Venous Minus Arterial Carbon Dioxide Gradients in the Monitoring of Tissue Perfusion and Oxygenation: A Narrative Review.

According to Fick's principle, the total uptake of (or release of) a substance by tissues is the product of blood flow and the difference between the arterial and the venous concentration of the substance. Therefore, the mixed or central venous minus arterial CO2 content difference depends on cardiac output (CO). Assuming a linear relationship between CO2 content and partial pressure, central or mixed venous minus arterial PCO2 differences (Pcv-aCO2 and Pmv-aCO2) are directly related to CO. Nevertheless, this relationship is affected by alterations in the CO2Hb dissociation curve induced by metabolic acidosis, hemodilution, the Haldane effect, and changes in CO2 production (VCO2). In addition, Pcv-aCO2 and Pmv-aCO2 are not interchangeable. Despite these confounders, CO is a main determinant of Pcv-aCO2. Since in a study performed in septic shock patients, Pmv-aCO2 was correlated with changes in sublingual microcirculation but not with those in CO, it has been proposed as a monitor for microcirculation. The respiratory quotient (RQ)-RQ = VCO2/O2 consumption-sharply increases in anaerobic situations induced by exercise or critical reductions in O2 transport. This results from anaerobic VCO2 secondary to bicarbonate buffering of anaerobically generated protons. The measurement of RQ requires expired gas analysis by a metabolic cart, which is not usually available. Thus, some studies have suggested that the ratio of Pcv-aCO2 to arterial minus central venous O2 content (Pcv-aCO2/Ca-cvO2) might be a surrogate for RQ and tissue oxygenation. In this review, we analyze the physiologic determinants of Pcv-aCO2 and Pcv-aCO2/Ca-cvO2 and their potential usefulness and limitations for the monitoring of critically ill patients. We discuss compelling evidence showing that they are misleading surrogates for tissue perfusion and oxygenation, mainly because they are systemic variables that fail to track regional changes. In addition, they are strongly dependent on changes in the CO2Hb dissociation curve, regardless of changes in systemic and microvascular perfusion and oxygenation.

Health inequities in the diagnosis and outcome of sepsis in Argentina: a prospective cohort study.

BACKGROUND: Socioeconomic variables impact health outcomes but have rarely been evaluated in critical illness. Low- and middle-income countries bear the highest burden of sepsis and also have significant health inequities. In Argentina, public hospitals serve the poorest segment of the population, while private institutions serve patients with health coverage. Our objective was to analyze differences in mortality between public and private hospitals, using Sepsis-3 definitions. METHODS: This is a multicenter, prospective cohort study including patients with sepsis admitted to 49 Argentine ICUs lasting 3 months, beginning on July 1, 2016. Epidemiological, clinical, and socioeconomic status variables and hospital characteristics were compared between patients admitted to both types of institutions. RESULTS: Of the 809 patients included, 367 (45%) and 442 (55%) were admitted to public and private hospitals, respectively. Those in public institutions were younger (56 ± 18 vs. 64 ± 18; p < 0.01), with more comorbidities (Charlson score 2 [0-4] vs. 1 [0-3]; p < 0.01), fewer education years (7 [7-12] vs. 12 [10-16]; p < 0.01), more frequently unemployed/informally employed (30% vs. 7%; p < 0.01), had similar previous self-rated health status (70 [50-90] vs. 70 [50-90] points; p = 0.30), longer pre-admission symptoms (48 [24-96] vs. 24 [12-48] h; p < 0.01), had been previously evaluated more frequently in any healthcare venue (28 vs. 20%; p < 0.01), and had higher APACHE II, SOFA, lactate levels, and mechanical ventilation utilization. ICU admission as septic shock was more frequent in patients admitted to public hospitals (47 vs. 35%; p < 0.01), as were infections caused by multiresistant microorganisms. Sepsis management in the ICU showed no differences. Twenty-eight-day mortality was higher in public hospitals (42% vs. 24%; p < 0.01) as was hospital mortality (47% vs. 30%; p < 0.01). Admission to a public hospital was an independent predictor of mortality together with comorbidities, lactate, SOFA, and mechanical ventilation; in an alternative prediction model, it acted as a correlate of pre-hospital symptom duration and infections caused by multiresistant microorganisms. CONCLUSIONS: Patients in public hospitals belonged to a socially disadvantaged group and were sicker at admission, had septic shock more frequently, and had higher mortality. Unawareness of disease severity and delays in the health system might be associated with late admission. This marked difference in outcome between patients served by public and private institutions constitutes a state of health inequity.

