Heparin Therapy Improving Hypoxia in COVID-19 Patients - A Case Series.

INTRODUCTION: Elevated D-dimer is a predictor of severity and mortality in COVID-19 patients, and heparin use during in-hospital stay has been associated with decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting that hypercoagulability is a prominent feature of organ failure in these patients. Interestingly, in COVID-19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. METHODS: We describe a series of 27 consecutive COVID-19 patients admitted to Sirio-Libanes Hospital in São Paulo-Brazil and treated with heparin in therapeutic doses tailored to clinical severity. RESULTS: PaO2/FiO2 ratio increased significantly over the 72 h following the start of anticoagulation, from 254(±90) to 325(±80), p = 0.013, and 92% of the patients were discharged home within a median time of 11 days. There were no bleeding complications or fatal events. DISCUSSION: Even though this uncontrolled case series does not offer absolute proof that micro thrombosis in the pulmonary circulation is the underlying mechanism of respiratory failure in COVID-19, patient's positive response to heparinization contributes to the understanding of the pathophysiological mechanism of the disease and provides valuable information for the treatment of these patients while we await the results of further prospective controlled studies.

Heparin therapy improving hypoxia in COVID-19 patients - a case series [preprint]

INTRODUCTION: Elevated D-dimer is predictor of severity and mortality in COVID-19 patients and heparin use during in hospital stay has been associated to decreased mortality. COVID-19 patient autopsies have revealed thrombi in the microvasculature, suggesting intravascular coagulation as a prominent feature of organ failure in these patients. Interestingly, in COVID19, pulmonary compliance is preserved despite severe hypoxemia corroborating the hypothesis that perfusion mismatch may play a significant role in the development of respiratory failure. METHODS: We describe a series of 27 consecutive COVID-19 patients admitted to the Pulmonology service at Sirio-Libanes Hospital in São Paulo-Brazil treated with heparin in therapeutic doses tailored to clinical severity. RESULTS: PaO2/FiO2 ratio increased significantly over the 72 hours following the start of anticoagulation, from 254(±90) to 325(±80), p=0.013, and over half of the patients were discharged home within an average time of 7.3 (±4.0) days. Half of mechanically ventilated patients were extubated within 10.3 (±1.5) days. The remaining patients showed progressive improvement and there were no bleeding complications or fatal events. DISCUSSION: Even though this uncontrolled case series does not offer absolute proof of DIC as the underlying mechanism of respiratory failure in COVID-19, as well as patients positive response to tailored dose heparinization, it contributes to the understanding of the physiopathological mechanism of the disease and provides valuable information for the treatment of these very sick patients while we await the results of further prospective controlled studies

Pentraxin 3 accelerates lung injury in high tidal volume ventilation in mice.

Mechanical ventilation is the major cause of iatrogenic lung damage in intensive care units. Although inflammation is known to be involved in ventilator-induced lung injury (VILI), several aspects of this process are still unknown. Pentraxin 3 (PTX3) is an acute phase protein with important regulatory functions in inflammation which has been found elevated in patients with acute respiratory distress syndrome. This study aimed at investigating the direct effect of PTX3 production in the pathogenesis of VILI. Genetically modified mice deficient and that over express murine Ptx3 gene were subjected to high tidal volume ventilation (V(T)=45 mL/kg, PEEP(zero)). Morphological changes and time required for 50% increase in respiratory system elastance were evaluated. Gene expression profile in the lungs was also investigated in earlier times in Ptx3-overexpressing mice. Ptx3 knockout and wild-type mice developed same lung injury degree in similar times (156±42 min and 148±41 min, respectively; p=0.8173). However, Ptx3 over-expression led to a faster development of VILI in Ptx3-overexpressing mice (77±29 min vs 118±41 min, p=0.0225) which also displayed a faster kinetics of Il1b expression and elevated Ptx3, Cxcl1 and Ccl2 transcripts levels in comparison with wild-type mice assessed by quantitative real-time polymerase chain reaction. Ptx3 deficiency did not impacted the time for VILI induced by high tidal volume ventilation but Ptx3-overexpression increased inflammatory response and reflected in a faster VILI development.

