Michael Darmon

Prognosis of Lung Cancer Patients With Life-Threatening Complications

BACKGROUNDnThe management of patients with lung cancer has improved recently, and many of them will require admission to the ICU. The aims of this study were to determine hospital mortality and to identify risk factors for death in a large cohort of critically ill patients.nnnMETHODSnCohort study in two ICUs specialized in the management of patients with cancer, in France and Brazil.nnnRESULTSnOf the 143 patients (mean age, 61.6 +/- 9.9 years [+/- SD]), 25 patients (17%) had small cell lung cancer and 118 patients (83%) had non-small cell lung cancer. The main reasons for ICU admission were sepsis (44%) and acute respiratory failure (31%). Mechanical ventilation (MV) was used in 100 patients (70%), including 38 patients in whom lung cancer was considered a reason for MV. Hospital mortality was 59% overall and 69% in patients receiving MV. By multivariate logistic regression, airway infiltration or obstruction by cancer, number of organ failures, cancer recurrence or progression, and severity of comorbidities were associated with increased mortality.nnnCONCLUSIONSnThe improved survival previously reported in patients with cancer admitted to the ICU seems to extend to patients with lung cancer, including those who need MV. Mortality increased with the number of organ failures, severity of comorbidities, and presence of respiratory failure due to cancer progression. The type of the cancer per se was not associated with mortality and, therefore, should not be factored into ICU triage decisions.

Síndrome de lise tumoral: uma revisão abrangente da literatura

Tumor lysis syndrome is characterized by the massive destruction of malignant cells and the release in the extra-cellular space of their content. While Tumor lysis syndrome may occur spontaneously before treatment, it usually develops shortly after the initiation of cytotoxic chemotherapy. These metabolites can overwhelm the homeostatic mechanisms with development of hyperuricaemia, hyperkalaemia, hyperphosphataemia, and hypocalcaemia. These biological manifestations may lead to clinical manifestations including, acute kidney injury, seizure, or sudden death that require intensive care. Since clinical tumor lysis syndrome is associated with a poor prognosis both prevention of tumor lysis syndrome and prevention of clinical consequences of tumor lysis syndrome are mandatory. The objective of this review is to describe pathophysiological mechanisms, biological and clinical manifestations of tumor Lysis syndrome, and to provide upto-date guidelines to ensure prevention of tumor lysis syndrome. Review of selected studies on tumor lysis syndrome published at the PubMed database www.pubmed.gov during the last 20 years. Additional references were retrieved from the studies initially selected. Tumor lysis syndrome is a frequent and life-threatening complication of the newly diagnosed malignancies. Preventive measures, including hydration, uricolytic agents, eviction of factors predisposing to acute kidney injury and, in the more severe patients, on prophylactic renal replacement therapy, are required to prevent or limit clinical consequences of Tumor lysis syndrome. However optimal timing and modalities of prevention remains unknown and may be modified by the changing spectrum of patients at risk of tumor lysis syndrome. Development and validation of risk based strategies is required to limit the high morbidity and mortality of this complication.

Management and outcomes of acute respiratory distress syndrome patients with and without comorbid conditions

RationaleThe standard of care for patients with acute respiratory distress syndrome (ARDS) has been developed based on studies that usually excluded patients with major comorbidities.ObjectivesTo describe treatments and outcomes according to comorbidities in patients with ARDS admitted to 19 ICUs (1997–2014).MethodsPatients were grouped based on comorbidities. Determinants of day-28 mortality were identified by multivariable Cox analysis stratified on center.Measurements and main resultsAmong 4953 ARDS patients, 2545 (51.4%) had major comorbidities; the proportion with major comorbidities increased after 2008. Hematological malignancy was associated with severe ARDS and rescue therapies for refractory hypoxemia. COPD, HIV infection, and hematological malignancy were associated with a lower likelihood of invasive mechanical ventilation on the admission day. Admission-day SOFA score was higher in patients with major comorbidities, who more often received vasopressors, dialysis, or treatment-limitation decisions. Day-28 mortality was 33.7% overall, 27.2% in patients without major comorbidities, and 31.1% (COPD) to 56% (hematological malignancy) in patients with major comorbidities. By multivariable analysis, mortality was lower in patients with COPD and higher in those with chronic heart failure, solid tumors, or hematological malignancies. Mortality was independently associated with PaO2/FiO2 and PaCO2 on day 1, ARDS of pulmonary origin, worse SOFA score, and ICU-acquired events.ConclusionsHalf the patients with ARDS had major comorbidities, which were associated with severe ARDS, multiple organ dysfunction, and day-28 mortality. These findings do not support the exclusion of ARDS patients with severe comorbidities from randomized clinical trials. Trials in ARDS patients with whatever comorbidities are warranted.

