Cardiotoxicity, including heart failure, thromboembolic events, and myocardial ischemia, is a concern for cardiologists and oncologists. The most frequently involved drugs are anthracyclines. We ...report an episode of coronary spasm due to vincristine, a vinca alkaloid, in a 49-year-old man treated for a diffuse undifferentiated carcinoma. The patient suffered recurrent episodes of typical chest pain with ST-elevation in the inferior area. Coronary spasm was confirmed by an angiogram, which showed normal coronary arteries. No recurrence occurred with the medical management. Coronary spasm induced by vincristine is a newly described facet of chemotherapy-related cardiotoxicity.
Noninvasive ventilation (NIV) improves the outcome of acute cardiogenic pulmonary edema (AcPE) and acute exacerbation of chronic obstructive pulmonary disease (aeCOPD) but is not recommended in ...pneumonia. The aim of this study was to assess the appropriateness of the use of NIV in a prehospital setting, where etiological diagnostics rely mainly on clinical examination. This observational multicenter retrospective study included all the patients treated with NIV by three mobile medical emergency teams in 2015. Prehospital diagnoses and hospital diagnoses were extracted from the medical charts. The appropriateness of NIV was determined by matching the hospital diagnosis to the current guidelines. Among the 14,067 patients screened, 172 (1.2%) were treated with NIV. The more frequent prehospital diagnoses were AcPE (
= 102, 59%), acute respiratory failure of undetermined cause (
= 46, 28%) and aeCOPD (
= 17, 10%). An accurate prehospital diagnosis was more frequent for AcPE (83/88, 94%) than for aeCOPD (14/32, 44%;
< 0.01). Only two of the 25 (8%) pneumonia cases were diagnosed during prehospital management. Prehospital NIV was inappropriate for 32 (21%) patients. Patients with inappropriate NIV had a higher rate of in-hospital intubation than patients with appropriate NIV (38% vs. 8%;
< 0.001). This high frequency of inappropriate NIV could be reduced by an improvement in the prehospital detection of aeCOPD and pneumonia.
IMPORTANCE: High-flow nasal oxygen therapy is increasingly used for acute hypoxemic respiratory failure (AHRF). OBJECTIVE: To determine whether high-flow oxygen therapy decreases mortality among ...immunocompromised patients with AHRF compared with standard oxygen therapy. DESIGN, SETTING, AND PARTICIPANTS: The HIGH randomized clinical trial enrolled 776 adult immunocompromised patients with AHRF (Pao2 <60 mm Hg or Spo2 <90% on room air, or tachypnea >30/min or labored breathing or respiratory distress, and need for oxygen ≥6 L/min) at 32 intensive care units (ICUs) in France between May 19, 2016, and December 31, 2017. INTERVENTIONS: Patients were randomized 1:1 to continuous high-flow oxygen therapy (n = 388) or to standard oxygen therapy (n = 388). MAIN OUTCOMES AND MEASURES: The primary outcome was day-28 mortality. Secondary outcomes included intubation and mechanical ventilation by day 28, Pao2:Fio2 ratio over the 3 days after intubation, respiratory rate, ICU and hospital lengths of stay, ICU-acquired infections, and patient comfort and dyspnea. RESULTS: Of 778 randomized patients (median age, 64 IQR, 54-71 years; 259 33.3% women), 776 (99.7%) completed the trial. At randomization, median respiratory rate was 33/min (IQR, 28-39) vs 32 (IQR, 27-38) and Pao2:Fio2 was 136 (IQR, 96-187) vs 128 (IQR, 92-164) in the intervention and control groups, respectively. Median SOFA score was 6 (IQR, 4-8) in both groups. Mortality on day 28 was not significantly different between groups (35.6% vs 36.1%; difference, −0.5% 95% CI, −7.3% to +6.3%; hazard ratio, 0.98 95% CI, 0.77 to 1.24; P = .94). Intubation rate was not significantly different between groups (38.7% vs 43.8%; difference, −5.1% 95% CI, −12.3% to +2.0%). Compared with controls, patients randomized to high-flow oxygen therapy had a higher Pao2:Fio2 (150 vs 119; difference, 19.5 95% CI, 4.4 to 34.6) and lower respiratory rate after 6 hours (25/min vs 26/min; difference, −1.8/min 95% CI, −3.2 to −0.2). No significant difference was observed in ICU length of stay (8 vs 6 days; difference, 0.6 95% CI, −1.0 to +2.2), ICU-acquired infections (10.0% vs 10.6%; difference, −0.6% 95% CI, −4.6 to +4.1), hospital length of stay (24 vs 27 days; difference, −2 days 95% CI, −7.3 to +3.3), or patient comfort and dyspnea scores. CONCLUSIONS AND RELEVANCE: Among critically ill immunocompromised patients with acute respiratory failure, high-flow oxygen therapy did not significantly decrease day-28 mortality compared with standard oxygen therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02739451.