Cholinergic hyperresponsiveness of peripheral lung parenchyma in chronic obstructive pulmonary disease.

BACKGROUND: Up to 60% of chronic obstructive pulmonary disease (COPD) patients can present airway hyperresponsiveness. However, it is not known whether the peripheral lung tissue also shows an exaggerated response to agonists in COPD. OBJECTIVES: To investigate the in vitro mechanical behavior and the structural and inflammatory changes of peripheral lung tissue in COPD patients and compare to nonsmoking controls. METHODS: We measured resistance and elastance at baseline and after acetylcholine (ACh) challenge of lung strips obtained from 10 COPD patients and 10 control subjects. We also assessed the alveolar tissue density of neutrophils, eosinophils, macrophages, mast cells and CD8+ and CD4+ cells, as well as the content of α-smooth muscle actin-positive cells and elastic and collagen fibers. We further investigated whether changes in in vitro parenchymal mechanics correlated to structural and inflammatory parameters and to in vivo pulmonary function. RESULTS: Values of resistance after ACh treatment and the percent increase in tissue resistance (%R) were higher in the COPD group (p ≤ 0.03). There was a higher density of macrophages and CD8+ cells (p < 0.05) and a lower elastic content (p = 0.003) in the COPD group. We observed a positive correlation between %R and eosinophil and CD8+ cell density (r = 0.608, p = 0.002, and r = 0.581, p = 0.001, respectively) and a negative correlation between %R and the ratio of forced expiratory volume in 1 s to forced vital capacity (r = -0.451, p < 0.05). CONCLUSIONS: The cholinergic responsiveness of parenchymal lung strips is increased in COPD patients and seems to be related to alveolar tissue eosinophilic and CD8 lymphocytic inflammation and to the degree of airway obstruction on the pulmonary function test.

Respiratory support withdrawal in intensive care units: families, physicians and nurses views on two hypothetical clinical scenarios.

INTRODUCTION: Evidence suggests that dying patients' physical and emotional suffering is inadequately treated in intensive care units. Although there are recommendations regarding decisions to forgo life-sustaining therapy, deciding on withdrawal of life support is difficult, and it is also difficult to decide who should participate in this decision. METHODS: We distributed a self-administered questionnaire in 13 adult intensive care units (ICUs) assessing the attitudes of physicians and nurses regarding end-of-life decisions. Family members from a medical-surgical ICU in a tertiary cancer hospital were also invited to participate. Questions were related to two hypothetical clinical scenarios, one with a competent patient and the other with an incompetent patient, asking whether the ventilator treatment should be withdrawn and about who should make this decision. RESULTS: Physicians (155) and nurses (204) of 12 ICUs agreed to take part in this study, along with 300 family members. The vast majority of families (78.6%), physicians (74.8%) and nurses (75%) want to discuss end-of-life decisions with competent patients. Most of the physicians and nurses desire family involvement in end-of-life decisions. Physicians are more likely to propose withdrawal of the ventilator with competent patients than with incompetent patients (74.8% × 60.7%, P = 0.028). When the patient was incompetent, physicians (34.8%) were significantly less prone than nurses (23.0%) and families (14.7%) to propose decisions regarding withdrawal of the ventilator support (P < 0.001). CONCLUSIONS: Physicians, nurses and families recommended limiting life-support therapy with terminally ill patients and favored family participation. In decisions concerning an incompetent patient, physicians were more likely to maintain the therapy.

Assessment of pulmonary function and quality of life in patients submitted to pulmonary resection for cancer.