The clinical features of cardiac involvement in patients with severe thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening microangiopathic syndrome [1]. Mortality can reach 20% [1]. A severe deficit in ADAMTS13 (a disintegrin and metalloprotease with thrombospodin type I repeat 13, which cleaves the von Willebrand factor, vWF) results in the accumulation of unfolded high molecular weight multimers that activate the endothelium and aggregate with platelets in the microvessels. Platelet–vWF thrombi cause ischemic organ failure [2]. TTP-related multiorgan dysfunction primarily affects the heart and the brain [1]. Cardiac involvement in TTP is polymorphous. Benhamou et al. described chest pain (25% of patients), ECG changes (12%), and cardiac insufficiency or ischemia (15%) [3]. Importantly, elevated troponin, found in 60% of patients, was associated with mortality [3]. Cardiac involvement has also been associated with early deaths [4] or TTP unresponsiveness [5]. Its incidence in critically ill patients with TTP has never been assessed. To better describe TTP-related cardiac involvement, we conducted a retrospective study including all TTP patients admitted to our ICU. Cardiac involvement included one of the following elements: chest pain, ischemic changes on ECG, troponin level beyond the upper limit of the reference range, new-onset ischemic changes on cardiac echography, cardiogenic shock, or cardiac arrest. Among the 98 patients included [median (IQR) age 43 (32–53), 67% women, 65% non-Caucasian], 6 (6%) patients died. Thrombotic microangiopathy was severe, with deep thrombocytopenia [11,000 × 109/L (7000– 19,000)] and mechanical hemolytic anemia [Hb 7.7 g/ dL (6.2–9.7), free bilirubin concentration at 38.5 μmol/L (21.7–59), and LDH rate at 1743 (1161–3462)]. All patients had undetectable haptoglobin, negative direct antiglobulin test, and detectable schistocyte. At presentation, TTP-associated conditions included autoimmune disease (25%), HIV infection (12%), pregnancy (4%), and cancer or drug 4%. Cardiac involvement was present in 91% (85.3–96.7) of patients, followed by neurologic (78.6%), kidney (51.5%), and digestive signs (33%). The most frequent cardiac sign was elevated troponin level (71 patients) and elevated troponin was the only sign in 20 (20.4%). ECG changes were found in 58 patients, chest pain in 23, cardiogenic shock in 17, and cardiac arrest in 6 (Fig. 1a). Echocardiography was performed in 56 patients and exhibited left ventricular dysfunction in 9 (16.1%), focal hypokinesia in 11 (19.6%), and pericardial effusion in 12 (21.4%). All patients received immediate plasma exchange (PEX) and steroids. Aspirin was given to 88 (89.8%) patients, preventive anticoagulants to 70 (74.5%), curative anticoagulants for deep venous thrombosis to 28 (28.6%),

The challenge of avoiding intubation in immunocompromised patients with acute respiratory failure