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial.

Importance: Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established. Objective: To determine if a peripheral perfusion-targeted resuscitation during early septic shock in adults is more effective than a lactate level-targeted resuscitation for reducing mortality. Design, Setting, and Participants: Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018. Interventions: Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period. Main Outcomes and Measures: The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation-, renal replacement therapy-, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay. Results: Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, -8.5% [95% CI, -18.2% to 1.2%]). Peripheral perfusion-targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, -1.00 [95% CI, -1.97 to -0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed. Conclusions and Relevance: Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT03078712.

Sublingual microcirculatory alterations in cirrhotic patients.

OBJECTIVE: To assess sublingual microcirculation in cirrhotic patients and its relationship to spider angiomas, complications, and outcome. METHODS: Thirty-one cirrhotic patients were prospectively compared to 31 matched controls. Sublingual microcirculation was evaluated by videomicroscopy. We specifically looked for capillaries with increased RBCV, which was defined as a velocity higher than the percentile 100th of controls. RESULTS: Compared to controls, cirrhotic patients showed decreased total and PVD (14.4 ± 2.2 vs 16.0 ± 1.3 and 14.1 ± 2.3 vs 15.9 ± 1.6 mm/mm2 , respectively, P < .001 for both) and increased HFI (0.64 ± 0.39 vs 0.36 ± 0.21, P = .001). They also exhibited high RBCV in 2% of the microvessels (P < .0001). Patients with MELD score ≥10 had higher RBCV than patients with score <10 (1414 ± 290 vs 1206 ± 239 µm/s, P < .05). Patients with spider angiomas showed lower vascular densities. Microcirculation did not differ between survivors and nonsurvivors. CONCLUSIONS: Cirrhosis is associated with microcirculatory alterations that can be easily monitored in the sublingual mucosa. Alterations included decreased density and PPV and hyperdynamic microvessels. The most striking finding, however, was the microvascular heterogeneity. Patients with spider angiomas had more severe alterations. Larger studies should clarify the relationship between microcirculatory abnormalities and outcome.

Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.

OBJECTIVES: The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. DESIGN: Cohort study of 3-month duration beginning on July 1, 2016. SETTINGS: Forty-nine ICUs. PATIENTS: Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48-0.55) and 0.74 (0.69-0.77), respectively (p = 0.000). CONCLUSIONS: Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy-contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions.

The informant matters: Differences in bullying victim categorization rates assessed with self- and peer-reports in children with developmental language disorder and reading difficulties.

BACKGROUND: Children with Developmental Language Disorder (DLD) and Reading Difficulties (RD) can show more peer relation problems depending on the informant. AIMS: (1) To explore bullying victims' categorization, evaluated by self- and peer-reports, in children with DLD and RD; and (2) to assess agreement rates between informants. METHOD AND PROCEDURES: Victimization was assessed using a self-report (EBIP-Q) and a peer-report sociogram (CESC) in a sample of 83 participants (9-12 years; 10.5 ± 1.1 years), comprising of DLD (n = 19), RD (n = 32), and Control (n = 32) groups. OUTCOMES AND RESULTS: We found a higher frequency of the rejected sociometric profile in the DLD and RD groups, a higher peer-reported victimization in the DLD group, and more severe self-reported victimization in the DLD and RD groups. Odds of being classified as victimized were higher for self-report except in the DLD group. Informants' agreement was high using the most restrictive EBIP-Q criterion (7 points) for both the Control and the RD groups, being non-significant for the DLD group regardless of the criteria used. CONCLUSIONS AND IMPLICATIONS: We found a higher victimization risk in children with language difficulties, although self-assessment seems to under-detect children with DLD according to the agreement rates, pointing out the need to combine assessments and informants. WHAT DOES THIS PAPER ADD?: Several studies have shown that children with DLD or RD obtain higher scores of victimization and score lower on several scales of social skills with continuous data. Although continuous analyses are usual in research, professional decisions are usually based on cut-off criteria more than how high or low a score is in contrast to another group. This is one of the first works that analyses victimization following the cut-off criteria of self and peer assessments that professionals used in the school settings in children with DLD and RD. Our results will raise awareness among school professionals based on the evidence about the high risk of victimization, especially in children with DLD, and the implications of selecting between several measures of victimization, in this group of children. We think that our results would help to better detect and prevent bullying in schools for children with DLD.

