetidos à ecocardiografia de cuidados intensivos para avaliação da disfunção cardíaca e posterior manejo. Por fim, serão realizados testes com vasopressores e inodilatadores para otimizar ainda mais a perfusão. Um tamanho de amostra de 1.500 pacientes fornecerá 88% de poder para demonstrar a superioridade da estratégia direcionada ao tempo de enchimento capilar. Conclusão: Se for demonstrado que o direcionamento ao tempo de enchimento capilar é uma estratégia melhor, os processos de atendimento na ressuscitação do choque séptico podem ser otimizados com ferramentas usadas à beira do leito.

ABSTRACT Background: Early reversion of sepsis-induced tissue hypoperfusion is essential for survival in septic shock. However, consensus regarding the best initial resuscitation strategy is lacking given that interventions designed for the entire population with septic shock might produce unnecessary fluid administration. This article reports the rationale, study design and analysis plan of the ANDROMEDA-2 study, which aims to determine whether a peripheral perfusion-guided strategy consisting of capillary refill time-targeted resuscitation based on clinical and hemodynamic phenotypes is associated with a decrease in a composite outcome of mortality, time to organ support cessation, and hospital length of stay compared to standard care in patients with early (< 4 hours of diagnosis) septic shock. Methods: The ANDROMEDA-2 study is a multicenter, multinational randomized controlled trial. In the intervention group, capillary refill time will be measured hourly for 6 hours. If abnormal, patients will enter an algorithm starting with pulse pressure assessment. Patients with pulse pressure less than 40mmHg will be tested for fluid responsiveness and receive fluids accordingly. In patients with pulse pressure > 40mmHg, norepinephrine will be titrated to maintain diastolic arterial pressure > 50mmHg. Patients who fail to normalize capillary refill time after the previous steps will be subjected to critical care echocardiography for cardiac dysfunction evaluation and subsequent management. Finally, vasopressor and inodilator tests will be performed to further optimize perfusion. A sample size of 1,500 patients will provide 88% power to demonstrate superiority of the capillary refill time-targeted strategy. Conclusions: If hemodynamic phenotype-based, capillary refill time-targeted resuscitation demonstrates to be a superior strategy, care processes in septic shock resuscitation can be optimized with bedside tools.

Plano de análise estatística para o estudo do tratamento precoce baseado em metas com utilização de uma visão fisiológica holística - estudo ANDROMEDA-SHOCK: um estudo randomizado e controlado / Statistical analysis plan for early goal-directed therapy using a physiological holistic view - the ANDROMEDA-SHOCK: a randomized controlled trial

RESUMO Fundamentação: O estudo ANDROMEDA-SHOCK é um estudo internacional, multicêntrico, randomizado e controlado comparando ressuscitação guiada pela perfusão periférica com ressuscitação guiada pelo lactato em pacientes com choque séptico, com a finalidade de testar a hipótese de que a ressuscitação guiada pela perfusão periférica associa-se a menor morbidade e mortalidade. Objetivo: Relatar o plano de análise estatística para o estudo ANDROMEDA-SHOCK. Métodos: Descrevemos o delineamento do estudo, os objetivos primário e secundários, pacientes, métodos de randomização, intervenções, desfechos e tamanho da amostra. Descrevemos nossos planos de análise estatística para os desfechos primários, secundários e terciários. Também descrevemos as análises de subgrupos e sensibilidade. Finalmente, fornecemos detalhes para a apresentação dos resultados, inclusive modelos de tabelas para apresentar as características basais, a evolução das variáveis de hemodinâmica e perfusão, e os efeitos dos tratamentos nos desfechos. Conclusão: Segundo as melhores práticas de pesquisa, relatamos nosso plano de análise estatística e plano de gestão de dados antes do fechamento da base de dados e do início da análise dos dados. Nossa expectativa é que este procedimento previna a ocorrência de vieses na análise e incremente a utilidade dos resultados relatados.

