Gilles Bernardin

Estimating cardiac filling pressure in mechanically ventilated patients with hyperinflation

ObjectiveWhen positive end-expiratory pressure (PEEP) is applied, the intracavitary left ventricular end-diastolic pressure (LVEDP) exceeds the LV filling pressure because pericardial pressure exceeds 0 at end-expiration. Under those conditions, the LV filling pressure is itself better reflected by the transmural LVEDP (tLVEDP) (LVEDP minus pericardial pressure). By extension, end-expiratory pulmonary artery occlusion pressure (eePAOP), as an estimate of end-expiratory LVEDP, overestimates LV filling pressure when pericardial pressure is >0, because it occurs when PEEP is present. We hypothesized that LV filling pressure could be measured from eePAOP by also knowing the proportional transmission of alveolar pressure to pulmonary vessels calculated as index of transmission = (end-inspiratory PAOP − eePAOP)/(plateau pressure − total PEEP). We calculated transmural pulmonary artery occlusion pressure (tPAOP) with this equation: tPAOP = eePAOP − (index of transmission × total PEEP). We compared tPAOP with airway disconnection nadir PAOP measured during rapid airway disconnection in subjects undergoing PEEP with and without evidence of dynamic pulmonary hyperinflation. DesignProspective study. SettingMedical intensive care unit of a university hospital. PatientsWe studied 107 patients mechanically ventilated with PEEP for acute respiratory failure. Patients without dynamic pulmonary hyperinflation (group A; n = 58) were analyzed separately from patients with dynamic pulmonary hyperinflation (group B; n = 49). InterventionTransient airway disconnection. Measurements and Main ResultsIn group A, tPAOP (8.5 ± 6.0 mm Hg) and nadir PAOP (8.6 ± 6.0 mm Hg) did not differ from each other but were lower than eePAOP (12.4 ± 5.6 mm Hg;p < .05). The agreement between tPAOP and nadir PAOP was good (bias, 0.15 mm Hg; limits of agreement, −1.5–1.8 mm Hg). In group B, tPAOP (9.7 ± 5.4 mm Hg) was lower than both nadir PAOP and eePAOP (12.1 ± 5.4 and 13.9 ± 5.2 mm Hg, respectively;p < .05 for both comparisons). The agreement between tPAOP and nadir PAOP was poor (bias, 2.3 mm Hg; limits of agreement, −0.2–4.8 mm Hg). ConclusionsIndexing the transmission of proportional alveolar pressure to PAOP in the estimation of LV filling pressure is equivalent to the nadir method in patients without dynamic pulmonary hyperinflation and may be more reliable than the nadir PAOP method in patients with dynamic pulmonary hyperinflation.

β-adrenergic receptor-dependent and -independent stimulation of adenylate cyclase is impaired during severe sepsis in humans

Objectives: a) To investigate the functional consequences of sepsis on the β-adrenergic signal transduction in human circulating lymphocytes; b) to appreciate sepsis-associated catecholamine and cytokine release. Design: Experimental, comparative study. Setting: Research laboratory in a university hospital. Subjects: Healthy controls (n = 10); critically ill patients who were not septic (n = 7); septic patients with severe sepsis or septic shock (n = 11). Measurements and main results: Experiments were carried out using freshly isolated peripheral blood mononuclear cells (PBMC). We measured β-adrenergic receptor (βAR) number and affinity, and intracellular cAMP content at baseline and after the pharmacological stimulation of each component of the β -adrenergic complex: βAR with isoproterenol, Gs-protein with sodium fluoride (NaF), adenylate cyclase with forskolin. Catecholamine (adrenaline, noradrenaline) and cytokine (TNFα, IL-1α, IL-1β, IL-6) serum levels were measured. In both septic and non-septic patients we observed a similar 40 % down-regulation of βARs compared to controls, and a reduced basal and isoproterenol-stimulated cAMP accumulation (p < 0.05). The cAMP production elicited by NaF or forskolin was lower in septic patients than in the controls (p < 0.01). Forskolin-stimulated cAMP accumulation was significantly lower in septic patients than it was in non-septic ones (p < 0.001). Catecholamine serum concentrations were increased in the two patient groups without any significant difference. Elevated cytokine serum levels were detected in 45 % of the septic patients (versus 14 % of non-septic patients p < 0.05). Conclusions: Patients presenting with severe sepsis or septic shock have extended postreceptor defects of the β-adrenergic signal transduction. This finding suggests a heterologous desensitization of adenylate cyclase stimulation.

