Mechanism-Based Modeling of Perioperative Variations in Hemoglobin Concentration in Patients Undergoing Laparoscopic Surgery.

BACKGROUND: Hemoglobin concentration ([Hb]) in the perioperative setting should be interpreted in the context of the variables and processes that may affect it to differentiate the dilution effects caused by changes in intravascular volume. However, it is unclear what variables and processes affect [Hb]. Here, we modeled the perioperative variations in [Hb] to identify the variables and processes that govern [Hb] and to describe their effects. METHODS: We first constructed a mechanistic framework based on the main variables and processes related to the perioperative [Hb] variations. We then prospectively studied patients undergoing laparoscopic surgery, divided into 2 consecutive cohorts for the development and validation of the model. The study protocol consisted of serial measurements of [Hb] along with recordings of hemoglobin mass loss, blood volume loss, fluid infusion, urine volume, and inflammatory biomarkers measurements, up to 96 hours postoperatively. Mathematical fitting was performed using nonlinear mixed-effects. Additionally, we performed simulations to explore the effects of blood loss and fluid therapy protocols on [Hb]. RESULTS: We studied 154 patients: 118 enrolled in the development group and 36 in the validation group. We characterized the perioperative course of [Hb] using a mass balance model that accounted for hemoglobin losses during surgery, and a 2-compartment model that estimated fluid kinetics and intravascular volume changes. During model development, we found that urinary fluid elimination represented only 24% of the total fluid elimination, and that total fluid elimination was inhibited after surgery in a time-dependent manner and influenced by age. Also, covariate evaluation showed a significant association between the type of surgery and proportion of fluid eliminated via urine. In contrast, neither the type of infused solution, blood volume loss nor inflammatory biomarkers were found to correlate with model parameters. In the validation analysis, the model demonstrated a considerable predictive capacity, with 95% of the predicted [Hb] within -4.4 and +5.5 g/L. Simulations demonstrated that hemoglobin mass loss determined most of the postoperative changes in [Hb], while intravascular volume changes due to fluid infusion, distribution, and elimination induced smaller but clinically relevant variations. Simulated patients receiving standard fluid therapy protocols exhibited a hemodilution effect that resulted in a [Hb] decrease between 7 and 15 g/L at the end of surgery, and which was responsible for the lowest [Hb] value during the perioperative period. CONCLUSIONS: Our model provides a mechanistic and quantitative understanding of the causes underlying the perioperative [Hb] variations.

Agreement of surgical blood loss estimation methods.

BACKGROUND: Surgical blood loss is usually estimated by different formulae in studies of strategies aimed at reducing perioperative bleeding. This study assessed and compared the agreement of the main blood loss estimation formulae using a direct measurement of blood loss as the reference method. STUDY DESIGN AND METHODS: Eighty consecutive patients undergoing urologic laparoscopic surgery were studied. Only optimal conditions for the direct measurement of surgical blood loss were considered. Surgical blood loss was estimated by six formulae at four different postoperative time points. The agreement of the formulae was evaluated by the Concordance correlation coefficient (CCC) and Bland-Altman analyses. An analysis of the agreement's variability regarding different magnitudes of blood loss was also performed. RESULTS: Directly measured blood loss ranged from 200 to 2200 mL. The formulae studied showed poor agreement with the direct measurement of blood loss; 95% limits of agreement widely exceeded the criterion of ±560 mL. Significant biases were found, which for most of the formulae led to an overestimation of blood loss. For all formulae, agreement remained constant regardless of the amount of blood loss, with limits between -40 and +120% approximately. Among the formulae, the best agreement was achieved by López-Picado's formula at 48 hours (CCC: 0.577), with a bias of +283 mL and 95% limits of agreement between -477 and +1043 mL. CONCLUSION: Formulae currently used to estimate surgical blood loss differ substantially from direct measurements; therefore, they may not be reliable methods of blood loss quantification in the surgical setting.

Semimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids.

Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.

Perioperative blood loss: estimation of blood volume loss or haemoglobin mass loss?

BACKGROUND: Perioperative blood loss is an essential parameter in research into Patient Blood Management. However, currently there is no "gold standard" method to quantify it. Direct measurements of blood loss are considered unreliable methods, and the formulae to estimate it have proven to be significantly inaccurate. Given the need for better research tools, this study evaluated an estimation of haemoglobin mass loss as an alternative approach to estimate perioperative blood loss, and compared it to estimations based on blood volume loss. MATERIAL AND METHODS: We studied one hundred consecutive patients undergoing urological laparoscopic surgery. Both haemoglobin mass loss and blood volume loss were directly measured during surgery, under highly controlled conditions for a reliable direct measurement of blood loss. Three formulae were studied: 1) a haemoglobin mass loss formula, which estimated blood loss in terms of haemoglobin mass loss, 2) the López-Picado's formula and 3) an empirical volume formula that estimated blood loss in terms of blood volume loss. The empirical volume formula was developed within the study with the aim of providing the best possible estimation of blood volume loss in the studied population. The formulae were evaluated and compared by assessing their agreements with their respective direct measurements of blood loss. RESULTS: The haemoglobin mass loss formula met the predefined agreement criterion of ±71 g, with 95% limits of agreement ranging from 0.6 to 44.1 g and a moderate overestimation of 22.4. In comparison to both blood volume loss formulae, the haemoglobin mass loss formula was superior in every agreement parameter evaluated. DISCUSSION: In this study, the estimation of haemoglobin mass loss was found to be a more accurate method to estimate perioperative blood loss. This estimation method could be a robust research tool, although more studies are needed to establish its reliability.