ABSTRACT Background: ANDROMEDA-SHOCK is an international, multicenter, randomized controlled trial comparing peripheral perfusion-targeted resuscitation to lactate-targeted resuscitation in patients with septic shock in order to test the hypothesis that resuscitation targeting peripheral perfusion will be associated with lower morbidity and mortality. Objective: To report the statistical analysis plan for the ANDROMEDA-SHOCK trial. Methods: We describe the trial design, primary and secondary objectives, patients, methods of randomization, interventions, outcomes, and sample size. We describe our planned statistical analysis for the primary, secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables showing baseline characteristics, the evolution of hemodynamic and perfusion variables, and the effects of treatments on outcomes. Conclusion: According to the best trial practice, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this procedure will prevent analysis bias and enhance the utility of the reported results.

Evaluación de la microcirculación con sidestream dark field (SDF) Microscan® como método de monitorización en microcirugía en modelo porcino / Microcirculation assessment with sidestream dark field (SDF) Microscan® as flap monitoring method in microsurgery in a porcine model

Objetivo: Determinar la factibilidad de la monitorización en microcirugía por medio de la evaluación no invasiva de la microcirculación con sidestream dark field (SDF) y compararla con otros métodos. Materiales y métodos: Estudio experimental. En 8 cerdos se elevó colgajo pectoral y se disecó pedículo. Se llevó a cabo una instalación sucesiva de dispositivos cutáneos para la evaluación de la microcirculación: SDF para evaluar flujo, y near infrared spectroscopy (NIRS) para evaluar saturación de O2 (SatO2). Posteriormente se evaluó la oclusión venosa, arterial y total con pinzamiento durante 180 s. Resultados: SDF en oclusión venosa: disminución del flujo: 51 s (59-62); SDF en oclusión arterial: disminución del flujo: 3 s (1-5); SDF en oclusión vascular total: disminución del flujo: 3,5 s (2-5). NIRS en oclusión venosa: disminución de la SatO2:15,2 ± 5,3%; NIRS en oclusión arterial: disminución de la SatO2 23,9 ± 13,8%; NIRS en oclusión vascular total: disminución de la SatO2 23,85 ± 13,9%. Doppler en oclusión venosa: no desapareció; Doppler en oclusión arterial y oclusión vascular total: desapareció a los 2 s. En cada una de las mediciones, los cambios clínicos fueron más tardíos que los observados con SDF. Conclusión: Es factible la monitorización en microcirugía por medio de la evaluación de la microcirculación con Microscan®. Este método permite realizar el diagnóstico de oclusión vascular más tempranamente que con NIRS y evaluación clínica.

Aim: Determine the feasibility of using SDF Microscan® as a non-invasive method for monitoring free flap microcirculation, and compare it to other methods. Materials and methods: Experimental study. In 8 pigs a pectoral myocutaneous flap was raised. Microcirculation was evaluated using: SDF Microscan®, near infrared spectroscopy (NIRS), clinical examination and Doppler. Venous, arterial and total occlusion was performed by clamping the vascular pedicle. Mean time to blood flow impairment diagnosis was measured. Results: SDF in venous occlusion: reduced microcirculatory flow index at: 51 s (59-62). SDF in arterial occlusion: reduced microcirculatory flow index at: 3 s (1-5). SDF in total vascular occlusion: reduced microcirculatory flow index at: 3.5 s (2-5). NIRS in venous occlusion: SatO2 decrease was 15.2 ± 5.3%. NIRS in arterial occlusion: SatO2 decrease was 23.9 ± 13.8%. NIRS in total vascular occlusion: SatO2 decrease was 23.85 ± 13.9%. Doppler in venous occlusion: The signal did not disappear. Doppler arterial and total vascular occlusion disappears at 2 s. The clinical changes were later than SDF. Conclusion: Microcirculation monitoring is feasible using SDF Microscan® in a pig model. This method allows to detect blood flow disruption earlier than NIRS and clinical evaluation.

