Biomarkers for Early Diagnosis of Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

Many biomarkers have been proposed for the diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH) in adults, but comparative studies are lacking. We analyzed ferritin, glycosylated ferritin, soluble CD25, CD163 and CD14, IL-6, IFN-γ, IL-18, IL-10, IL-1ß, IL-12p70, IL-17α, IP-10, and CXCL9 levels to differentiate HLH from sepsis in critically ill patients. Of 120 patients, HLH was confirmed for 14 patients. Among the biomarkers tested, ferritin, IL-18, and glycosylated ferritin were the most efficient parameters for early diagnosis of HLH. With a sensitivity set at 85%, ferritin, IL-18, and glycosylated ferritin were the biomarkers with the highest specificity: 84, 79, and 71% respectively. Combining IL-18 with the HScore provided a new score with an increased specificity compared to the HScore alone, 86% compared to 70% with a sensitivity set at 100%. A distinct cytokine pattern was highlighted in patients with malignancy-triggered HLH, with highly increased levels of INF-É£ and CXCL9, compared to HLH secondary to infection. This is the largest study available to date, comparing diagnostic biomarkers for HLH on a cohort of critically ill adult patients. Serum ferritin was the most discriminating parameter for early diagnosis of secondary HLH. IL18*HScore was identified as a highly potential score.

An ectopic Cushing's syndrome as a cause of severe refractory hypokalemia in the ICU.

Background: Ectopic Cushing's syndrome is a very rare condition caused by an ACTH-secreting tumor outside the pituitary or adrenal glands, and the majority of these cases are encountered in the context of paraneoplastic syndromes. The ectopic source of ACTH secretion is not always obvious to detection and can be challenging. We report a rare case, in which a hidden ACTH-secreting carcinoid tumor of the lung caused a severe refractory hypokalemia, leading us to a race against time to locate the tumor.Case presentation: A 33-year-old young male was admitted to the ICU for the management of a severe hypokalemia, and complains from several months of depression, increased weight, disabling non-radiating dorsal lower back pain and refractory arterial hypertension. The physical examination immediately suggested a Cushing's syndrome. The 24-h cortisoluria confirmed hypercortisolism and the increased ACTH level was oriented towards ACTH-dependent Cushing's syndrome. Thereafter, a dexamethasone suppression test was negative, indicating in favor of ectopic ACTH secretion. The etiological assessment via imaging and isotopes revealed a solitary pulmonary nodule at the right lower lobe estimated at 18 mm, the resection and anatomopathological analysis of which led to the diagnosis of carcinoid pulmonary tumor, and resolved hypercortisolism and its complications.Conclusion: A delayed diagnosis of Cushing's syndrome result in a consequent morbi-mortality, mainly due to cardiovascular events. The optimal treatment for ectopic Cushing's syndrome is surgical resection, thus making the localization of the tumor a key element.

Angiotensin converting enzyme inhibitor intoxication: Naloxone to the rescue? Naloxone for ACE inhibitor intoxication.

We report here the case of a patient with perindopril intoxication inducing severe bradycardia together with a profound hypotension. Initiation of a naloxone infusion completely resolved those symptoms. As a consequence, we could recommend as a first step the use of naloxone in order to prevent the use of more invasive therapeutic tools.

Cerebral perfusion alterations and cognitive decline in critically ill sepsis survivors.

INTRODUCTION: We investigated the association between cerebral perfusion perturbations in sepsis with possible cognitive decline (CD) after patients' discharge from the intensive care unit (ICU). METHODS: We studied 28 patients with sepsis and Lawton's Instrumental Activities of Daily Living scale (IADL) scores ≥5 who were discharged from a university ICU institution. We evaluated cerebral circulatory parameters (pulsatility index (PI) and cerebral blood flow index (CBFi) was calculated based on the measured velocity of the middle cerebral artery. Use of the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) test was performed daily, and either the Mini Mental State Examination test (MMSE) or Clock Drawing test was performed at ICU discharge. CD was categorized as persistent coma, positive CAM-ICU test at discharge, MMSE <24, or an abnormal Clock test. RESULTS: Patients had a median pre-ICU IADL score of 6.3 (95% CI 5.9-6.7). Fourteen patients (50%) had CD at discharge. Two were in persistent coma despite sepsis resolution. Information recall was the most affected mental function of the other 12 patients. Only on the first day, patients with CD had higher PI and lower CBFi compared to those without CD (2.2 ± 0.7 vs. 1.4 ± 0.5, p = 0.02; 363 ± 170 vs. 499 ± 133, p = 0.03, respectively). Multivariable analysis revealed delirium, but not PI, as an independent prognostic factor for CD (OR: 29.62, 95%CI 1.91-458.01, p = 0.01). CONCLUSION: Delirium, but not cerebral perfusion alterations, is an independent risk factor for cognitive impairment in septic patients who were discharged from the ICU.