Lack of correlation between central venous minus arterial PCO2 to arterial minus central venous O2 content ratio and respiratory quotient in patients with septic shock: A prospective observational study.

OBJECTIVE: Central venous-arterial PCO2 to arterial-central venous O2 content ratio (Pcv-aCO2/Ca-cvO2) is commonly used as a surrogate for respiratory quotient (RQ) and tissue oxygenation. Although Pcv-aCO2/Ca-cvO2 might be associated with hyperlactatemia and outcome, neither the interchangeability with RQ nor the correlation with conclusive variables of anaerobic metabolism has never been demonstrated in septic shock. Our goal was to compare Pcv-aCO2/Ca-cvO2 and RQ in patients with septic shock. DESIGN: Prospective, observational study. SETTING: Two adult ICUs. PATIENTS: Forty-seven patients with septic shock on mechanical ventilation with stable respiratory settings and vasopressor dose after initial resuscitation. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: We measured arterial and central venous gases, Hb, and O2Hb. Pcv-aCO2/Ca-cvO2 and the ratio of central venous-arterial CO2 content to arterial-central venous O2 content (Ccv-aCO2/Ca-cvO2) were calculated. RQ was determined by indirect calorimetry. RESULTS: Pcv-aCO2/Ca-cvO2 and Ccv-aCO2/Ca-cvO2 were not correlated with RQ (R2 = 0.01, P = 0.50 and R2 = 0.01, P = 0.58, respectively), showing large bias and wide 95 % limits of agreement with RQ (1.09, -1.10-3.27 and 0.42, -1.53-2.37). A multiple linear regression model showed Hb, and central venous PCO2 and O2Hb, but not RQ, as Pcv-aCO2/Ca-cvO2 determinants (R2 = 0.36, P = 0.0007). CONCLUSIONS: In patients with septic shock, Pcv-aCO2/Ca-cvO2 did not correlate with RQ and was mainly determined by factors that modify the dissociation of CO2 from Hb. Pcv-aCO2/Ca-cvO2 seems to be a poor surrogate for RQ; therefore, its values should be interpreted with caution.

Is language impaired in Spanish-speaking children with autism spectrum disorder level 1?

The current diagnostic criteria for the autism spectrum disorder (ASD) include the possibility to specify concomitant language difficulties. Purpose: Our main aim was to explore whether children with ASD-Level 1 (ASD-L1) present difficulties in the acquisition of structural language, as little work has been done in this regard so far. As a secondary aim we evaluated the degree to which the potential language impairment in ASD is directly associated with their social communication deficits or it represents a distinct deficit. Methods: To further clarify the nature and characteristics of putative language difficulties in ASD-L1, we evaluated language skills in 89 children and preadolescents diagnosed with ASD-L1, and a group of typically developing participants (TD). All of them were between 8 and 13 years old and had similar socioeconomic backgrounds. Results: Children with ASD-L1 obtained lower scores than those in TD group in repeating sentences, in finding the semantic relationships between words, and in applying word structure rules (morphology). Congruently, the core language standard score was lower in the ASD-L1 group, and the proportion of language delay was significantly higher in the ASD-L1 group than in the control group. Conclusion: Language scores were associated with autistic traits; thus, language performance in ASD-L1 is closely related to autistic symptoms. These results are discussed according to the literature on linguistic deficits in ASD-L1 and their relations with phonological working memory.

Comparison of central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio and lactate levels as predictors of mortality in critically ill patients: a systematic review and meta-analysis. / Comparação da proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central e níveis de lactato como preditores de mortalidade em pacientes críticos: uma revisão sistemática e metanálise.

