Capillary leak syndrome: State of the art in 2021.

Capillary leak syndrome (CLS) is an increasingly acknowledged multifaceted and potentially lethal disease. Initial nonspecific symptoms are followed by the intriguing CLS hallmark: the double paradox associating diffuse severe edema and hypovolemia, along with hemoconcentration and hypoalbuminemia. Spontaneous resolutive phase is often associated with poor outcome due to iatrogenic fluid overload during leak phase. CLS is mainly triggered by drugs (anti-tumoral therapies), malignancy, infections (mostly viruses) and inflammatory diseases. Its idiopathic form is named after its eponymous finder: Clarkson's disease. CLS pathophysiology involves a severe, transient and multifactorial endothelial disruption which mechanisms are still unclear. Empirical and based-on-experience treatment implies symptomatic care during the acute phase (with the eventual addition of drugs amplifying cAMP levels in the severest cases), and the prophylactic use of monthly polyvalent immunoglobulins to prevent relapses. As CLS literature is scattered, we aimed to collect and summarize the current knowledge on CLS to facilitate its diagnosis, understanding and management.

[Idiopathic systemic capillary leak syndrome: 2 cases with misleading presentation]. / Syndrome de fuite capillaire idiopathique : 2 cas cliniques de présentation trompeuse.

INTRODUCTION: Idiopathic systemic capillary leak syndrome (ISCLS) also known as Clarkson syndrome is a rare and sudden life-threatening entity. Three consecutive phases are described. A first non-specific prodromal phase often manifests as "flu-like" symptoms and precedes capillary leak phase with major hypovolemic and distributive shock leading to serious and frequent multiorgan dysfunction syndrome (MODS). Severe hypovolemia contrasts with edema, and hemoconcentration with hypoalbuminemia. ISCLS is characterized by these two clinical and biological paradoxes. Subsequent recovery phase exhibits organ function restoration along with interstitial/intravascular volumes normalization. The latter occurs spontaneously and systematically in patients surviving from leak phase. OBSERVATIONS: We report here two ISCLS cases admitted in intensive care unit (ICU) both enhancing initial misdiagnosis possibly lowering prognosis and outcome. Our first 28-year-old female patient was admitted for « polycythemia vera ¼ although hemoconcentration was attributable to hypovolemia. She presented circulatory arrest during the second bloodletting session and complicated with MODS. In and out ICU favorable outcome was noted on intravenous immunoglobulin therapy. A second 57-year-old male patient was admitted in ICU for severe "myositis" (myalgia and rhabdomyolysis) although rectified diagnosis retained compartment syndrome (muscular severe edema following capillary leak). Rapid and refractory hypovolemic shock appeared with subsequent MODS leading to death. CONCLUSION: ISCLS pathophysiology remains unknown but certainly implies transitory endothelial dysfunction. Impossibility of randomized controlled trial for this exceptional disease led to based-on-experience therapeutic guidelines implying symptomatic care (cardiac output surveillance, nephroprotection, prudent fluid intake, prudent vasoactive amine use) and specific therapies (intravenous aminophylline during severe flares). Although enhancing controversial and even deleterious effects during the acute phase, polyvalent immunoglobulins are effective for relapse prevention. Syndromic diagnosis is difficult, but its precocious finding constitutes a key-element in better outcome before organ failure.

Sources of interrater variability and prognostic value of standardized EEG features in post-anoxic coma after resuscitated cardiac arrest.

OBJECTIVES: To assess interrater variability and prognostic value of simple EEG features based on the recent American Clinical Neurophysiology Society (ACNS) classification in post cardiac arrest comatose patients. METHODS: All patients admitted for a resuscitated cardiac arrest in a university hospital were prospectively included in the study. EEG interpretation was made by 3 independent neurophysiologists (2 senior and 1 junior) blind to the outcome. Kappa score and prognostic performances were estimated for each EEG pattern and discrepancies were analyzed. RESULTS: 122 cardiac arrest patients were admitted of whom 48 went through a full neurologic evaluation. Eighty-one percent had an unfavorable outcome. Burst suppression, paroxystic seizure activity, and non-reactive EEG were strongly associated with an unfavorable evolution. Kappa score between the senior neurophysiologists was excellent or substantial while it was only fair or slight between the junior and senior neurophysiologists. Reactivity, discontinuity and electrographic seizure were patterns particularly subject to discrepancy. CONCLUSIONS: Bedside EEG is an excellent tool for predicting outcome of post-anoxic coma through simple EEG features. However, the interrater variability emphasizes the need to be well trained for the standardized methods of evaluating EEG parameters. SIGNIFICANCE: A second look at complex patterns seems mandatory. The development of automated tools could help to improve the reliability of EEG interpretation.