Pressão expiratória final positiva aumenta o estiramento em pacientes com LPA/SDRA / Positive end-expiratory pressure increases strain in patients with ALI/ARDS

OBJETIVO: O objetivo deste estudo foi avaliar os efeitos da pressão expiratória final positiva no estiramento, recrutamento e recrutamento e desrecrutamento cíclico avaliados por tomografia computadorizada pulmonar em pacientes com lesão pulmonar aguda/síndrome do desconforto respiratório agudo. MÉTODOS: Trata-se de um estudo aberto, controlado, não randomizado, de intervenção, em pacientes com lesão pulmonar aguda/síndrome do desconforto respiratório agudo. Foram realizados cortes simples de tomografia computadorizada durante pausas inspiratórias e expiratórias com um volume corrente de 6 ml/kg e níveis de pressão expiratória final positiva de 5, 10, 15 e 20 cmH2O. Medimos as densidades do parênquima pulmonar em unidades Hounsfield e calculamos o recrutamento, recrutamento e desrecrutamento cíclico induzidos pela pressão expiratória final positiva, assim como o estiramento. RESULTADOS: O aumento dos níveis de pressão expiratória final positiva aumenta de forma consistente o recrutamento e o estiramento globais (p<0,01), o que se correlacionou de forma significante com a pressão de platô (r²=0,97; p<0,01). O aumento dos níveis de pressão expiratória final positiva aumentou sistematicamente a distensão alveolar em todo o eixo esternovertebral. CONCLUSÃO: A distensão alveolar é um efeito adverso da pressão expiratória final positiva que deve ser ponderado em qualquer paciente em relação ao seus potenciais benefícios no recrutamento. Em razão do número reduzido de pacientes, estes dados devem ser considerados como geradores de hipótese e não limitar a aplicação de valores elevados de pressão expiratória final positiva em pacientes com hipoxemia grave.

OBJECTIVE: The objective of this study was to assess the effects of positive end-expiratory pressure on recruitment, cyclic recruitment and derecruitment and strain in patients with acute lung injury and acute respiratory distress syndrome using lung computed tomography. METHODS: This is an open, controlled, non-randomized interventional study of ten patients with acute lung injury and acute respiratory distress syndrome. Using computed tomography, single, basal slices of the lung were obtained during inspiratory and expiratory pauses at a tidal volume of 6 ml/kg and a positive end-expiratory pressure of 5, 10, 15 and 20 cmH2O. The densities of the lung parenchyma were measured in Hounsfield units. The values for positive end-expiratory pressure-induced recruitment, cyclic recruitment and derecruitment and strain were then calculated. RESULTS: Increasing levels of positive end-expiratory pressure were correlated with increased recruitment and global strain (p < 0.01), which was significantly correlated with plateau pressure (r² = 0.97, p < 0.01). In addition, increasing levels of positive end-expiratory pressure systematically increased strain along the sternovertebral axis. CONCLUSION: While strain is an adverse effect of positive end-expiratory pressure, the decision use positive end-expiratory pressure with any patient should be balanced against the potential benefits of recruitment. Due to the small number of patients in this study, the present data should be treated as hypothesis generating and is not intended to limit the clinical application of a high level of positive end-expiratory pressure in patients with severe hypoxemia.

Biodisponibilidad del fósforo de cereales en aves / Cereal Phosphorus Bio-Availability in Chicks

En aves en crecimiento, se determinó la biodisponibilidad del fósforo del trigo, maíz y sorgo, mediante el método de relación de las pendientes de dietas referenciales con niveles crecientes de fósforo inorgánico y las de los cereales. Se utilizó como variable independiente el consumo de fósforo, para las dietas de referencia, y consumo de alimento, para las dietas con trigo, maíz o sorgo, y como variable dependiente el contenido de cenizas de la tibia de pollos de cuatro semanas de edad. El peso (g) y el contenido de cenizas (%) del hueso fueron superiores (P < 0,05) para el trigo (1020; 43,6), intermedios para el maìz (823; 30,44) y más bajos para el sorgo (655; 28,97). La ganancia de peso y contenido de cenizas se incrementó (P < 0,05) por cada aumento del nivel de fósforo inorgánico (0,25; 0,35; 0,45%) de las dietas de referencia. Las regresiones y correlaciones entre las variables de consumo y contenido de cenizas del hueso fueron significativas (P < 0,05) para los cereales y dietas referenciales. La relación entre las pendientes de las regresiones permitió estimar la biodisponibildad del fósforo del trigo, maíz y sorgo en 26,66; 24,67 y 23,0%, respectivamente.

