The use of Guyton's approach to the control of cardiac output for clinical fluid management.

Infusion of fluids is one of the most common medical acts when resuscitating critically ill patients. However, fluids most often are given without consideration of how fluid infusion can actually improve tissue perfusion. Arthur Guyton's analysis of the circulation was based on how cardiac output is determined by the interaction of the factors determining the return of blood to the heart, i.e. venous return, and the factors that determine the output from the heart, i.e. pump function. His theoretical approach can be used to understand what fluids can and cannot do. In his graphical analysis, right atrial pressure (RAP) is at the center of this interaction and thus indicates the status of these two functions. Accordingly, trends in RAP and cardiac output (or a surrogate of cardiac output) can provide important guides for the cause of a hemodynamic deterioration, the potential role of fluids, the limits of their use, and when the fluid is given, the response to therapeutic interventions. Use of the trends in these values provide a physiologically grounded approach to clinical fluid management.

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

The Ins and Outs of IV Fluids in Hemodynamic Resuscitation.

OBJECTIVES: Concise definitive review of the physiology of IV fluid (IVF) use in critically ill patients. DATA SOURCES: Available literature on PubMed and MEDLINE databases. STUDY SELECTION: Basic physiology studies, observational studies, clinical trials, and reviews addressing the physiology of IVF and their use in the critically ill were included. DATA EXTRACTION: None. DATA SYNTHESIS: We combine clinical and physiologic studies to form a framework for understanding rational and science-based use of fluids and electrolytes. CONCLUSIONS: IVF administration is among the most common interventions for critically ill patients. IVF can be classified as crystalloids or colloids, and most crystalloids are sodium salts. They are frequently used to improve hemodynamics during shock states. Many recent clinical trials have sought to understand which kind of IVF might lead to better patient outcomes, especially in sepsis. Rational use of IVF rests on understanding the physiology of the shock state and what to expect IVF will act in those settings. Many questions remain unanswered, and future research should include a physiologic understanding of IVF in study design.

Fontan Heart: Insight Into the Physiological Role of the Right Heart.

BACKGROUND: Cardiac output (CO) is almost normal in children born without a functional right ventricle (RV), and a Fontan repair, so why is RV dysfunction such a clinical problem? We tested the hypotheses that increased pulmonary vascular resistance (PVR) is the dominant factor and volume expansion by any means is of limited benefit. METHODS: We removed the RV from a previously used MATLAB model and altered vascular volume, venous compliance (Cv), PVR, and measures of left ventricular (LV) systolic and diastolic function. CO and regional vascular pressures were the primary outcome measures. RESULTS: RV removal decreased CO by 25%, and raised mean systemic filling pressure (MSFP). A 10 mL/kg increase in stressed volume only moderately increased CO with or without the RV. Decreasing systemic Cv increased CO but also markedly increased pulmonary venous pressure. With no RV, increasing PVR had the greatest effect on CO. Increasing LV function had little benefit. CONCLUSIONS: Model data indicate that increasing PVR dominates the decrease in CO in Fontan physiology. Increasing stressed volume by any means only moderately increased CO and increasing LV function had little effect. Decreasing systemic Cv unexpectedly markedly increased pulmonary venous pressures even with the RV intact.

Interchangeability of transthoracic and transesophageal echocardiographic right heart measurements in the perioperative setting and correlation with hemodynamic parameters.

Reduction of right ventricular (RV) function after cardiac surgery has been shown to impact outcomes. Conventional indices for right ventricular dysfunction are validated using transthoracic echocardiogram (TTE) which has limited use compared to transesophageal echocardiogram (TEE) in the perioperative settings. The aim of this study was to assess the agreement of RV systolic function assessment with TEE compared to TTE and assess the association of echocardiographic parameter with hemodynamic indices of RV dysfunction. This was a single center prospective observational study in an academic institution. Fifty adult patients undergoing elective cardiac surgery were included. TTE, TEE and stroke volume measurements pre-cardiopulmonary bypass (CPB) and post-CPB were performed. The variables of interest were anatomical M-mode tricuspid annular plane systolic excursion (AMM-TAPSE), fractional area change (FAC), tricuspid annular velocity (S') and myocardial performance index (MPI). FAC and AMM-TAPSE measured at the mid-esophageal 4 chamber view had substantial agreement with the TTE acquired parameters (Lin's concordance correlation coefficient (CCC) = 0.76, 95%CI 0.59-0.86 and CCC = 0.85, 95%CI 0.76-0.91). S' was significantly underestimated by TEE (CCC = 0.07, 95%CI 0.04-0.19) and MPI showed moderate agreement (CCC = 0.45 95%CI 0.19-0.65). Despite the significant changes in echocardiographic parameters, there were no corresponding changes in stroke volume (SV) or pulmonary artery pulsatility index at the post-CPB period. TEE acquired FAC and AMM-TAPSE had substantial agreement with pre-operative TTE values and no significant differences between the pre-CPB and post-CPB period. Systolic RV echocardiographic parameters decreased post-CPB but this was not accompanied by significant hemodynamic changes.