Trauma cerrado de aorta torácica, desde el servicio de urgencias hasta el quirófano: revisión narrativa / Blunt trauma of the thoracic aorta, from the emergency department to the operating room: narrative review / Trauma contuso da aorta torácica: do pronto-socorro ao centro cirúrgico, uma revisão narrativa

El trauma es la principal causa de muerte de la población en edad productiva. El abordaje del trauma torácico cerrado todavía es un desafío para el médico de urgencias. Aunque no es una entidad frecuente, se asocia con una alta mortalidad y resultados adversos. El diagnóstico del trauma cerrado de aorta torácica (LCAT) requiere un alto índice de sospecha, dado que los signos y síntomas no son específicos de esta enfermedad (dolor torácico, dolor interescapular, disnea, disfagia, estridor, disfonía). Es importante resaltar que la ausencia de inestabilidad hemodinámica no debe descartar una lesión aórtica. Para su diagnóstico imagenológico se debe tener en cuenta que los rayos X de tórax no tienen el rendimiento adecuado, el patrón de referencia es la angiotomografía y el ecocardiograma transesofágico (ETE) constituye una opción diagnóstica. El manejo incluye líquidos endovenosos y antihipertensivos como medida transitoria, manejo quirúrgico definitivo y, en algunos casos, manejo expectante o diferido. Los pacientes inestables o con signos de ruptura inminente deben ser llevados de manera inmediata a cirugía. El manejo quirúrgico temprano ha impactado en la mortalidad. A pesar de los avances en las técnicas quirúrgicas, la técnica quirúrgica abierta documenta mayor tasa de mortalidad que el manejo endovascular, el cual tiene numerosas ventajas al ser poco invasivo. Esta es una revisión narrativa que destaca algunos aspectos clave sobre los mecanismos de lesión, diagnóstico y manejo inicial del trauma cerrado aorta torácica. Por último, se propone un algoritmo de abordaje de trauma de aorta.

Trauma is the leading cause of death in the productive-age population. Addressing blunt chest trauma is still a challenge for the emergency physician. Although it is not a common entity, it is associated with high mortality and adverse outcomes. The diagnosis of blunt thoracic aortic trauma (LCAT) requires a high index of suspicion, given that the signs and symptoms are not specific to this disease (chest pain, interscapular pain, dyspnea, dysphagia, stridor, dysphonia). It is important to highlight that the absence of hemodynamic instability should not rule out aortic injury. For its imaging diagnosis, it must be taken into account that chest X-rays do not have adequate performance; the reference standard is angiotomography and transesophageal echocardiography (TEE) is a diagnostic option. Management includes intravenous fluids and antihypertensives as a temporary measure, definitive surgical management and, in some cases, expectant or deferred management. Unstable patients or patients with signs of imminent ruptura should be taken immediately to surgery. Early surgical management has impacted mortality. Despite advances in surgical techniques, the open surgical technique documents a higher mortality rate than endovascular management, which has numerous advantages as it is minimally invasive. This is a narrative review that highlights some key aspects about the mechanisms of injury, diagnosis and initial management of blunt thoracic aortic trauma. Finally, an algorithm for addressing aortic trauma is proposed.

O trauma é a principal causa de morte na população em idade produtiva. Abordar o trauma torácico contuso ainda é um desafio para o médico emergencista. Embora não seja uma entidade comum, está associada a alta mortalidade e resultados adversos. O diagnóstico de trauma fechado de aorta torácica (TACE) requer alto índice de suspeição, visto que os sinais e sintomas não são específicos desta doença (dor torácica, dor interescapular, dispneia, disfagia, estridor, disfonia). É importante ressaltar que a ausência de instabilidade hemodinâmica não deve descartar lesão aórtica. Para seu diagnóstico por imagem deve-se levar em consideração que a radiografia de tórax não apresenta desempenho adequado; o padrão de referência é a angiotomografia e a ecocardiografia transesofágica (ETE) é uma opção diagnóstica. O manejo inclui fluidos intravenosos e anti-hipertensivos como medida temporária, manejo cirúrgico definitivo e, em alguns casos, manejo expectante ou diferido. Pacientes instáveis ou com sinais de ruptura iminente devem ser encaminhados imediatamente para cirurgia. O manejo cirúrgico precoce impactou a mortalidade. Apesar dos avanços nas técnicas cirúrgicas, a técnica cirúrgica aberta documenta maior taxa de mortalidade do que o manejo endovascular, que apresenta inúmeras vantagens por ser minimamente invasivo. Esta é uma revisão narrativa que destaca alguns aspectos-chave sobre os mecanismos de lesão, diagnóstico e manejo inicial do trauma contuso da aorta torácica. Finalmente, é proposto um algoritmo para tratar o trauma aórtico.