OBJECTIVE: The central venousarterial carbon dioxide pressure to arterial-central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) is frequently used as a surrogate for tissue oxygenation. We aimed to identify and synthesize literature and quality of evidence supporting Pcv-aCO2/Ca-cvO2 as a predictor of mortality in critically ill patients compared with lactate. METHODS: We searched several databases for studies measuring Pcv-aCO2/Ca-cvO2 in critically ill patients. Independent investigators performed the article screening and data extraction. A random-effects metaanalysis was performed. Pooled standardized mean differences (SMD) were used to compare the prognostic ability of Pcv-aCO2/Ca-cvO2 and lactate. RESULTS: We initially retrieved 172 studies; 17 were included for qualitative description, and 10 were included for quantitative synthesis. The mean Pcv-aCO2/Ca-cvO2 was higher in nonsurvivors than in survivors (pooled SMD = 0.75; 95%CI 0.34 - 1.17; I2 = 83%), as was the case with lactate levels (pooled SMD = 0.94; 95%CI 0.34 - 1.54; I2 = 92%). Both tests were statistically significant predictors of mortality, albeit with overlapping 95%CIs between them. CONCLUSION: Moderate-quality evidence showed little or no difference in the ability of Pcv-aCO2/Ca-cvO2, compared with lactate, to predict mortality. Nevertheless, our conclusions are limited by the considerable heterogeneity among the studies.PROSPERO registration: CRD42019130387.

OBJETIVO: A proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo de oxigênio arterial menos venoso central (Pcv-aCO2/Ca-cvO2) é frequentemente usada como substituta para a oxigenação tecidual. O objetivo deste estudo foi identificar e sintetizar a literatura e a qualidade das evidências que suportam a Pcv-aCO2/Ca-cvO2 como um preditor de mortalidade em comparação com o lactato em pacientes críticos. MÉTODOS: Pesquisamos vários bancos de dados procurando estudos que tivessem medido a Pcv-aCO2/Ca-cvO2 em pacientes críticos. Pesquisadores independentes realizaram a triagem dos artigos e a extração de dados. Uma metanálise de efeitos aleatórios foi realizada. Diferenças médias padronizadas agrupadas foram usadas para comparar a capacidade prognóstica da Pcv-aCO2/Ca-cvO2 e do lactato. RESULTADOS: Inicialmente, obtivemos 172 estudos; 17 foram incluídos para descrição qualitativa, e dez foram incluídos para síntese quantitativa. A média de Pcv-aCO2/Ca-cvO2 foi maior nos não sobreviventes do que nos sobreviventes (diferença média padronizada agrupada de 0,75; IC95% 0,34 - 1,17; I2 = 83%), assim como os níveis de lactato (diferença média padronizada agrupada = 0,94; IC95% 0,34 - 1,54; I2 = 92%). Ambos os testes foram preditores estatisticamente significativos de mortalidade, embora com sobreposição de IC95% entre eles. CONCLUSÃO: Evidências de qualidade moderada mostraram pouca ou nenhuma diferença na capacidade da Pcv-aCO2/Ca-cvO2, em comparação com o lactato, em predizer mortalidade. No entanto, nossas conclusões são limitadas pela considerável heterogeneidade entre os estudos.Registro no PROSPERO: CRD42019130387.

Prehospital delay and its impact on time to treatment in ST-elevation myocardial infarction.

PURPOSES: We performed this study to assess the impact of pre-hospital time on the patient's outcome. PROCEDURES: Starting from the symptoms onset, "total time to treatment" was divided into less than or equal to 120 minutes and more than 120 minutes ("pre-hospital time" of ≤ or > 30 minutes respectively). Adverse patient's outcomes were compared in the two subgroups. FINDINGS: Our patients had a mean age of 63 (±13) years. On-scene time (17.8 ± 9.4 minutes), was the biggest fraction of "pre-hospital time". Comparing the groups with "Total time to treatment" of >120 minutes vs. ±120 minutes ("pre-hospital time" of >30 vs. ≤30 minutes), mortalities were 4 vs. 0 and transfers to a tertiary care facility were 3 vs.1. CONCLUSIONS: Most of the pre-hospital time in STEMI was spent on the scene and we suggest "total time to treatment" as a core measure instead of "door to balloon time".