OBJECTIVE: To evaluate the effects that pulmonary resection has on pulmonary function and quality of life (QoL) in patients with primary or metastatic lung cancer. METHODS: This was a prospective cohort study involving all patients submitted to pulmonary resection for cancer between September of 2006 and March of 2007 at the A. C. Camargo Hospital in São Paulo, Brazil. Patients underwent spirometry in the preoperative period and at six months after the surgical procedure. After a postoperative period of six months, the patients completed an overall QoL questionnaire (the Medical Outcomes Study 36-item Short-form Health Survey) and another one, specific for respiratory symptoms (the Saint George's Respiratory Questionnaire). The scores obtained in our study were compared with those previously obtained for a general population and for a population of patients with COPD. RESULTS: We included 33 patients (14 males and 19 females), ranging in age from 39 to 79 years. All of the patients, smokers and nonsmokers alike, presented significant worsening of pulmonary function. The mean scores on the overall QoL questionnaire were approximately 5% lower than those obtained for the general population. The scores of various domains of the symptom-specific QoL questionnaire were 50-60% lower than those obtained for the general population and approximately 20% higher than those obtained for the population with COPD. CONCLUSIONS: Pulmonary resection has a direct negative impact on pulmonary function and QoL, especially on the QoL related to aspects directly linked to pulmonary function. We highlight the importance of preoperative assessment of pulmonary function in patients undergoing pulmonary resection, in order to predict their postoperative evolution.

Avaliação da função pulmonar e da qualidade de vida em pacientes submetidos à ressecção pulmonar por neoplasia / Assessment of pulmonary function and quality of life in patients submitted to pulmonary resection for cancer

OBJETIVO: Avaliar as repercussões da ressecção pulmonar sobre a função pulmonar e a qualidade de vida (QV) de pacientes com câncer de pulmão primário ou metastático. MÉTODOS: Estudo de coorte prospectivo que incluiu todos os pacientes que realizaram ressecção pulmonar por neoplasia no Hospital A. C. Camargo entre setembro de 2006 e março de 2007. Os pacientes foram avaliados no pré-operatório e após seis meses do procedimento cirúrgico através de espirometria. Após seis meses de pós-operatório, os pacientes responderam a um questionário de QV geral (Medical Outcomes Study 36-item Short-form Health Survey) e um específico para sintomas respiratórios (Saint George's Respiratory Questionnaire). Os valores de QV obtidos foram comparados a valores de uma população geral e aos de uma população de portadores de DPOC. RESULTADOS: Foram incluídos 33 pacientes (14 homens e 19 mulheres), com idade entre 39 e 79 anos. Todos os pacientes, tabagistas ou não, apresentaram piora significativa da função pulmonar. Observamos uma redução de aproximadamente 5 por cento na média dos escores do questionário de QV geral em comparação àquela da população geral. Houve uma redução de 50-60 por cento nos vários domínios do questionário específico para sintomas, quando comparado aos resultados da população geral, e um aumento de aproximadamente 20 por cento, quando comparado aos resultados da população com DPOC. CONCLUSÕES: Existe impacto direto da ressecção pulmonar na deterioração da função pulmonar e na QV com ênfase nos aspectos diretamente ligados à função pulmonar. Cabe ressaltar a importância da avaliação da função pulmonar destes pacientes no pré-operatório para se estimar sua evolução pós-cirúrgica.

OBJECTIVE: To evaluate the effects that pulmonary resection has on pulmonary function and quality of life (QoL) in patients with primary or metastatic lung cancer. METHODS: This was a prospective cohort study involving all patients submitted to pulmonary resection for cancer between September of 2006 and March of 2007 at the A. C. Camargo Hospital in São Paulo, Brazil. Patients underwent spirometry in the preoperative period and at six months after the surgical procedure. After a postoperative period of six months, the patients completed an overall QoL questionnaire (the Medical Outcomes Study 36-item Short-form Health Survey) and another one, specific for respiratory symptoms (the Saint George's Respiratory Questionnaire). The scores obtained in our study were compared with those previously obtained for a general population and for a population of patients with COPD. RESULTS: We included 33 patients (14 males and 19 females), ranging in age from 39 to 79 years. All of the patients, smokers and nonsmokers alike, presented significant worsening of pulmonary function. The mean scores on the overall QoL questionnaire were approximately 5 percent lower than those obtained for the general population. The scores of various domains of the symptom-specific QoL questionnaire were 50-60 percent lower than those obtained for the general population and approximately 20 percent higher than those obtained for the population with COPD. CONCLUSIONS: Pulmonary resection has a direct negative impact on pulmonary function and QoL, especially on the QoL related to aspects directly linked to pulmonary function. We highlight the importance of preoperative assessment of pulmonary function in patients undergoing pulmonary resection, in order to predict their postoperative evolution.