In growing chicks, phosphorus bioavailability of wheat, corn and sorghum grains was determined by the slope relation between the regression equations of reference diets, with increasing levels of inorganic phosphorus, and those of the cereals. Phosphorus intake was used as independent variable, for references diets, and feed intake, for wheat, corn or sorghum diets, and tibia bone ash of 4 week old chicks as dependent variable. Weight (g) and bone ash (%) content were higher (P < 0.05) for wheat (1020; 43.6), intermediate for corn (823; 30.44) and lower for sorghum (655; 28.97). Body weight (g) gain and bone ash (%) were greater (P < 0.05) for each increasing levels of inorganic phosphorus (0.25, 0.35, 0.45%) of the reference diets. Regressions and correlations between phosphorus intake and bone ash were significant (P < 0.05) for cereal and reference diets. According the slope relation of the regression equations, phosphorus bioavailability values of wheat, corn and sorghum were 26.66, 24.67 and 23.0% respectively.

Desarrollo de un modelo experimental de hipertensión intra-abdominal / Development of an experimental model of intra-abdominal hypertension

Objetivos: Desarrollar un modelo porcino experimental de hipertensión intra-abdominal. Estudiar los efectos de la hipertensión intra-abdominal sobre la macro-hemodinamia, parámetros ventilatorios y perfusión esplácnica. Métodos: Se sometió a anestesia y ventilación mecánica a un grupo de 5 cerdos machos. Se realizó monitorización hemodinámica invasiva. Se sometió a los animales a una laparotomía para cateterizar la vena porta e instalar un tonómetro intrayeyunal, y se elevó la presión intra-abdominal a 15 mmHg infundiendo manitol 7,5 por ciento a la cavidad abdominal. Una hora después se volvieron a realizar mediciones y posteriormente se realizaron incrementos sucesivos de la presión intra-abdominal a niveles de 25 y 35 mmHg. Resultados: La hipertensión intra-abdominal produjo una disminución del gasto cardíaco (p <0,001) con aumento de la presión venosa central (p <0,001) y la presión de oclusión en la arteria pulmonar (p=0,073). Existió un incremento significativo en las presiones pico y meseta de la vía aérea, asociado a una reducción de la distensibilidad toraco-pulmonar (p <0,001). De los parámetros de perfusión regional el pH intramucoso fue el más precoz y sensible en detectar hipoperfusión esplácnica(p=0,04). El lactato arterial y venoso portal no tuvieron una buena correlación con el aumento de la presión intra-abdominal(p=NS). Conclusiones: El modelo presenta cambios hemodinámicos, ventilatorios y de perfusión esplácnica reproducibles que son concordantes con los observados en el SCA y constituye un instrumento valioso para futuros estudios de intervención terapéutica.

Peep intrínseco (PEEPi) en dos estrategias ventilatorias: volumen corriente tradicional versus volumen corriente bajo y frecuencia respiratoria alta / Intrinsic Peep (PEEPi)in two ventilator strategies: traditional tidal volume versus low tidal volume and high respiratory frequency