Long-Term Profiles of Bullying Victims and Aggressors: A Retrospective Study.

Bullying is a widespread and worrying phenomenon, related to many different personal, behavioral, and social variables which can modulate it and its outcomes, also in the long term. These relationships are usually studied in children and adolescents, but less often in adults who have suffered or perpetrated bullying in the past. The present work explored the long-term characteristics of bullying victims and aggressors using a retrospective design. A sample of 138 adults of different ages completed an on-line protocol that included measures of bullying and victimization, substance use, sensitivity to reward and punishment, social skills, antisocial behavior, emotional regulation strategies, depression, anxiety, stress, self-esteem, and risk of suicide. The sample was divided into three groups (victims, aggressors, and controls) based on their responses to bullying-related questions. A set of Multiple Analyses of Variance with group as a fixed factor was carried out for each dependent variable. Victims and aggressors did not significantly differ in their self-reported substance consumption. Victims showed higher global depression, anxiety and stress in the past than aggressors (M = 34.66, SD = 11.74; aggressors: M = 19.70, SD = 16.53), higher emotional lack of control (M = 23.97, SD = 10.62; controls: M = 17.11, SD = 7.95) and rejection (M = 21.72, SD = 7.24; controls: M = 16.33, SD = 5.67), lower self-esteem (M = 27.72, SD = 6.70; controls: M = 31.60, SD = 6.60), and a larger frequency of suicidal thoughts (in the past) than controls. Aggressors showed higher sensitivity to reward (M = 12.03, SD = 3.66; controls: M = 8.42, SD = 3.92), larger communicational and relational skills (M = 22.10, SD = 7.20; controls: M = 17.96, SD = 7.16), and lower emotional sensitivity (M = 14.80, SD = 4.10; controls: M = 16.76, SD = 2.21). Accordingly, the logistic regression analysis identified sensitivity to reward and low psychological adjustment as the main predictors of the aggressor and victim profiles, respectively. The present results are discussed considering the extant literature on bullying and may help to improve prevention programs for this relevant social scourge.

Associations Between Self, Peer, and Teacher Reports of Victimization and Social Skills in School in Children With Language Disorders.

Previous studies have shown that teachers and parents of children with language disorders report them to have higher victimization scores, a heightened risk of low-quality friendships and social difficulties, and may be more vulnerable to peer rejection than control peers. However, there are few studies of bullying in children with developmental language disorder (DLD) and reading difficulties (RD), and none has considered the mutual relationships between teacher reports, the perceptions of classmates, and children's self-reports. We analyzed the experiences of bullying and peer relationships in primary school students with DLD and RD as compared to their age-matched peers using teacher reports, peer reports, and self-reports on victimization. Additionally, we explored how these three perspectives are associated. Results indicated lower levels of peer-rated prosocial skills in DLD and RD students compared to their peers, as well as higher levels of victimization as assessed by peers for students with DLD. In the same line, the teachers' ratings showed that students with DLD presented poorer social skills, less adaptability, and more withdrawal in social interaction. Contrastingly, self-reports informed of similar rates of interpersonal relationships, social stress, and peer victimization between the three groups. Consequently, we found significant correlations between measures of peer reports and teacher reports that contrasted with the lack of correlations between self and other agents' reports. These findings stress the importance of using self-reports, peer reports, and teacher reports at the same time to detect bullying situations that might go unnoticed.

California Bullying Victimization Scale-Retrospective (CBVS-R): Validation of the Spanish Adaptation.

BACKGROUND: Bullying in childhood and adolescence is a worldwide problem. There is a general lack of validated retrospective measures of bullying, especially in Spanish-speaking populations. The present study aimed to adapt the retrospective version of the California Bullying Victimization Scale (CBVS-R) to Spanish and examine its psychometric properties. METHOD: The CBVS-R was translated and adapted into Spanish, and school victimization was evaluated in a sample of 1,855 Spanish adults (69.3% women). Factor structure, test-retest reliability, and predictive validity were explored. The types of victimization by educational level and the total victimization score for each participant were analyzed. RESULTS: Factor analysis showed a one-factor structure. Values of internal consistency (α = .80) and test-retest reliability ( r = .87, k = .73) were satisfactory. Victimization was associated with self-reports of mental health. Victimization patterns peaked around adolescence, the most frequent victimizing behavior was being teased or called names. CONCLUSIONS: Results support the usefulness and suitability of the Spanish adaptation of the CBVS-R as a retrospective self-report measure of bullying victimization in adults.