Complex partial status epilepticus revealing anti-NMDA receptor encephalitis

Encephalitis with anti-NMDA receptor antibodies is a recently-recognised form of paraneoplastic encephalitis characterized by a prodromal phase of unspecific illness with fever resembling viral disease, followed by memory loss, psychiatric features, seizures, disturbed consciousness, prominent abnormal movements and autonomic imbalance. Association with ovarian teratoma is common. Neurological outcome can be good, especially when surgery is performed at an early stage. Here, we report a case of anti-NMDA receptor encephalitis associated with ovarian teratoma presenting with inaugural complex partial status epilepticus. The nature of abnormal movements at early stages was unclear and abnormal movements were misinterpreted as the recurrence of partial epileptic seizures. Despite its rarity, all clinicians treating epilepsy and movement disorders should be familiar with anti-NMDA receptor encephalitis, that appears to be a very severe but curable disease.

Transthoracic Echocardiography with Doppler Tissue Imaging predicts weaning failure from mechanical ventilation: evolution of the left ventricle relaxation rate during a spontaneous breathing trial is the key factor in weaning outcome.

IntroductionThere is growing evidence to suggest that transthoracic echocardiography (TTE) should be used to identify the cardiac origin of respiratory weaning failure. The aims of our study were: first, to evaluate the ability of transthoracic echocardiography, with mitral Doppler inflow E velocity to annular tissue Doppler Ea wave velocity (E/Ea) ratio measurement, to predict weaning failure from mechanical ventilation in patients, including those with atrial fibrillation; and second, to determine whether the depressed left ejection fraction and/or diastolic dysfunction participate in weaning outcome.MethodsThe sample included patients on mechanical ventilation for over 48 hours. A complete echocardiography was performed just before the spontaneous breathing trial (SBT) and 10 minutes after starting the SBT. Systolic dysfunction was defined by a left ventricle ejection fraction under 50% and relaxation impairment by a protodiastolic annulus mitral velocity Ea under or equal to 8 cm/second.ResultsA total of 68 patients were included. Twenty failed the weaning process and the other 48 patients succeeded. Before the SBT, the E/Ea ratio was higher in the failed group than in the successful group. The E/Ea measured during the SBT was also higher in the failed group. The cut-off value, obtained from receiver operating characteristics (ROC) curve analysis, to predict weaning failure gave an E/Ea ratio during the SBT of 14.5 with a sensitivity of 75% and a specificity of 95.8%. The left ventricular ejection fraction did not differ between the two groups whereas Ea was lower in the failed group. Ea increased during SBT in the successful group while no change occurred in the failed group.ConclusionsMeasurement of the E/Ea ratio with TTE could predict weaning failure. Diastolic dysfunction with relaxation impairment is strongly associated with weaning failure. Moreover, the impossibility of enhancing the left ventricle relaxation rate during the SBT seems to be the key factor of weaning failure. In contrast, the systolic dysfunction was not associated with weaning outcome.

Diagnostic performance of fractional excretion of urea in the evaluation of critically ill patients with acute kidney injury: a multicenter cohort study

IntroductionSeveral factors, including diuretic use and sepsis, interfere with the fractional excretion of sodium, which is used to distinguish transient from persistent acute kidney injury (AKI). These factors do not affect the fractional excretion of urea (FeUrea). However, there are conflicting data on the diagnostic accuracy of FeUrea.MethodsWe conducted an observational, prospective, multicenter study at three ICUs in university hospitals. Unselected patients, except those with obstructive AKI, were admitted to the participating ICUs during a six-month period. Transient AKI was defined as AKI caused by renal hypoperfusion and reversal within three days. The results are reported as medians (interquartile ranges).ResultsA total of 203 patients were included. According to our definitions, 67 had no AKI, 54 had transient AKI and 82 had persistent AKI. FeUrea was 39% (28 to 40) in the no-AKI group, 41% (29 to 54) in the transient AKI group and 32% (22 to 51) in the persistent AKI group (P = 0.12). FeUrea was of little help in distinguishing transient AKI from persistent AKI, with the area under the receiver operating characteristic curve being 0.59 (95% confidence interval, 0.49 to 0.70; P = 0.06). Sensitivity was 63% and specificity was 54% with a cutoff of 35%. In the subgroup of patients receiving diuretics, the results were similar.ConclusionsFeUrea may be of little help in distinguishing transient AKI from persistent AKI in critically ill patients, including those receiving diuretic therapy. Additional studies are needed to evaluate alternative markers or strategies to differentiate transient from persistent AKI.