To determine whether the survival gains achieved in critically ill cancer patients in recent years exist in the subset with neutropenia and severe sepsis or septic shock.
Retrospective 11-yr study ...(1998-2008).
Medical intensive care unit in a teaching hospital.
Four hundred twenty-eight intensive care unit patients with cancer, neutropenia, and severe sepsis or septic shock. The primary outcome was hospital mortality.
The main underlying diseases were acute leukemia (35.7%), lymphoma (31.7%), and solid tumors (16.5%). Two hundred thirty-seven (55.5%) patients had microbiologically documented infections, 141 (32.9%) clinically documented infections, and 50 (11.9%) fever of unknown origin. Acute noninfectious conditions were diagnosed in 175 of 428 (41%) patients, including 26 of 50 (52%) patients with fever of unknown origin, 66 of 141 (47%) patients with clinically documented infections, and 83 of 237 (35%) patients with microbiologically documented infections. Early indwelling catheter removal was performed routinely in the 107 (25%) patients without clinical evidence of a septic focus at intensive care unit admission. Early beta-lactam plus aminoglycoside therapy was used in 391 (91.3%) patients. Hospital mortality was 49.8%. Hospital mortality decreased from 58.7% (108 of 184) in 1998-2003 to 43% in 2004-2008 (105 of 244, p = .006). Multivariate analysis identified nine independent predictors of hospital mortality, of which six were associated with higher mortality (older age; need for vasopressors; neurologic, respiratory, or hepatic dysfunction; and acute noninfectious condition) and three with lower mortality (intensive care unit admission after 2003, combination antibiotic therapy including an aminoglycoside, and early indwelling catheter removal).
In neutropenic patients with severe sepsis or septic shock, survival improved over time. Aminoglycoside use and early catheter removal in patients with undocumented sepsis may improve survival. Acute noninfectious conditions are associated with increased mortality, underlining the need for thorough and repeated clinical assessments.
OBJECTIVE:Early identification of causative microorganism(s) in patients with severe infection is crucial to optimize antimicrobial use and patient survival. However, current culture-based pathogen ...identification is slow and unreliable such that broad-spectrum antibiotics are often used to insure coverage of all potential organisms, carrying risks of overtreatment, toxicity, and selection of multidrug-resistant bacteria. We compared the results obtained using a novel, culture-independent polymerase chain reaction/electrospray ionization-mass spectrometry technology with those obtained by standard microbiological testing and evaluated the potential clinical implications of this technique.
DESIGN:Observational study.
SETTING:Nine ICUs in six European countries.
PATIENTS:Patients admitted between October 2013 and June 2014 with suspected or proven bloodstream infection, pneumonia, or sterile fluid and tissue infection were considered for inclusion.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:We tested 616 bloodstream infection, 185 pneumonia, and 110 sterile fluid and tissue specimens from 529 patients. From the 616 bloodstream infection samples, polymerase chain reaction/electrospray ionization-mass spectrometry identified a pathogen in 228 cases (37%) and culture in just 68 (11%). Culture was positive and polymerase chain reaction/electrospray ionization-mass spectrometry negative in 13 cases, and both were negative in 384 cases, giving polymerase chain reaction/electrospray ionization-mass spectrometry a sensitivity of 81%, specificity of 69%, and negative predictive value of 97% at 6 hours from sample acquisition. The distribution of organisms was similar with both techniques. Similar observations were made for pneumonia and sterile fluid and tissue specimens. Independent clinical analysis of results suggested that polymerase chain reaction/electrospray ionization-mass spectrometry technology could potentially have resulted in altered treatment in up to 57% of patients.
CONCLUSIONS:Polymerase chain reaction/electrospray ionization-mass spectrometry provides rapid pathogen identification in critically ill patients. The ability to rule out infection within 6 hours has potential clinical and economic benefits.