Central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio as an indicator of tissue oxygenation: a narrative review. / Proporção entre pressão venosa central menos arterial de dióxido de carbono e conteúdo arterial menos venoso central de oxigênio como indicador de oxigenação tissular: uma revisão narrativa.

The central venous minus arterial carbon dioxide pressure to arterial minus central venous oxygen content ratio (Pcv-aCO2/Ca-cvO2) has been proposed as a surrogate for respiratory quotient and an indicator of tissue oxygenation. Some small observational studies have found that a Pcv-aCO2/Ca-cvO2 > 1.4 was associated with hyperlactatemia, oxygen supply dependency, and increased mortality. Moreover, Pcv-aCO2/Ca-cvO2 has been incorporated into algorithms for tissue oxygenation evaluation and resuscitation. However, the evidence for these recommendations is quite limited and of low quality. The goal of this narrative review was to analyze the methodological bases, the pathophysiologic foundations, and the experimental and clinical evidence supporting the use of Pcv-aCO2/Ca-cvO2 as a surrogate for respiratory quotient. Physiologically, the increase in respiratory quotient secondary to critical reductions in oxygen transport is a life-threatening and dramatic event. Nevertheless, this event is easily noticeable and probably does not require further monitoring. Since the beginning of anaerobic metabolism is indicated by the sudden increase in respiratory quotient and the normal range of respiratory quotient is wide, the use of a defined cutoff of 1.4 for Pcv-aCO2/Ca-cvO2 is meaningless. Experimental studies have shown that Pcv-aCO2/Ca-cvO2 is more dependent on factors that modify the dissociation of carbon dioxide from hemoglobin than on respiratory quotient and that respiratory quotient and Pcv-aCO2/Ca-cvO2 may have distinct behaviors. Studies performed in critically ill patients have shown controversial results regarding the ability of Pcv-aCO2/Ca-cvO2 to predict outcome, hyperlactatemia, microvascular abnormalities, and oxygen supply dependency. A randomized controlled trial also showed that Pcv-aCO2/Ca-cvO2 is useless as a goal of resuscitation. Pcv-aCO2/Ca-cvO2 should be carefully interpreted in critically ill patients.

Behavioral, Emotional and School Adjustment in Adolescents with and without Developmental Language Disorder (DLD) Is Related to Family Involvement.

Developmental language disorder (DLD) refers to a language delay in the absence of other underlying causes. Individuals with DLD can also present other problems related to behavioral, scholarly, and emotional aspects of their daily lives because of their language difficulties. Moreover, these difficulties could be influenced by family and socioeconomic characteristics. Twenty-eight bilingual adolescents with and without DLD in typical schools were followed from childhood to adolescence. At age five, language and cognitive variables were assessed. In addition, language, behavior, emotional and school adjustment, and socioeconomic and family aspects were evaluated at age 12. Results reveal that adolescents with DLD show poorer school adjustment and less adaptive skills when evaluated by their tutors, and a larger index of emotional problems when self-assessed. Moreover, family involvement, but not socioeconomic status (SES), emerged as a protective factor since it was related to behavioral, emotional, and school adjustment, a result that was further confirmed by structural equation modeling. Therefore, a more global approach involving individuals, schools and families is needed to provide adolescents with DLD adequate support. It is important to stimulate their social skills and emotional adjustment so they can cope with social difficulties more easily, especially at school.

Characteristics of resuscitation, and association between use of dynamic tests of fluid responsiveness and outcomes in septic patients: results of a multicenter prospective cohort study in Argentina.