Injection of agitated saline to detect recirculation with transthoracic echocardiography during venovenous extracorporeal oxygenation: A pilot study.

PURPOSE: We assessed the security and efficiency of intravenously injected agitated saline in conjunction with transthoracic echocardiography to identify recirculation in patients supported with a venovenous extracorporeal membrane oxygenation (VV ECMO) device. MATERIALS AND METHODS: We injected agitated saline 4 consecutive times separated by an interval of 5 minutes in 2 patients supported by VV ECMO. In both patients, the drainage cannula was placed in the left femoral vein, and the return cannula was placed in the right internal jugular vein. Echocardiography was performed during the injection and until the bubbles disappeared. The security of the method was assessed by evaluating the mechanical function of the ECMO and the efficiency of the oxygenator. The value of this method was assessed by visualizing the increase of inferior vena cava's echogenicity as well as by measuring the time required for this change to occur after the injection of agitated saline at different ECMO output levels. RESULTS: We did not observe any change in ECMO, oxygenation function, or the hemodynamic status of patients after the 4 injections of agitated saline. The echogenicity of the inferior vena cava increased more rapidly as the ECMO's output increased. The recirculation phenomenon was noted even with low levels of ECMO output (<2 L/min). CONCLUSIONS: Transthoracic echocardiography in conjunction with agitated saline administration may be a safe and easily applicable method to evaluate a recirculation phenomenon in patients supported with VV ECMO.

Transcranial Doppler to assess sepsis-associated encephalopathy in critically ill patients.

BACKGROUND: Transcranial Doppler can detect cerebral perfusion alteration in septic patients. We correlate static Transcranial Doppler findings with clinical signs of sepsis-associated encephalopathy. METHODS: Forty septic patients were examined with Transcranial Doppler on the first and third day of sepsis diagnosis. The pulsatility index (PI) and cerebral blood flow index (CBFi) were calculated by blood velocity in the middle cerebral artery (cm/sec). Patients underwent a daily cognitive assessment with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) test. RESULTS: Twenty-one patients (55%) were found to present confusion. The majority of the patients presented a PI > 1.1 (76%). PI on the first day (but not the third day) could predict a positive CAM-ICU test in septic patients (PI cut-off: 1.3, AUC: 0.905, p < 0.01, sensitivity: 95%, specificity: 88%, AUC: 0.618, p = 0.24). Multivariable analysis showed that PI on the first day is related to a positive CAM-ICU test independent of age and APACHE II score (OR: 5.6, 95% CI: 1.1-29, p = 0.03). A decrease of the PI on the third day was observed in the group that presented initially high PI (>1.3) (2.2 ± 0.71 vs. 1.81 ± 0.64; p = 0.02). On the other hand, an increase in PI was observed in the other patients (1.01 ± 0.15 vs. 1.58 ± 0.57; p < 0.01). On only the first day, the mean blood velocity in the middle cerebral artery and CBFi were found to be lower in those patients with a high initial PI (36 ± 21 vs. 62 ± 28 cm/sec; p < 0.01, 328 ± 101 vs. 581 ± 108; p < 0.01, respectively). CONCLUSIONS: Cerebral perfusion disturbance observed with Transcranial Doppler could explain clinical symptoms of sepsis-associated encephalopathy.

Torsade de pointes in Kearns-Sayre syndrome.

A 47-year-old woman with Kearns-Sayre syndrome (KSS) and an implanted pacemaker for complete heart block was admitted to the intensive care unit following a cardiac arrest due to ventricular tachycardia (torsade de pointes) in the setting of QT prolongation. Complete heart blocks and ventricular tachycardia are implicated as mechanisms of sudden deaths in KSS; such patients may require pacemaker implantation and implantation of an automatic implantable cardioverter-defibrillator.

Is there a correlation between circulating levels of citrulline and intestinal dysfunction in the critically ill?