La ventilación con volumen corriente (Vt) de 6 ml/kg disminuyó en más de 20 por ciento la mortalidad del SDRA versus el uso de Vt de 12 ml/kg (ARDSnetwork). el uso de frecuencias respiratorias cercanas a 30 por minuto, en el grupo con Vt pequeño, pudiera generar la presencia de autoPEEP o PEEP intrínseco (PEEPi). Quisimos evaluar el nivel de PEEPi en pacientes con SDRA en su fase aguda en las dos condiciones de ventilación del estudio del ARDSnetwork.Estudiamos ocho pacientes con un SDRA en su fase precoz, que fueron ventilados en las dos modalidades en forma secuencial: a) estrategia protectora, Vt 6,2 ml/kg; FR 29; PEEP externo 9,4 cmH2O; b) estrategia convencional, Vt 11,8 ml/kg; FR 16; PEEP externo 8,6 cmH2O. Después de 15 minutos, el PEEP total se midió mediante una pausa espiatoria de 5 segundos. Se definió el PEEPi como el PEEP total menos el PEEP externo.

Valor pronóstico de la proteína C reactiva en pacientes sometidos a ventilación mecánica / Predictive value of C-reactive protein in patients receiving mechanical ventilation

La Proteína C Reactiva (PCR) es una de las proteínas de fase aguda más utilizadas en clínica, como marcador de infección y de intensidad de la respuesta inflamatoria. En el presente estudio evaluamos la utilidad clínica de la PCR en pacientes críticos sometidos a ventilación mecánica (VM). De 214 pacientes admitidos a la UCI Quirúrgica desde junio de 1999 a diciembre del 2000 y que fueron ventilados por más de 24 horas, 160 (75 por ciento) tenían medición de PCR. El 73 por ciento de ellos ingresó por problemas infecciosos, mientras el 27 por ciento lo hizo por problemas neurológicos. No hubo diferencia entre la PCR de ingreso o PCR máxima de los pacientes que sobrevivieron y los que fallecieron. Tampoco hubo correlación entre el valor de la PCR y los días de UCI, días de VM y días libres de VM. La mortalidad de 131 pacientes que alcanzaron la PCR máxima antes de las primeras 72 horas de admisión a la UCI fue inferior a aquellos que la presentaron después de las 72 horas (17,6 por ciento vs 44,8 por ciento, p<0,05). En el presente estudio, la PCR como valor aislado no mostró gran valor pronóstico en cuanto a la sobrevida de los pacientes, ni a los días en UCI o en VM. Sin embargo, su evolución en el tiempo aporta información clínica que puede ser relevante en el manejo de los pacientes ventilados.

El índice de oxigenación es un mejor indicador del intercambio gaseoso que la relación PaO2: FiO2 en pacientes adultos sometidos a ventilación mecánica / Oxygenation index is a better indicator of gaseous interchange than PaO2/FiO2 ratio in adult patients receiving mechanical ventilation

Oxygenation Index (Oxlx = MAP x 100 / Pa/FiO2) has been widely used to assess gas exchange in pediatric patients. We evaluated Oxlx and PaO2:FiO2 ratio (Pa/FiO2) in adults patients under Mechanical Ventilation (MV). Seventy-two patients (39 M, 33 F, 53 ± 21 yo, APACHE II 17 ± 7) required MV for 4 ± 3 days (1-18), of which 17 died (24 per cent). Arterial blood gases along FiO2, PEEP and mean airway pressure (MAP), to calculate Pa/FiO2 and Oxlx, and static toraco-pulmonar Compliance (Cst) were measured on a daily basis. Compliance had a good correlation with Oxlx (r = -0.7, p = 0.0001) and Pa/FiO2 (r = 0.5, p = 0.0001). Correlation between Cst and Oxlx improved (r = 0.8, p = 0.0001) when considering only Acute Respiratory Failure patients (ARF, n = 37). Mortality in ARF patients was related to a greater MAP, lower Cst and a worst Oxlx but not Pa/FiO2. Patients who fulfilled ARDS criteria had the worst Pa/FiO2, Oxlx and Cst values. In contrast, no relationship could be observed between Cst and gas exchange markers in neurologic patients (n = 22), or between these parameters and mortality. Oxygenation Index seems to be a better marker of gas exchange than Pa/FiO2 in adults patients under MV. It had a better relationship with the impairment in pulmonary function and mortality in ARF patients.