BACKGROUND: Resuscitation of septic patients regarding goals, monitoring aspects and therapy is highly variable. Our aim was to characterize cardiovascular and fluid management of sepsis in Argentina, a low and middle-income country (LMIC). Furthermore, we sought to test whether the utilization of dynamic tests of fluid responsiveness, as a guide for fluid therapy after initial resuscitation in patients with persistent or recurrent hypoperfusion, was associated with decreased mortality. METHODS: Secondary analysis of a national, multicenter prospective cohort study (n = 787) fulfilling Sepsis-3 definitions. Epidemiological characteristics, hemodynamic management data, type of fluids and vasopressors administered, physiological variables denoting hypoperfusion, use of tests of fluid responsiveness, and outcomes, were registered. Independent predictors of mortality were identified with logistic regression analysis. RESULTS: Initially, 584 of 787 patients (74%) had mean arterial pressure (MAP) < 65 mm Hg and/or signs of hypoperfusion and received 30 mL/kg of fluids, mostly normal saline (53%) and Ringer lactate (35%). Vasopressors and/or inotropes were administered in 514 (65%) patients, mainly norepinephrine (100%) and dobutamine (9%); in 22%, vasopressors were administered before ending the fluid load. After this, 413 patients (53%) presented persisting or recurrent hypotension and/or hypoperfusion, which prompted administration of additional fluid, based on: lactate levels (66%), urine output (62%), heart rate (54%), central venous O2 saturation (39%), central venous-arterial PCO2 difference (38%), MAP (31%), dynamic tests of fluid responsiveness (30%), capillary-refill time (28%), mottling (26%), central venous pressure (24%), cardiac index (13%) and/or pulmonary wedge pressure (3%). Independent predictors of mortality were SOFA and Charlson scores, lactate, requirement of mechanical ventilation, and utilization of dynamic tests of fluid responsiveness. CONCLUSIONS: In this prospective observational study assessing the characteristics of resuscitation of septic patients in Argentina, a LMIC, the prevalent use of initial fluid bolus with normal saline and Ringer lactate and the use of norepinephrine as the most frequent vasopressor, reflect current worldwide practices. After initial resuscitation with 30 mL/kg of fluids and vasopressors, 413 patients developed persistent or recurrent hypoperfusion, which required further volume expansion. In this setting, the assessment of fluid responsiveness with dynamic tests to guide fluid resuscitation was independently associated with decreased mortality.

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study.

INTRODUCTION: Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation. METHODS: Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO2 and VO2), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO2 difference (DeltaPCO2). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated. RESULTS: Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO2 and VO2, lactate, albumin-corrected anion gap, and DeltaPCO2 remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 +/- 0.7, 2.2 +/- 0.7, 2.0 +/- 0.8) and the percent of perfused capillaries (72 +/- 26, 71 +/- 27, 67 +/- 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 +/- 10,17 +/- 10,14 +/- 2 vessels/mm2, respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R2 = 0.95, P < 0.0001). CONCLUSIONS: Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.

Effects of short-term hyperoxia on sytemic hemodynamics, oxygen transport, and microcirculation: An observational study in patients with septic shock and healthy volunteers.

PURPOSE: To characterize the microvascular effects of a brief period of hyperoxia, in patients with septic shock and in healthy volunteers. MATERIALS AND METHODS: In 20 patients with septic shock, we assessed systemic hemodynamics, sublingual microcirculation by SDF-videomicroscopy, and skin perfusion by capillary refill time (CRT), central-peripheral temperature (ΔT°), and perfusion index. Measurements were performed at baseline and after 5 min of inspired oxygen fraction of 1.00. Additionally, we studied 8 healthy volunteers, in whom hyperoxia was prolonged to 30 min. RESULTS: In septic patients, hyperoxia increased mean arterial pressure and systemic vascular resistance, but cardiac output remained unchanged. The only significant change in sublingual microcirculation was a decreased heterogeneity flow index (1.03 [1.01-1.07] vs 1.01 [0.34-1.05], P = .002). Perfused vascular density (13.1 [12.0-15.0] vs 14.0 [12.2-14.8] mm/mm2, P = .21) and the other sublingual microvascular variables were unmodified. CRT and ΔT° did not change but perfusion index slightly decreased. In healthy volunteers, sublingual microcirculation and skin perfusion were stable. CONCLUSIONS: Short-term hyperoxia induced systemic cardiovascular changes but was not associated with noticeable derangement in sublingual microcirculation and skin perfusion. Nevertheless, longer exposures to hyperoxia might have produced different results.

Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia.