Right Ventricular Limitation: A Tale of Two Elastances.

Right ventricular (RV) dysfunction is a commonly considered cause of low cardiac output in critically ill patients. Its management can be difficult and requires an understanding of how the RV limits cardiac output. We explain that RV stroke output is caught between the passive elastance of the RV walls during diastolic filling and the active elastance produced by the RV in systole. These two elastances limit RV filling and stroke volume and consequently limit left ventricular stroke volume. We emphasize the use of the term "RV limitation" and argue that limitation of RV filling is the primary pathophysiological process by which the RV causes hemodynamic instability. Importantly, RV limitation can be present even when RV function is normal. We use the term "RV dysfunction" to indicate that RV end-systolic elastance is depressed or diastolic elastance is increased. When RV dysfunction is present, RV limitation occurs at lowerpulmonary valve opening pressures and lower stroke volume, but stroke volume and cardiac output still can be maintained until RV filling is limited. We use the term "RV failure" to indicate the condition in which RV output is insufficient for tissue needs. We discuss the physiological underpinnings of these terms and implications for clinical management.

Right Ventricular Loading by Lung Inflation during Controlled Mechanical Ventilation.

Rationale: The inspiratory rise in transpulmonary pressure during mechanical ventilation increases right ventricular (RV) afterload. One mechanism is that when Palv exceeds left atrial pressure, West zone 1 or 2 (non-zone 3) conditions develop, and Palv becomes the downstream pressure opposing RV ejection. The Vt at which this impact on the right ventricle becomes hemodynamically evident is not well established. Objectives: To determine the magnitude of RV afterload and prevalence of significant non-zone 3 conditions during inspiration across the range of Vt currently prescribed in clinical practice. Methods: In postoperative passively ventilated cardiac surgery patients, we measured right atrial, right ventricle, pulmonary artery, pulmonary artery occlusion pressure, plateau pressure, and esophageal pressure during short periods of controlled ventilation, with Vt increments ranging between 2 and 12 ml/kg predicted body weight (PBW). The inspiratory increase in RV afterload was evaluated hemodynamically and echocardiographically. The prevalence of non-zone 3 conditions was determined using two definitions based on changes in esophageal pressure, pulmonary artery occlusion pressure, and plateau pressure. Measurements and Main Results: Fifty-one patients were studied. There was a linear relationship between Vt, driving pressure, transpulmonary pressure, and the inspiratory increase in the RV isovolumetric contraction pressure. Echocardiographically, increasing Vt was associated with a greater inspiratory increase in markers of afterload and a decrease in stroke volume. Non-zone 3 conditions were present in >50% of subjects at a Vt ⩾ 6 ml/kg PBW. Conclusions: In the Vt range currently prescribed, RV afterload increases with increasing Vt. A mechanical ventilation strategy that limits Vt and driving pressure is cardioprotective.

Intracellular pH regulation and the acid delusion.

The hydrogen ion concentration ([H+]) in intracellular cytoplasmic fluid (ICF) must be maintained in a narrow range in all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH notation, failure to consider the roles played by differences in the concentration of strong ions (strong ion difference, SID), the conservation of mass, the principle of electrical neutrality, and that [H+] and bicarbonate ions [HCO3-] are dependent variables. This argument is based on the late Peter Stewart's physical-chemical analysis of [H+] regulation reported in this journal nearly forty years ago (Stewart. 1983. Can. J. Physiol. Pharmacol. 61: 1444-1461. Doi:10.1139/y83-207). We start by outlining the principles of Stewart's analysis and then provide a general understanding of its significance for regulation of ICF [H+]. The system may initially appear complex, but it becomes evident that changes in SID dominate regulation of [H+]. The primary strong ions are Na+, K+, and Cl-, and a few organic strong anions. The second independent variable, partial pressure of carbon dioxide (PCO2), can easily be assessed. The third independent variable, the activity of intracellular weak acids ([Atot]), is much more complex but largely plays a modifying role. Attention to these principles will potentially provide new insights into ICF pH regulation.