OBJECTIVE: The aim of this study was to assess the correlation between plasma citrulline and Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, survival, inflammation (C-reactive protein [CRP]), inotrope use, serum levels of prealbumin and albumin, and renal failure in the critically ill patient. METHODS: This prospective observational single-center controlled study included 91 adult patients over a 2-year period. Inclusion criteria were patients staying in the intensive care unit for >48 hours. Patients' renal status was categorized as those with a glomerular filtration rate (GFR) >60 mL/min without renal support, a GFR >60 mL/min with renal support, a GFR <60 mL/min without renal support, and a GFR <60 mL/min with renal support. Plasma citrulline concentrations were categorized into 3 groups: low (0-15 µmol/L), medium (16-35 µmol/L), and high (>36 µmol/L). The relationship between the recorded parameters and these different cut-off values of plasma citrulline concentrations was analyzed. RESULTS: Ninety-one patients (34% female and 66% male) with a mean (SD) age of 69.3 (11.9) years, a mean (SD) body mass index of 24.8 (5.34) kg/m(2), a mean (SD) APACHE II score of 22.4 (7.92), a mean (SD) SOFA score of 8 (4.4), and a mean (SD) plasma citrulline of 21.7 (13.1) µmol/L were enrolled. Only patients with intestinal dysfunction had low plasma citrulline level <15 µmol/L (P = .014). No correlations between serum levels of CRP, albumin, or prealbumin; renal failure; inotrope use; SOFA score; and APACHE II score were found with plasma citrulline level. CONCLUSION: Low plasma citrulline levels in patients correlate well with intestinal dysfunction.

Successful treatment of Chlamydophila pneumoniae acute respiratory distress syndrome with extracorporeal membrane oxygenator: a case report and diagnostic review.

INTRODUCTION: Chlamydophila pneumoniae is a respiratory pathogen known to infect the upper and lower respiratory tracts. Infection severity can range from sub-clinical pulmonary infection to acute respiratory distress syndrome. CASE PRESENTATION: A previously healthy 62-year-old Caucasian man was admitted to our hospital for acute respiratory failure. Serum samples obtained every week starting from the day of admission showed clear-cut seroconversion for C. pneumoniae antibodies. All other cultures obtained during the first days of hospitalization were negative. Despite maximal ventilatory support (high positive end expiratory pressure, fraction of inspired oxygen of 1.0, nitric oxide inhalation, neuromuscular blocking agents and prone positioning), our patient remained severely hypoxemic, which led us to initiate an extracorporeal membrane oxygenation treatment. Extracorporeal membrane oxygenation and hemodiafiltration were withdrawn on day 12. Our patient was extubated on day 18 and discharged from our Intensive Care Unit on day 20. He went home a month later. CONCLUSION: We describe the first published case of acute respiratory distress syndrome due to C. pneumoniae infection successfully treated by extracorporeal membrane oxygenation, a very useful tool in this syndrome. A quick and specific method for the definite diagnosis of Chlamydophila infection should be developed.

Influence of bedside blood insulin measurement on acute coronary syndrome pathways.

BACKGROUND: The aim of the study was to evaluate the influence of blood insulin measurements on acute coronary syndrome (ACS) pathways. METHODS: All patients admitted to the emergency department within 12 months for acute, retrosternal, constrictive chest pain lasting for more than 30 minutes; cardiogenic pulmonary edema; electrocardiogram ST changes; and echographic alterations were included. The study parameters were clinical (age, sex, blood pressure, presence of pulmonary rales and gallop), including classic laboratory tests associated with troponin T, blood insulin levels, and hemoglobin A1C, and echographic values. These were taken on admission and throughout hospital stay. All patients underwent a coronary angiography for ACS diagnosis confirmation as well as treatment intention. RESULTS: Sixty patients were included in the study. Abnormal blood insulin levels were present on admission in 47% of the population. Blood insulin level was significantly correlated to thrombolysis in myocardial infarction coronary perfusion score (Spearman Rank, 0.55, P < 0.0001). Abnormal insulinemia was normalized with reperfusion. Insulin was administered essentially to the 16 patients with hypoinsulinemia. Patients with hypoinsulinemia seem to have the most severe coronary lesions and highest Killip score. CONCLUSIONS: In ACS, insulin levels are altered in half of the patients. After the investigators noted its tight correlation with the thrombolysis in myocardial infarction coronary flow score, its determination could be important in ACS for triggering emergency coronary angiography for percutaneous coronary intervention. This could modify the critical pathways of ACS patients in the emergency department.

Late onset of Aspergillus aortitis presenting as femoral artery embolism following coronary artery bypass graft surgery.

Aspergillus sp. are ubiquitous mould infections and in most patients, the source is presumed to be air-borne infections during surgical procedures. Prevention of these infections requires special attention of ventilation systems in operating rooms. Post-operative aspergillosis occurs mainly in immunocompromised patients as well as those who receive corticosteroids temporarily. We report a case of a 71-year-old immunocompromised patient who developed multiple lower limb embolisms due to Aspergillus niger originating from an aortitis of the ascending aorta nine months following coronary artery bypass graft (CABG) surgery.

Comparison of dopamine and norepinephrine in the treatment of shock.