ABSTRACT Introduction: A growing number of immunocompromised (IC) patients with acute hypoxemic respiratory failure (ARF) is admitted to the intensive care unit (ICU) worldwide. Areas covered: This review provides an overview of the current knowledge of the ways to prevent intubation in IC patients with ARF. Expert commentary: Striking differences oppose ARF incidence, characteristics, etiologies and management between IC and non-IC patients. Survival benefits have been reported with early admission to ICU in IC patients. Then, while managing hypoxemia and associated organ dysfunction, the identification of the cause of ARF will be guided by a rigorous clinical assessment at the bedside, further assisted by an invasive or noninvasive diagnostic strategy based on clinical probability for each etiology. Finally, the initial respiratory support aims to avoid mechanical ventilation for the many yet recognizing those patients for whom delaying intubation expose them to suboptimal management. We advocate for not using noninvasive ventilation (NIV) in this setting. A proper evaluation of High-flow nasal cannula oxygen (HFNC) is required in IC patients as to demonstrate its superiority compared to standard oxygen therapy. Day-to-day decisions must strive to avoid delayed intubation, and make every effort to identify ARF etiology.

A Rapidly Reversible Cause of Pulmonary Embolism

Lymphoma cell proliferation in the blood vessels of parenchymal organs may result in vessel obstruction and ischaemia. We report the case of a patient who had intravascular lymphoma with predominant pulmonary involvement. A 38-year-old man was referred to the intensive care unit for acute respiratory failure and prolonged fever. Appropriate investigations failed to demonstrate any bacterial, viral, parasitic, or mycobacterial infection. Chest computed tomography ruled out proximal or sub-segmental pulmonary embolism, but the ventilation/perfusion lung scan indicated a high probability of pulmonary embolism. Examination of a skin biopsy established the diagnosis of intravascular lymphoma. Intravascular lymphoma is a rare disease characterised by exclusive or predominant growth of neoplastic cells within the lumina of small blood vessels. Lung involvement is common but rarely at the forefront of the clinical picture. In the case described here, immediate chemotherapy combined with adequate supportive care ensured a full recovery.

ARDS During Neutropenia Recovery

Acute respiratory failure is a major cause of morbidity in cancer patients and the most common organ failure leading to ICU admission in neutropenic patients. In these patients, acute respiratory failure often stems from a combination of factors that may be closely intertwined, such as infection and cardiogenic edema or alveolar hemorrhage. Several lines of evidence point to an association between neutropenia recovery and declining oxygenation with exacerbation of pre-existing pulmonary disease. Overall, the prevalence of acute respiratory failure during neutropenia recovery may be as high as 50% in patients with risk factors. These factors include the occurrence of pneumonia during neutropenia, delayed or prolonged neutropenia, a fast rate of neutrophil recovery, and invasive pulmonary aspergillosis. In addition, several clinical and laboratory findings suggest that granulocyte colony-stimulating factor may exacerbate the clinical manifestations of neutropenia recovery. Here, we review the evidence suggesting that neutropenia recovery may be associated with exacerbation of acute respiratory failure, and we discuss the factors suspected to be associated with respiratory failure during neutropenia recovery.

Managing Critically Ill Cancer Patients: Another Medical Success Story

A few decades have passed since intensive care unit (ICU) beds have been available for critically ill patients with cancer. Although the initial reports showed dismal prognosis, recent data suggest that an increased number of cancer patients benefit from ICU support, with decreased mortality rates. Advances in the management of the underlying malignancies and support of organ dysfunctions have led to survival gains in patients with life-threatening complications from the malignancy itself, as well as infectious and toxic adverse effects related to the oncological treatments. In this review, we will appraise the prognostic factors and discuss the overall perspective related to the management of critically ill patients with cancer. The prognostic significance of certain factors has changed over time. For example, neutropenia or autologous bone marrow transplantation carries less adverse prognostic implication than 2 decades ago. Similarly, because hematologists and oncologists select patients for ICU admission based on the characteristics of the malignancy, the underlying malignancy rarely influences short-term survival after ICU admission. Since the recent data do not clearly support the benefit of ICU support to unselected critically ill allogeneic BMT recipients, more outcome research is needed in this subgroup. Because of the overall increased survival that has been reported in critically ill cancer patients, we outline easy-to-use and evidence-based ICU admission triage criteria that may help avoid depriving life support to cancer patients who can benefit. Lastly, we propose a research agenda to address unanswered questions.