Incidencia del síndrome de Burnout en residentes de terapia intensiva en hospitales de tercer nivel estudio multicéntrico internacional (estudio INCIBUS) / Incidence of Burnout syndrome in intensive care residents in third-level hospitals. International multicentre study (INCIBUS study) / Incidência da síndrome de Burnout em residentes de terapia intensiva em hospitais de terceiro nível estudo multicêntrico internacional (estudo INCIBUS)

Resumen: Introducción: El síndrome de Burnout es una entidad que surge de una respuesta continua a condiciones de estrés crónico en ambientes de alta demanda de atención. La literatura internacional reporta la presentación de este síndrome entre residentes de 27 a 75%, dependiendo de la especialidad. Objetivo: Conocer la incidencia del síndrome en residentes de terapia intensiva en hospitales de tercer nivel de atención en Norteamérica. Material y métodos: Estudio prospectivo, transversal, observacional. Población: Residentes de Terapia Intensiva, en hospitales de tercer nivel (México y Canadá). Se empleó cuestionario Maslach, análisis SPSS 25, estadística descriptiva para distribución de variables, comparación entre grupos U de Mann-Whitney, comparación entre grupos prueba exacta de Fisher, p < 0.05. Resultados: El síndrome de Burnout está presente en 100% de los residentes de cuidados críticos estudiados. Conclusión: El síndrome de Burnout tiene una alta incidencia en residentes de cuidados críticos de hospitales de tercer nivel en Norteamérica. Se requiere mayor número de estudios, evaluar diferencias en programas de residencias para tener más información de la presentación de este síndrome en una de las especialidades que demandan el más alto nivel de atención y cuidado en los pacientes.

Abstract: Introduction: Burnout syndrome is an entity that arises from a continuous response to conditions of chronic stress in environments with high demand for attention. International literature reports presentation of this syndrome among residents from 27 to 75%, depending on the specialty. Objective: To know incidence of syndrome in residents of intensive care in hospitals of third level of care in North America. Material and methods: Prospective, cross-sectional, observational study. Population: Intensive therapy residents, in third level hospitals (Mexico and Canada). Maslach questionnaire was used, SPSS 25 analysis, descriptive statistics for distribution of variables, comparison between Whitney U Mann groups, comparison between Fisher's exact test groups, p < 0.05. Results: Burnout syndrome is present in 100% of the critical care residents studied. Conclusion: Burnout syndrome has a high incidence in critical care residents of tertiary hospitals in North America. More studies are required, evaluate differences in residency programs to have more information about the presentation of this syndrome in one of the specialties that demand highest level of attention and care in patients.

Resumo: Introdução: A síndrome de Burnout é uma entidade que surge de uma resposta contínua a condições de estresse crônico em ambientes de alta demanda de atenção. A literatura internacional relata a apresentação dessa síndrome entre os residentes de 27 a 75%, dependendo da especialidade. Objetivo: Conhecer a incidência da síndrome em residentes de terapia intensiva em hospitais de terceiro nível na América do Norte. Material e métodos: Estudo prospectivo, transversal, observacional. População: Residentes de terapia intensiva, em hospitais de terceiro nível (México e Canadá). Utilizou-se o questionário Maslach, análise SPSS 25, estatística descritiva para distribuição das variáveis, comparação entre os grupos Whitney U Mann, comparação entre os grupos de teste exato de Fisher, p < 0.05. Resultados: A síndrome de Burnout está presente em 100% dos residentes de terapia intensiva estudados. Conclusão: A síndrome de Burnout tem alta incidência em residentes de terapia intensiva de hospitais de terceiro nível na América do Norte. Requeremos mais estudos para avaliar as diferenças nos programas de residência para obter mais informações sobre a apresentação dessa síndrome em uma das especialidades que demandam o mais alto nível de atendimento e atendimento em pacientes.

Periodicity, time constants of drainage, and the mechanical determinants of peak cardiac output during exercise.