Family members of critically ill cancer patients: assessing the symptoms of anxiety and depression.

OBJECTIVE: To determine prevalence and factors associated with symptoms of anxiety and depression in family members of critically ill cancer patients. DESIGN: Prospective cohort study. SETTING: A 23-bed intensive care unit in a tertiary cancer centre. PATIENTS AND PARTICIPANTS: Three hundred consecutive families of cancer patients with length of stay >72 h in ICU. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The Hospital Anxiety and Depression Scale questionnaire and critical care family needs inventory were completed by family members. Prevalence of anxiety and depression in family members was 71 and 50.3%, respectively. Regarding the patients' disease, family depression was correlated with presence of metastasis, whereas hematological malignancies correlated with family' anxiety. Anxiety was independently associated with one patient-related factor (prolonged mechanical ventilation) and two family-related factors (catholic religion and gender). Factors associated with symptoms of depression included one patient-related factor (presence of metastasis) and one family-related factor (gender). CONCLUSIONS: Present findings demonstrated a high prevalence of anxiety and depression in critically ill cancer patients' family members during an intensive care unit stay.

Saline instillation before tracheal suctioning decreases the incidence of ventilator-associated pneumonia.

OBJECTIVES: To compare the incidence of ventilator-associated pneumonia (VAP) with or without isotonic saline instillation before tracheal suctioning. As a secondary objective, we compared the incidence of endotracheal tube occlusion and atelectasis. DESIGN: Randomized clinical trial. SETTING AND PATIENTS: The study was conducted in a medical surgical intensive care unit of an oncologic hospital. We selected consecutive patients needing mechanical ventilation for >72 hrs. Patients were allocated into two groups: a saline group that received instillation of 8 mL of saline before tracheal suctioning and a control group which did not. VAP was diagnosed based on clinical suspicion and confirmed by bronchoalveolar lavage quantitative culture. The incidence of atelectasis on daily chest radiography and endotracheal tube occlusions were recorded. The sample size was calculated to a power of 80% and a type I error probability of 5%. MEASUREMENTS AND MAIN RESULTS: One hundred thirty patients were assigned to the saline group and 132 to the control group. The baseline demographic variables were similar between groups. The rate of clinically suspected VAP was similar in both groups. The incidence of microbiological proven VAP was significantly lower in the saline group (23.5% x 10.8%; p = 0.008) (incidence density/1.000 days of ventilation 21.22 x 9.62; p < 0.01). Using the Kaplan-Meier curve analysis, the proportion of patients remaining without VAP was higher in the saline group (p = 0.02, log-rank test). The relative risk reduction of VAP in the saline instillation group was 54% (95% confidence interval, 18%-74%) and the number needed to treat was eight (95% confidence interval, 5-27). The incidence of atelectases and endotracheal tube occlusion were similar between groups. CONCLUSIONS: Instillation of isotonic saline before tracheal suctioning decreases the incidence of microbiological proven VAP.

Noninvasive ventilation in immunocompromised pediatric patients: eight years of experience in a pediatric oncology intensive care unit.

