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.

Difficult ventilation in a patient with a giant aortic aneurysm: A challenge for the anesthesiologist.

Patients with Marfan syndrome present anatomic variations that may increase the risk of a difficult airway. Moreover, they can present large aortic aneurysms, which may cause extrinsic airway compression. Therefore, difficult ventilation during general anesthesia poses a challenge in that the anesthesiologist has to promptly make a crucial differential diagnosis. Multidisciplinary preoperative assessment and planning of the airway and ventilation management are of utmost importance in such uncommon and highly complex clinical cases. Fiberoptic bronchoscopy is probably a really useful tool in order to assess the severity and extent of the airway compression, both preoperatively and intraoperatively. We present a clinical case where difficult ventilation occurred immediately after the induction of general anesthesia.

Actionable Factors Fostering Health Value Generation and Scalability of Prehabilitation: A Prospective Cohort Study.

IMPORTANCE: Prehabilitation has potential for improving surgical outcomes as shown in previous randomized controlled trials. However, a marked efficacy-effectiveness gap is limiting its scalability. Comprehensive analyses of deployment of the intervention in real-life scenarios are required. OBJECTIVE: To assess health outcomes and cost of prehabilitation. DESIGN: Prospective cohort study with a control group built using propensity score-matching techniques. SETTING: Prehabilitation Unit in a tertiary-care university hospital. PARTICIPANTS: Candidates for major digestive, cardiac, thoracic, gynecologic, or urologic surgeries. INTERVENTION: Prehabilitation program, including supervised exercise training, promotion of physical activity, nutritional optimization, and psychological support. MAIN OUTCOMES AND MEASURES: The comprehensive complication index, hospital and intensive care unit length of stay, and hospital costs per patient until 30 days after surgery. Patients were classified by the degree of program completion and level of surgical aggression for sensitivity analysis. RESULTS: The analysis of the entire study group did not show differences in study outcomes between prehabilitation and control groups (n=328 each). The per-protocol analysis, including only patients completing the program (n=112, 34%), showed a reduction in mean hospital stay [9.9 (7.2) vs 12.8 (12.4) days; P =0.035]. Completers undergoing highly aggressive surgeries (n=60) additionally showed reduction in mean intensive care unit stay [2.3 (2.7) vs 3.8 (4.2) days; P =0.021] and generated mean cost savings per patient of €3092 (32% cost reduction) ( P =0.007). Five priority areas for action to enhance service efficiencies were identified. CONCLUSIONS AND RELEVANCE: The study indicates a low rate of completion of the intervention and identifies priority areas for re-design of service delivery to enhance the effectiveness of prehabilitation.

Repeatability and learning effect in the 6MWT in preoperative cancer patients undergoing a prehabilitation program.

OBJECTIVE: The main objective was to assess repeatability and learning effect of the 6-min walk test (6MWT) in a cohort of preoperative cancer patients referred to a prehabilitation program. As a secondary objective, we aimed to identify determinants of improvement in the second test. MATERIALS AND METHODS: Secondary analysis from a large prospective study on the implementation of a multimodal prehabilitation program in a real-life scenario. Eligible patients were assessed at baseline before starting the prehabilitation program. The 6MWT was conducted according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with two tests being performed under identical conditions separated by 30 min. The distance covered (in meters) and the physiological responses (heart rate, oxygen saturation, fatigue, and dyspnea) to each test were recorded and compared. RESULTS: A total of 170 patients (60.9%) were analyzed. Repeatability of the distance covered with the 6MWT was excellent (ICC = 0.98; 95% CI: 0.92-0.99), but a mean increase of + 19.5 m (95% CI: 15.6-23.5 m; p = < .001) in the second test was found, showing a learning effect with limits of agreement between - 31.3 and 70.4 m. Coefficient of variation was 4%. No clinical factor was found to be associated with an improvement in the second test. CONCLUSIONS: The 6MWT showed excellent repeatability in preoperative cancer patients, but a significant learning effect is present. No associated factors with a clinically meaningful improvement in the second test were identified. In light of these findings, two attempts of the 6MWT should be encouraged in this population.

Multimodal prehabilitation as strategy for reduction of postoperative complications after cardiac surgery: a randomised controlled trial protocol.

INTRODUCTION: Prehabilitation programmes that combine exercise training, nutritional support and emotional reinforcement (multimodal prehabilitation) have demonstrated efficacy reducing postoperative complications in the context of abdominal surgery. However, such programmes have seldom been studied in cardiac surgery, one of the surgeries associated with higher postoperative morbidity and mortality. This trial will assess the feasibility and efficacy in terms of reduction of postoperative complications and cost-effectiveness of a multimodal prehabilitation programme comparing to the standard of care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre, randomised, open-label, controlled trial with a 1:1 ratio. Consecutive 160 elective valve replacement and/or coronary revascularisation surgical patients will be randomised to either standard of care or 4-6 weeks of multimodal prehabilitation that will consist in (1) two times/week supervised endurance and strength exercise training sessions, (2) promotion of physical activity and healthy lifestyle, (3) respiratory physiotherapy, (4) nutrition counselling and supplementation if needed, and (5) weekly mindfulness sessions. Baseline, preoperative and 3-month postoperative data will be collected by an independent blinded evaluator. The primary outcome of this study will be the incidence of postoperative complications. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of Clinical investigation of Hospital Clinic de Barcelona (HCB/2017/0708). The results will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03466606.

Cost-effectiveness of a technology-supported multimodal prehabilitation program in moderate-to-high risk patients undergoing lung cancer resection: randomized controlled trial protocol.

BACKGROUND: Multimodal prehabilitation is a preoperative intervention with the objective to enhance cancer patients' functional status which has been showed to reduce both postoperative morbidity and hospital length of stay in digestive oncologic surgery. However, in lung cancer surgery patients further studies with higher methodological quality are needed to clarify the benefits of prehabilitation. The main aim of the current protocol is to evaluate the cost-effectiveness of a multimodal prehabilitation program supported by information and communication technologies in moderate-to-high risk lung cancer patients undergoing thoracic surgery. METHODS: A Quadruple Aim approach will be adopted, assessing the prehabilitation program at the following levels: i) Patients' and professionals' experience outcomes (by means of standardized questionnaires, focus groups and structured interviews); ii) Population health-based outcomes (e.g. hospital length of stay, number and severity of postoperative complications, peak oxygen uptake and levels of systemic inflammation); and, iii) Healthcare costs. DISCUSSION: This study protocol should contribute not only to increase the scientific basis on prehabilitation but also to detect the main factors modulating service adoption. TRIAL REGISTRATION: NCT04052100 (August 9, 2019).

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.

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.