Tropheryma whipplei DNA in bronchoalveolar lavage samples: a case control study.

Tropheryma whipplei, the causative bacterium of Whipple's disease, can cause acute pneumonia. We performed a case-control study including patients with T. whipplei in bronchoalveolar lavages (BALs) and controls in order to compare patients' clinical statuses. We tested T. whipplei PCR from January 2013 to December 2014, in all the 1438 BALs in Marseille, France. Controls were hospitalized in the same unit during the same period and were comparable in age and sex. Eighty-eight BALs (6.1%) were positive for T. whipplei and 58 patients had pneumonia. Sixty-four patients were male with a mean age of 50.5 years. T. whipplei was commonly associated with aspiration pneumonia (18/88 patients compared with 6/88 controls, p 0.01) and was detected as a unique pathogen in nine cases. Overall, no difference was observed regarding immunocompromised status. Nevertheless, the six AIDS-infected patients in the T. whipplei group had a significantly lower CD4 level than the five AIDS-infected patients in the control group (49 vs. 320/mm3, p 0.01); in addition, five patients were treated with tumour necrosis factor alpha inhibitors (including three treated by monocolonal antibodies and two with soluble receptor) compared with none of the controls (p 0.03). Pneumocystis jirovecii was frequently associated with the T. whipplei group (7/88 vs. 0/88 in control group), Pseudomonas aeruginosa was only detected in the control group (8/88). This study adds evidence for a causative role of T. whipplei in pneumonia. In the future, an experimental model of pneumonia induced by T. whipplei will prove its role in pneumonia.

[Ischemic heart failure making the diagnosis of a Vaquez disease: a rare event]. / Choc cardiogénique ischémique révélateur d'une maladie de Vaquez, un événement rare.

We present the case of a 46-year-old patient without any past medical history, admitted to our ICU for cardiogenic shock complicating acute coronary syndrome. The blood tests found polycethemia, a polycethemia vera was suspected and confirmed by genetic analysis. Ischemic heart failure as an initial symptom of polycethemia vera and its treatment by arterial bleeding is a rare event that we describe in this article.

Exercise-induced inflammatory reaction affects electromyographic changes in skeletal muscle during dynamic contractions in humans.

In order to assess the role of exercise-induced inflammatory reactions on electromyographic (EMG) changes in humans, we have recorded, during a 3-min dynamic handgrip exercise at a high strength (112 w), the surface EMG and the compound evoked muscle action potential (M-wave) in control conditions, and this after ingestion of a well known cyclooxygenase blocker i.e. acetylsalicylic acid (ASA), either as a single dose treatment (10 mg/kg) and as a 3-day treatment (30 mg/kg per day). The power spectrum density function of EMG allowed us to compute both the median frequency (MF) and the energies in a low- and a high-frequency band. We estimated the lactic acid concentration from blood samples drawn from an antecubital vein and we noted that its production was not affected by ASA (single dose or 3-day treatment). We observed at the end of exercise that no change in M-wave duration and conduction time occurred though the median frequency always fell. However, we noted that the slope of the MF vs. time regression line was halved after the 3-day ASA treatment which may indicate that inflammatory reactions are elicited by exhausting contractions and affect the EMG changes.

Is ventilator-associated pneumonia an independent risk factor for death?

BACKGROUND: Ventilator-associated pneumonia (VAP) has been implicitly accused of increasing mortality. However, it is not certain that pneumonia is responsible for death or whether fatal outcome is caused by other risk factors for death that exist before the onset of pneumonia. The aim of this study was to evaluate the attributable mortality caused by VAP by performing a matched-paired, case-control study between patients who died and patients who were discharged from the intensive care unit after more than 48 h of mechanical ventilation. METHODS: During the study period, 135 consecutive deaths were included in the case group. Case-control matching criteria were as follows: (1) diagnosis on admission that corresponded to 1 of 11 predefined diagnostic groups; (2) age difference within 10 yr; (3) sex; (4) admission within 1 yr; (5) APACHE II score within 7 points; (6) ventilation of control patients for at least as long as the cases. Precise clinical, radiologic, and microbiologic definitions were used to identify VAP. RESULTS: Analysis was performed on 108 pairs that were matched with 91% of success. There were 39 patients (36.1%) who developed VAP in each group. Multivariate analysis showed that renal failure, bone marrow failure, and treatment with corticosteroids but not VAP were independent risk factors for death. There was no difference observed between cases and controls concerning the clinical and microbiologic diagnostic criteria for pneumonia. CONCLUSION: Ventilator-associated pneumonia does not appear to be an independent risk factor for death.