OBJECTIVE: The experience of noninvasive positive pressure ventilation (NPPV) in the pediatric setting is limited. The aim of the present study is to retrospectively evaluate the effectiveness of NPPV in pediatric immunocompromised patient admitted in our PICU (Pediatric Intensive Care Unit) for acute respiratory failure. DESIGN/SETTING: Retrospective cohort study of children admitted to the PICU of Hospital do Cancer between June 1997 and May 2005 requiring ventilatory support. RESULTS: A total of 239 admissions were included. The first mechanical ventilation (MV) technique used was NPPV in 120 (50.2%) patients [noninvasive ventilation (NIV) group] and conventional MV in 119 (49.8%) [invasive ventilation (IV) group]; 25.8% of the patients from the NIV group subsequently required intubation. Patients in the IV group were more likely to be in a severe clinical status. Characteristics associated with severe clinical status were median value for therapeutic intervention scoring system score (37.5 points IV vs. 29 points NIV, P<0.0001), presence of >2 organs failure (63.6% IV vs. 36.4% NIV, P<0.0001), cardiac failure (62.5% IV vs. 37.5% NIV, P<0.0001), and septic shock (63.9% IV vs. 36.1% NIV, P<0.0001). Documented severe pulmonary disease was significantly higher (67.6%) in IV group, P=0.02. Baseline values of arterial pCO2, hypoxemia, arterial pH, and respiratory rate did not differ between the groups. Multivariate analysis showed that independent predictive factors for intubation were solid tumors (P=0.012), cardiovascular dysfunction (P<0.0001), and therapeutic intervention scoring system score >or=40 points (P=0.018). CONCLUSIONS: Our results encourage the use of NPPV as a first-line treatment in children with malignancies who develops acute respiratory failure, except in those with severe hemodynamic status.

Families' interactions with physicians in the intensive care unit: the impact on family's satisfaction.

PURPOSE: The objective of this study is to correlate the levels of satisfaction of family members, with their perception of the way information was offered and assistance delivered during the patient's stay in the intensive care unit (ICU). MATERIALS AND METHODS: This is a prospective study conducted in a 13-bed mixed ICU in a tertiary cancer. Family members were enrolled 2 days after admission if the patient remained in the ICU. Questions derived from a previous study assessed the quality of the information and support received (Crit Care Med 1998; 26:1187). To generate the satisfaction criteria, families fulfilled a Portuguese version of the Critical Care Family Needs Inventory. RESULTS: One hundred sixty-four families were interviewed between May 2002 and May 2003. Insufficient information concerning the consequences of disease was a determinant of dissatisfaction (odds ratio [OR], 3.35; confidence interval [CI], 1.3-8.8), as well as insufficient information given by the ICU doctors (OR, 3.85; CI, 1.2-12.2). Accessibility of doctors was a major determinant of dissatisfaction when considered inadequate (OR, 6.92; CI, 2.3-20.6), and it was associated to a conflict regarding prognosis (P = .017). CONCLUSION: Family satisfaction and understanding in the ICU may improve if the doctors are more accessible to provide information and the staff strive to better explain the patient's condition.

Trend of maximal inspiratory pressure in mechanically ventilated patients: predictors.

INTRODUCTION: It is known that mechanical ventilation and many of its features may affect the evolution of inspiratory muscle strength during ventilation. However, this evolution has not been described, nor have its predictors been studied. In addition, a probable parallel between inspiratory and limb muscle strength evolution has not been investigated. OBJECTIVE: To describe the variation over time of maximal inspiratory pressure during mechanical ventilation and its predictors. We also studied the possible relationship between the evolution of maximal inspiratory pressure and limb muscle strength. METHODS: A prospective observational study was performed in consecutive patients submitted to mechanical ventilation for > 72 hours. The maximal inspiratory pressure trend was evaluated by the linear regression of the daily maximal inspiratory pressure and a logistic regression analysis was used to look for independent maximal inspiratory pressure trend predictors. Limb muscle strength was evaluated using the Medical Research Council score. RESULTS: One hundred and sixteen patients were studied, forty-four of whom (37.9%) presented a decrease in maximal inspiratory pressure over time. The members of the group in which maximal inspiratory pressure decreased underwent deeper sedation, spent less time in pressure support ventilation and were extubated less frequently. The only independent predictor of the maximal inspiratory pressure trend was the level of sedation (OR=1.55, 95% CI 1.003 - 2.408; p = 0.049). There was no relationship between the maximal inspiratory pressure trend and limb muscle strength. CONCLUSIONS: Around forty percent of the mechanically ventilated patients had a decreased maximal inspiratory pressure during mechanical ventilation, which was independently associated with deeper levels of sedation. There was no relationship between the evolution of maximal inspiratory pressure and the muscular strength of the limb.