OBJECTIVE: To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. DESIGN: Controlled experimental study. SETTING: University-based research laboratory. SUBJECTS: A total of 14 anesthetized, mechanically ventilated sheep. INTERVENTIONS: Sheep were randomly assigned to endotoxin (n = 7) or control groups (n = 7). The endotoxin group received 5 microg/kg endotoxin, followed by 4 microg x kg(-1) x hr(-1) for 150 mins. After 60 mins of shock, hydroxyethylstarch resuscitation was given to normalize oxygen transport for an additional 90 mins. MEASUREMENTS AND MAIN RESULTS: Endotoxin infusion decreased mean arterial blood pressure, cardiac output, and superior mesenteric artery blood flow (96 +/- 10 vs. 51 +/- 20 mm Hg, 145 +/- 30 vs. 90 +/- 30 mL x min(-1) x kg(-1), and 643 +/- 203 vs. 317 +/- 93 mL x min(-1) x kg(-1), respectively; p < .05 vs. basal), whereas it increased intramucosal-arterial PCO2 (deltaPCO2) and arterial lactate (3 +/- 3 vs. 14 +/- 8 mm Hg, and 1.5 +/- 0.5 vs. 3.7 +/- 1.3 mmol/L; p < .05). Sublingual, and serosal and mucosal intestinal microvascular flow indexes, and the percentage of perfused ileal villi were reduced (3.0 +/- 0.1 vs. 2.3 +/- 0.4, 3.2 +/- 0.2 vs. 2.4 +/- 0.6, 3.0 +/- 0.0 vs. 2.0 +/- 0.2, and 98% +/- 3% vs. 76% +/- 10%; p < .05). Resuscitation normalized mean arterial blood pressure (92 +/- 13 mm Hg), cardiac output (165 +/- 32 mL x min(-1) x kg(-1)), superior mesenteric artery blood flow (683 +/- 192 mL x min(-1) x kg(-1)), and sublingual and serosal intestinal microvascular flow indexes (2.8 +/- 0.5 and 3.5 +/- 0.7). Nevertheless, deltaPCO2, lactate, mucosal intestinal microvascular flow indexes, and percentage of perfused ileal villi remained altered (10 +/- 6 mm Hg, 3.7 +/- 0.9 mmol/L, 2.3 +/- 0.4, and 78% +/- 11%; p < .05). CONCLUSIONS: In this model of endotoxemia, fluid resuscitation corrected both serosal intestinal and sublingual microcirculation but was unable to restore intestinal mucosal perfusion. Intramucosal acidosis might be due to persistent villi hypoperfusion.

Poor agreement in the calculation of venoarterial PCO2 to arteriovenous O2 content difference ratio using central and mixed venous blood samples in septic patients.

PURPOSE: Central venous minus arterial PCO2 to arterial minus central venous O2 content difference ratio (Pcv-aCO2/Ca-cvO2) has been proposed as a clinical surrogate for respiratory quotient. Our goal was to assess its interchangeability with mixed venous minus arterial PCO2 to arterial minus mixed venous O2 content difference ratio (Pmv-aCO2/Ca-mvO2). MATERIALS AND METHODS: This is a subanalysis of a previously published study. We studied 23 septic patients who had an indwelling Swan-Ganz catheter. The agreement between Pcv-aCO2/Ca-cvO2 and Pmv-aCO2/Ca-mvO2 was evaluated by Bland and Altman analysis. We also performed linear regression analysis with Pmv-aCO2/Ca-mvO2 as the dependent variable. RESULTS: 95% limits of agreement between Pcv-aCO2/Ca-cvO2 and Pmv-aCO2/Ca-mvO2 were 1.48. Pmv-aCO2/Ca-mvO2 was significantly correlated with hemoglobin and lactate (R2 = 0.48 and 0.31, respectively, P < 0.01 for both). CONCLUSIONS: In this study, Pcv-aCO2/Ca-cvO2 and Pmv-aCO2/Ca-mvO2 were not interchangeable. In addition, Pmv-aCO2/Ca-mvO2 is a composite variable, which depends on several determinants. Values of Pcv-aCO2/Ca-cvO2 should be cautiously interpreted in the assessment of critically ill patients.