High or low doses of almitrine bismesylate in ARDS patients responding to inhaled NO and receiving norepinephrine?

OBJECTIVE: To evaluate the effects on oxygenation and pulmonary haemodynamics of almitrine bismesylate (AB) 5 microg/kg per minute and 16 microg/kg per minute in ARDS patients responding to and receiving inhaled NO (iNO) and presenting septic shock requiring norepinephrine, while no difference was observed in a previous trial including iNO responders and nonresponders. DESIGN: Prospective, cohort study. SETTING: Adult medico-surgical intensive care unit of a university hospital. PATIENTS: Fifteen patients with ARDS receiving and responding to iNO (10 ppm) and presenting septic shock requiring norepinephrine (mean 0.5+/-0.45 microg/kg per minute, range 0.08- 2.08). INTERVENTIONS: The protocol consisted of two consecutive phases in a fixed order: continuous intravenous infusion of AB 5 microg/kg per minute for 30 min, and continuous intravenous infusion of AB 16 microg/kg per minute for 30 min. MEASUREMENTS AND MAIN RESULTS: AB 5 microg/kg per minute significantly increased PaO2/FiO2 ( P<0.05) compared with iNO alone [160 (range 77-450) mmHg vs 122 (range 70-225) mmHg]. AB 16 microg/kg per minute produced a greater increase of PaO2/FiO2 ( P<0.05) when compared with 5 microg/kg per minute [227 (range 84-501) mmHg]. AB did not improve shunt at any dose regimen. AB produced an increase in mean pulmonary arterial pressure (MPAP) from 22+/-5 to 25+/-4 mmHg ( P<0.03). MPAP did not significantly increase between the two doses. Pulmonary vascular resistances and other haemodynamic and respiratory parameters were not affected by almitrine bismesylate. CONCLUSIONS: These results suggest that it is possible to obtain a further improvement in oxygenation by increasing AB infusion rate in ARDS patients iNO responders receiving norepinephrine. Due to the potential deleterious effects of AB, this strategy should be used in the most severely hypoxaemic patients.

Use of heliox in patients with severe exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To assess whether patients with chronic obstructive pulmonary disease treated with heliox have a better prognosis than those treated with standard therapy. DESIGN: Retrospective analysis over 18 months. SETTING: Academic emergency department. PATIENTS: Eighty-one patients admitted with exacerbation of chronic obstructive pulmonary disease and respiratory acidosis. INTERVENTIONS: Use of helium-oxygen mixture as an adjunctive therapy. MEASUREMENTS AND MAIN RESULTS: The following data were collected: age, gender, medical history, vital signs, arterial blood gas at admission, emergency room treatment, requirement for intubation, admission in intensive care unit, length of stay, and evolution. Patients were classified into two groups according to whether heliox was used as a therapeutic agent (heliox group) or not (standard group). Chi-square test and Student's t-test were used for statistical analysis (significant at p <.05). In both groups, the following data were similar: age, gender, medical history, vital signs, initial arterial blood gas, and emergency room treatment. Significant decreases in intubation, and mortality rate were identified in the heliox group. Significant decreases in intensive care unit stay and in-hospital stay were observed for survivors in the heliox group. CONCLUSION: Use of heliox seems to improve prognosis in patients with severe acute exacerbation of chronic obstructive pulmonary disease. Prospective randomized studies are needed to confirm these results.

[Severe air embolism after surgical irrigation with hydrogen peroxide]. / Embolie gazeuse grave après une irrigation chirurgicale à l'eau oxygénée.

BACKGROUND: Hydrogen peroxide is widely used for its antiseptic properties. In certain circumstances, however the risk of air embolism can create a life-threatening situation. CASE REPORT: A 16-year-old adolescent required surgical treatment for femorotibial trauma. During the surgical procedure, cardiac arrest suddenly occurred when hydrogen peroxide was being used to irrigate the wound. A central catheter was inserted and aspiration of air bubbles in the line led to the diagnosis of air embolism. Outcome was unfavorable despite successful resuscitation. A chronic neurovegatative state ensued and the patient died 8 months later. DISCUSSION: Several cases of air embolism have been described due to hydrogen peroxide in surgical, medical and accidental circumstances. Our case emphasizes the potential danger of using hydrogen peroxide in certain situations, including orthopedic surgery. Clinicians should be aware that hydrogen peroxide is not a perfectly safe product.