BACKGROUND: Both dopamine and norepinephrine are recommended as first-line vasopressor agents in the treatment of shock. There is a continuing controversy about whether one agent is superior to the other. METHODS: In this multicenter, randomized trial, we assigned patients with shock to receive either dopamine or norepinephrine as first-line vasopressor therapy to restore and maintain blood pressure. When blood pressure could not be maintained with a dose of 20 microg per kilogram of body weight per minute for dopamine or a dose of 0.19 microg per kilogram per minute for norepinephrine, open-label norepinephrine, epinephrine, or vasopressin could be added. The primary outcome was the rate of death at 28 days after randomization; secondary end points included the number of days without need for organ support and the occurrence of adverse events. RESULTS: The trial included 1679 patients, of whom 858 were assigned to dopamine and 821 to norepinephrine. The baseline characteristics of the groups were similar. There was no significant between-group difference in the rate of death at 28 days (52.5% in the dopamine group and 48.5% in the norepinephrine group; odds ratio with dopamine, 1.17; 95% confidence interval, 0.97 to 1.42; P=0.10). However, there were more arrhythmic events among the patients treated with dopamine than among those treated with norepinephrine (207 events [24.1%] vs. 102 events [12.4%], P<0.001). A subgroup analysis showed that dopamine, as compared with norepinephrine, was associated with an increased rate of death at 28 days among the 280 patients with cardiogenic shock but not among the 1044 patients with septic shock or the 263 with hypovolemic shock (P=0.03 for cardiogenic shock, P=0.19 for septic shock, and P=0.84 for hypovolemic shock, in Kaplan-Meier analyses). CONCLUSIONS: Although there was no significant difference in the rate of death between patients with shock who were treated with dopamine as the first-line vasopressor agent and those who were treated with norepinephrine, the use of dopamine was associated with a greater number of adverse events. (ClinicalTrials.gov number, NCT00314704.)

Upper gastrointestinal bleeding related to emphysematous cholecystitis due to Clostridium perfringens.

We describe the case of a 46-year-old man admitted for upper gastrointestinal bleeding in the context of cirrhosis. A deep bleeding duodenal ulcer was treated by sclerotherapy. Abdominal pain and fever lead us to perform an abdominal computed tomography, which demonstrated emphysematous cholecystitis. An emergency cholecystectomy was performed and antimicrobial therapy initiated. The patient recovered uneventfully. Links between ulcers and emphysematous cholecystitis are discussed.

Ease of using a dedicated percutaneous closure device after inadvertent cannulation of the subclavian artery: case report.

Inadvertent puncture of the subclavian artery is a relatively frequent and potentially disastrous complication of attempted central venous access. Due to its noncompressible location, accidental subclavian arterial cannulation may result in hemorrhage as the sheath is removed. We report a new case of successful percutaneous closure of the subclavian artery which had been inadvertently cannulated, using a closure device based on a collagen plug (Angio-Seal, St. Jude Medical). This was performed in a patient who had received maximal antiplatelet and anticoagulation therapies because of prior coronary stenting in the context of cardiogenic shock. There was no prior angiographic assessment, as arterial puncture was presumed to have been distal to the right common artery and vertebral arteries. No complications were observed in this high-risk patient, suggesting that this technique could be used once the procedure has been evaluated prospectively.

Drotrecogin alfa (activated) for severe sepsis: could we consider a shorter treatment period in patients with a favorable course?

PURPOSE: The objective of this study was to develop a model to identify patients in whom drotrecogin alfa (activated) (DAA) might be administered for periods shorter than the recommended 96 hours. METHODS: We did a retrospective chart review of all 124 patients treated with a standard 96-hour infusion of DAA in a 31-bed department of intensive care. Using a stepwise approach, we identified and combined parameters that could help predict outcomes to achieve the best sensitivity associated with 100% specificity. RESULTS: Twenty-one (17%) of the 124 patients had a favorable outcome (left the intensive care unit within 5 days of DAA initiation); of these, 11 had an increase in arterial pH in the first 24 hours of treatment compared with 22 (21%) of the 103 patients with intermediate (intensive care unit stay >5 days after DAA initiation) or unfavorable (died within 5 days of DAA initiation) outcomes (P = not significant). Eight (72.7%) of these 11 patients and no other patient showed a decrease in sequential organ failure assessment score of at least 50% during the first 24 hours (P < .001). By combining these 2 variables, we could identify, with 100% specificity, 8 of the patients with a favorable outcome (38%) who made a prompt recovery. CONCLUSIONS: A simple model based on sequential organ failure assessment score and arterial pH can help identify patients with a rapid favorable course in whom a shorter duration of DAA treatment may be justified.