Summary Background Generalised convulsive status epilepticus (GCSE) should be treated quickly. Benzodiazepines are the only drug treatment available so far that is effective before admission to ...hospital. We assessed whether addition of the antiepileptic drug levetiracetam to the benzodiazepine clonazepam would improve prehospital treatment of GCSE. Methods We did a prehospital, randomised, double-blind, phase 3, placebo-controlled, superiority trial to determine the efficacy of adding intravenous levetiracetam (2·5 g) to clonazepam (1 mg) in treatment of GCSE in 13 emergency medical service centres and 26 hospital departments in France. Randomisation was done at the Paris Descartes Clinical Research Unit with a list of random numbers generated by computer. Adults with convulsions lasting longer than 5 min were randomly assigned (1:1) by prehospital physicians to receive levetiracetam or placebo in combination with clonazepam. All physicians and paramedics were masked to group assignments. If the status epilepticus lasted beyond 5 min after drug injection, a second dose of 1 mg clonazepam was given. The primary outcome was cessation of convulsions within 15 min of drug injection. We analysed the modified intention-to-treat population that had received at least one injection of clonazepam and levetiracetam or placebo, excluding patients without valid consent and those randomised more than once. The trial is registered at EudraCT, number 2007-005782-35. Findings Between July 20, 2009, and Dec 15, 2012, 107 patients were randomly assigned to receive placebo and 96 were assigned to receive levetiracetam. The trial was discontinued on Dec 15, 2012 when interim analysis showed no evidence of a treatment difference, and 68 patients in each group were included in the modified intention-to-treat analysis. Convulsions stopped at 15 min of drug injection in 57 of 68 patients (84%) receiving clonazepam and placebo and in 50 of 68 patients (74%) receiving clonazepam and levetiracetam (percentage difference −10·3%, 95% CI −24·0 to 3·4). Three deaths, 19 of 47 (40 %) serious adverse events, and 90 of 197 (46%) non-serious events were reported in the levetiracetam group, and four deaths, 28 of 47 (60%) serious events, and 107 of 197 (54%) non-serious events were reported in the placebo group. Interpretation The addition of levetiracetam to clonazepam treatment presented no advantage over clonazepam treatment alone in the control of GCSE before admission to hospital. Future prehospital trials could assess the efficacy of clonazepam alone as a first-line treatment in status epilepticus and the efficacy of a second injection of clonazepam with another antiepileptic drug as second-line treatment. Funding UCB Pharma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
OBJECTIVES:Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. ...We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission.
DESIGN:Retrospective, multicenter, national study over an 18-year period (2000–2017).
SETTING:Thirty-one French ICUs.
PATIENTS:The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were “definite thyroid storm,” as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure.
MEASUREMENTS AND MAIN RESULTS:Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves’ disease represented the main thyroid storm etiologies (30 33% and 24 26% patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients 26%) and antithyroid-drug discontinuation (13 patients 14%) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03–1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77–50.12; p = 0.008) as being independently associated with in-ICU mortality.
CONCLUSIONS:Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.
ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13) deficiency has been reported in patients with sepsis but its clinical relevance and pathophysiology remain ...unclear. Our objectives were to assess the clinical significance, prognostic value and pathophysiology of ADAMTS13 deficiency in patients with septic shock with and without disseminated intravascular coagulation (DIC).
This was a prospective monocenter cohort study of patients with septic shock. Von Willebrand Factor, ADAMTS13-related parameters and plasma IL-6 concentration were measured at inclusion to the study. Patients were categorized into three groups according to the presence of ADAMT13 deficiency (<30%) or DIC.
This study included 72 patients with a median age of 59 years (interquartile range (IQR) 50 to 71). Each of the included patients received vasopressors; 55 (76%) were under mechanical ventilation and 22 (33%) underwent renal replacement therapy. Overall, 19 patients (26%) had DIC, and 36 patients had ADMTS13 deficiency (50%). Patients with DIC, ADAMTS13 deficiency or both were more severe at ICU admission. Mortality was higher in septic shock patients from group one. By multivariate analysis, Simplified Acute Physiology Score 2 (SAPS2) score (odds ratio (OR) 1.11/point; 95% CI 1.01 to 1.24) and ADAMTS13 activity <30% (OR 11.86; 95% CI 1.36 to 103.52) were independently associated with hospital mortality. There was no correlation between ADAMTS13 activity and the International Society for Thrombosis and Haemostasis (ISTH) score (rs = -0.97, P = 0.41) suggesting that ADAMTS13 functional deficiency and DIC were independent parameters. IL-6 level was higher in patients with ADAMTS13 activity <30% 895 (IQR 330 to 1843) pg/mL versus 83 (IQR 43 to 118), P = 0.0003).
Septic shock was associated with a functional deficiency of ADAMTS13, independently of DIC. ADAMTS13 functional deficiency is then a prognostic factor for mortality in septic shock patients, independently of DIC.
Russia's invasion of Ukraine has triggered the biggest conflict in Europe since the Second World War. It has forced countries to prepare for engagement on a massive scale, namely, a high-intensity ...war between nation states. A potential massive influx of wounded personnel risks saturating logistical supply chains and requires changes to not only medical care but also a paradigm shift. In this context, the principle of distributive justice is key. The aim is to save as many lives as possible through triage, which consists in "doing the greatest good for the greatest number." This idea is fundamental, as an emergency that has passed is no longer an emergency. However, international texts and treaties not only underline that the sole criterion for triage is clinical severity, but they also fail to take into account the patient's status (civilian, friend, and foe). In a high-intensity warfare situation, these texts, and the medical-surgical triage criteria they provide are insufficient, as caregivers may be required to make decisions based on the status of the patient. The need to make such choices could cause psychological suffering among military caregivers, as individuals are recurrently faced with difficult ethical dilemmas. One way to prevent this happening is to provide predeployment training in wartime medical ethics. The latter would include both instruction in international humanitarian law and practical simulations of clinical situations where the person is faced with an ethical dilemma.
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