Trend of maximal inspiratory pressure in mechanically ventilated patients: predictors

INTRODUCTION: It is known that mechanical ventilation and many of its features may affect the evolution of inspiratory muscle strength during ventilation. However, this evolution has not been described, nor have its predictors been studied. In addition, a probable parallel between inspiratory and limb muscle strength evolution has not been investigated. OBJECTIVE: To describe the variation over time of maximal inspiratory pressure during mechanical ventilation and its predictors. We also studied the possible relationship between the evolution of maximal inspiratory pressure and limb muscle strength. METHODS: A prospective observational study was performed in consecutive patients submitted to mechanical ventilation for > 72 hours. The maximal inspiratory pressure trend was evaluated by the linear regression of the daily maximal inspiratory pressure and a logistic regression analysis was used to look for independent maximal inspiratory pressure trend predictors. Limb muscle strength was evaluated using the Medical Research Council score. RESULTS: One hundred and sixteen patients were studied, forty-four of whom (37.9 percent) presented a decrease in maximal inspiratory pressure over time. The members of the group in which maximal inspiratory pressure decreased underwent deeper sedation, spent less time in pressure support ventilation and were extubated less frequently. The only independent predictor of the maximal inspiratory pressure trend was the level of sedation (OR=1.55, 95 percent CI 1.003 - 2.408; p = 0.049). There was no relationship between the maximal inspiratory pressure trend and limb muscle strength. CONCLUSIONS: Around forty percent of the mechanically ventilated patients had a decreased maximal inspiratory pressure during mechanical ventilation, which was independently associated with deeper levels of sedation. There was no relationship between the evolution of maximal inspiratory pressure and the muscular strength of the limb.

Late echocardiography assessment of systolic and diastolic function of the left ventricle in pediatric cancer survivors after anthracycline therapy.

BACKGROUND: The usefulness of daunorubicin (DAUNO) and doxorubicin, members of the anthracycline class of anticancer drugs, is limited by their cardiotoxicity. The purpose of our echocardiographic study was to assess the left ventricular (LV) function in long-term pediatric cancer survivors who had received DAUNO and dox as part of their therapy. PATIENTS AND METHODS: Seventy patients and 70 age, sex, and body surface area matched healthy controls were evaluated. Among the patients, the mean cumulative anthracycline dose was 321.6 (range, 150 to 868 mg/m); the mean interval from cancer diagnosis to evaluation was 13.9 years (range, 7 to 30 y). RESULTS: Fifteen of the 70 (21.4%) patients had a reduced ejection fraction (EF). Compared with the healthy controls, the mean EF and E/A were decreased to low normal levels in the patients, whereas deceleration time and isovolumetric relaxation time were prolonged. The E/A and deceleration time were significantly different for the females but not the males. The Tissue Doppler Index was normal but the Myocardial Performance Index was prolonged and correlated with EF (r=-0.499, P<0.001). There was a correlation between EF with cumulative anthracycline dose (r=-0.306; P=0.010) and time off therapy (r=-0.281; P=0.019). Diastolic indices suggested a tendency toward abnormal LV relaxation. Myocardial Performance Index seems to be a good index for monitoring LV status, because it was prolonged as EF decreased. CONCLUSIONS: This study suggests that long-term survivors who received doxorubicin and DAUNO may be found to have subclinical features of myocardial dysfunction when evaluated years after the completion of therapy.