To analyze mechanical adaptations that must occur in the cardiovascular system to reach the high cardiac outputs known to occur at peak aerobic performance, we adapted a computational model of the circulation by adding a second parallel venous compartment as proposed by August Krogh in 1912. One venous compartment has a large compliance and slow time constant of emptying; it is representative of the splanchnic circulation. The other has a low compliance and fast time constant of emptying and is representative of muscle beds. Fractional distribution between the two compartments is an important determinant of cardiac output. Parameters in the model were based on values from animal and human studies normalized to a 70 kg male. The baseline cardiac output was set at 5 L/min, and we aimed for 25 L/min at peak exercise with a fractional flow to the peripheral-muscle region of 90%. Finally, we added the equivalent of a muscle pump. Adjustments in circuit and cardiac parameters alone increased cardiac output to only 15.6 L/min because volume accumulated in the muscle compartment and limited a higher cardiac output. Addition of muscle contractions decompressed the muscle region and allowed cardiac output to increase to 23.4 L/min. The pulsatility of blood flow imposes important constraints on the adaptations of cardiac and circulatory functions because it fixes the times for filling and emptying. Flow is further limited by the limits of cardiac filling on each beat. Muscle contractions play a key role by decompressing volume that would otherwise accumulate in the muscle vasculature and by decreasing the time for stroke return to the right ventricle.NEW & NOTEWORTHY We used a computational model of the circulation and previous human and animal data to model mechanical changes in the heart and circulation that are needed to reach the known high cardiac output at peak aerobic exercise. Key points are that time constants of drainage of circulatory compartments put limits on peak flow in a pulsatile system. Muscle contractions increase the rate of return to the heart and by doing so prevent accumulation of volume in the muscle compartment and greatly increase circulatory capacity.

Diastolic pressure should be used to guide management of patients in shock: PRO.

Based primarily on the rational that adequate diastolic pressure is needed to maintain sufficient coronary blood for myocardial needs, diastolic pressure has been proposed as a treatment target for patients in shock. To date, clinical evidence supporting this is limited to observational data. Key points are that what is important for tissues is flow not pressure; the coronary circulation has very large flow reserves and can maintain flow with a low pressure; raising arterial pressure by only increasing vascular resistance does not alter tissue perfusion and could even increase myocardial oxygen demand. Targeting diastolic pressure can lead to over use of vasopressors, which studies have associated with worse outcome. Pressor management in shock should include assessment of indicators of tissue perfusion and changes in flow if possible.

Heart-Lung interaction in spontaneous breathing subjects: the basics.

Heart-lung interactions occur primarily because of two components of lung inflation, changes in pleural pressure and changes in transpulmonary pressure. Of these, changes in pleural pressure dominate during spontaneous breathing. Because the heart is surrounded by pleural pressure, during inspiration the environment of the heart falls relative to the rest of the body. This alters inflow into the right heart and outflow from the left heart. Alterations in transpulmonary pressure can alter the outflow from the right heart and the inflow to the left heart. These interactions are modified by the cardiac and respiratory frequency, ventricular function and magnitude of the respiratory efforts.

Physical contact between human vascular endothelial and smooth muscle cells modulates cytosolic and nuclear calcium homeostasis.

The interaction between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs) plays an important role in the modulation of vascular tone. There is, however, no information on whether direct physical communication regulates the intracellular calcium levels of human VECs (hVECs) and (or) human VSMCs (hVSMCs). Thus, the objective of the study is to verify whether co-culture of hVECs and hVSMCs modulates cytosolic ([Ca2+]c) and nuclear calcium ([Ca2+]n) levels via physical contact and (or) factors released by both cell types. Quantitative 3D confocal microscopy for [Ca2+]c and [Ca2+]n measurement was performed in cultured hVECs or hVSMCs or in co-culture of hVECs-hVSMCs. Our results show that: (1) physical contact between hVECs-hVECs or hVSMCs-hVSMCs does not affect [Ca2+]c and [Ca2+]n in these 2 cell types; (2) physical contact between hVECs and hVSMCs induces a significant increase only of [Ca2+]n of hVECs without affecting the level of [Ca2+]c and [Ca2+]n of hVSMCs; and (3) preconditioned culture medium of hVECs or hVSMCs does not affect [Ca2+]c and [Ca2+]n of both types of cells. We concluded that physical contact between hVECs and hVSMCs only modulates [Ca2+]n in hVECs. The increase of [Ca2+]n in hVECs may modulate nuclear functions that are calcium dependent.