[Fat embolism after intrapenile injection of sweet almond oil]. / Embolie graisseuse après injection intrapénienne d'huile d'amande douce.

We report a case of fat embolism following self injection of vegetable oil in the penis, to treat an impotence. The patient developed respiratory failure and neurological disorders as confusion. A chest roentgenogram revealed diffuse alveolar infiltrate. Initially, he presented an hemoconcentration, and fat globules in his urine. The outcome was favourable in 72 hours, with oxygen and hydration. The diagnosis of fat embolism was made after neurological improvement: the patient admitted to injection his penis with vegetable oil, in his corpus cavernosum.

Respective and combined effects of prone position and inhaled nitric oxide in patients with acute respiratory distress syndrome.

Inhaled nitric oxide (NO) and prone position (PP) are two of the new therapeutics proposed in the setting of acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the hemodynamic and respiratory effects of NO and prone position in patients with ARDS. Fourteen patients, sedated, paralyzed, and ventilated using volume-control mode, were prospectively investigated. All patients had a radial artery catheter, a pulmonary artery catheter, and a 3-F fiberoptic thermistor catheter advanced via the femoral artery into the descending aorta. The protocol consisted of seven phases: baseline measurements in supine position, SP (T0); SP + NO (T1); baseline 2 in SP (T2); PP without NO (T3); NO + PP (T4); SP + NO (T5); and PP + NO (T6). Inhaled NO (T1) induced an increase in PO2/FI(O2) (from 128 +/- 44 to 180 +/- 75 mm Hg, p < 0.004). Prone position (T3) resulted in an increase in PO2/FI(O2) (193 +/- 83 mm Hg, p < 0.003 versus T0). The association of NO with PP (T4) resulted in a significant improvement in PO2/FI(O2) (261 +/- 98 mm Hg) when compared with T0, T1, and T3. Analysis of variance showed a significant and additive effect of NO and PP on both PO2/FI(O2) (p < 0.000) and shunt fraction (QS/QT) (p < 0.01). Since the association of NO with PP presents additive effects on oxygenation, this association can be proposed for the treatment of ARDS.

Left-sided superior vena cava: diagnosis by magnetic resonance imaging.

We describe a case of left-sided superior vena cava. The diagnosis was suggested by chest radiograph after central venous catheter placement. This was subsequently confirmed by magnetic resonance imaging.

[Economic impact of a prescription protocol in an intensive care unit]. / Impact économique d'un protocole de prescription en réanimation.

OBJECTIVE: To assess the economic impact of a prescribing protocol for i.v. fluid therapy and artificial nutrition. STUDY DESIGN: Comparative study, before and during use of the protocol. PATIENTS: The study included 555 ICU patients allocated into two groups, before and after starting with the protocol. The groups were comparable for number, pathologies, age, severity score, duration of ICU stay, incidence of nosocomial infections, mortality rate. METHOD: In February 1995, a written literature-based prescribing protocol for fluid therapy (hydroxyethylstarch and albumin), and artificial nutrition (enteral nutrition as first-line therapy) was devised. A cost analysis was made for two 6-month periods: before (August 1994 to January 1995) and after start of protocol (February to July 1995). RESULTS: The prescription of albumin and hydroxyethylstarch decreased (by 33 and 58% respectively), whereas administration of Ringer lactate and gelatine solutes increased simultaneously. This induced a cost saving of 15,000 FF (a 20% decrease in cost). The reduction of parenteral nutrition in favour of early enteral nutrition induced a cost saving of 56,000 FF (31% decrease in cost). CONCLUSION: Our prescribing protocol generated a cost saving of 9% of the pharmaceutical budget and decreased the cost-benefit ratio of our ICU.

Fatal pneumonia due to Serratia proteamaculans subsp. quinovora.

Serratia proteamaculans subsp. quinovora was isolated from several samples (blood cultures, tracheal aspirates, pleural effusion) from a patient with pneumonia. This is the first clinical isolate and the first documented human infection caused by this organism.

Serratia fonticola isolated from a leg abscess.

Serratia fonticola was isolated from a very large leg abscess in a patient following an accident. This is the first documented human infection due to S. fonticola.