Diagnostic accuracy of early urinary index changes in differentiating transient from persistent acute kidney injury in critically ill patients: multicenter cohort study

IntroductionUrinary indices have limited effectiveness in separating transient acute kidneyinjury (AKI) from persistent AKI in ICU patients. Their time-course may vary withthe mechanism of AKI. The primary objective of this study was to evaluate thediagnostic value of changes over time of the usual urinary indices in separatingtransient AKI from persistent AKI.MethodsAn observational prospective multicenter study was performed in six ICUs involving244 consecutive patients, including 97 without AKI, 54 with transient AKI, and 93with persistent AKI. Urinary sodium, urea and creatinine were measured at ICUadmission (H0) and on 6-hour urine samples during the first 24 ICU hours (H6, H12,H18, and H24). Transient AKI was defined as AKI with a cause for renalhypoperfusion and reversal within 3 days.ResultsSignificant increases from H0 to H24 were noted in fractional excretion of urea(median, 31% (22 to 41%) and 39% (29 to 48%) at H24, P < 0.0001),urinary urea/plasma urea ratio (15 (7 to 28) and 20 (9 to 40), P <0.0001), and urinary creatinine/plasma creatinine ratio (50 (24 to 101) and 57 (29to 104), P = 0.01). Fractional excretion of sodium did not changesignificantly during the first 24 hours in the ICU (P = 0.13). Neitherurinary index values at ICU admission nor changes in urinary indices between H0and H24 performed sufficiently well to recommend their use in clinical setting(area under the receiver-operating characteristic curve ≤0.65).ConclusionAlthough urinary indices at H24 performed slightly better than those at H0 indifferentiating transient AKI from persistent AKI, they remain insufficientlyreliable to be clinically relevant.

CT-Guided Percutaneous Catheter Drainage of Acute Infectious Necrotizing Pancreatitis: Assessment of Effectiveness and Safety

OBJECTIVE The purpose of this study is to assess retrospectively the effectiveness and safety of CT-guided percutaneous drainage and to determine the factors influencing clinical success and mortality in patients with infectious necrotizing pancreatitis. MATERIALS AND METHODS From April 1997 to December 2005, 48 consecutive patients (33 men and 15 women; median age, 58.5 years) with proven infectious necrotizing pancreatitis underwent percutaneous catheter drainage via CT guidance. Evaluated factors included clinical, biologic, and radiologic scores; drainage and catheter characteristics; and complications. Clinical success was defined as control of sepsis without requirement for surgery. Univariate analysis was performed to determine factors that could have affected the clinical success and the mortality rates. RESULTS Clinical success was achieved in 31 of 48 patients (64.6%) and was significantly associated with Ranson score (p = 0.01) and with the delay between admission and the beginning of the drainage (p = 0.005), with a calculated threshold delay of 18 days (p = 0.001). The global mortality rate (14/48 [29%]) was also influenced by the Ranson score (p = 01) and the delay of drainage (p = 0.04) with the same threshold delay (p = 0.01). Only two major nonlethal procedure-related complications were observed. CONCLUSION Percutaneous catheter drainage is a safe and effective technique to treat acute infectious necrotizing pancreatitis.

Unusual Cutaneous Manifestations of Miliary Tuberculosis

Cutaneous manifestations of miliary tuberculosis are extremely rare. We describe a 62-year-old woman with leukopenia who developed infiltrated dermal-hypodermal and ulcerative cutaneous lesions during the course of miliary tuberculosis. Miliary tuberculosis was diagnosed when Mycobacterium tuberculosis bacilli were isolated by cultures of the bronchoalveolar lavage fluid and blood and when acid-fast bacilli were detected on histopathologic examination of hepatic, pulmonary, and cutaneous biopsy specimens. With the increasing incidence of immunocompromised patients, unusual presentations of tuberculosis may be observed more often. Acute miliary tuberculosis of the skin is an exceptional manifestation that is due to acute hematogenous dissemination of M. tuberculosis to the skin. We describe a patient who had unusual cutaneous manifestations of miliary tuberculosis.

The early phase of human sepsis is characterized by a combination of apoptosis and proliferation of T cells

PURPOSE T cell activation as well as unresponsiveness has been described in separate studies in sepsis. Our aim was to establish the coexistence of both T cell fate in human sepsis. PATIENTS AND METHODS This is a cross-sectional study of 48 patients presenting with severe sepsis or septic shock and 15 healthy controls. Cytofluorometric techniques were used to quantify T cell activation, apoptosis, proliferation, expression of costimulatory molecules, and cytokine secretion. RESULTS Patients with sepsis were characterized by a significant increase in the percentage of activated T cell subsets, as measured using CD69 marker, compared with healthy controls (P<.05). T cell proliferation as measured through Ki67 expression was obvious in infected patients for both CD4 and CD8 T cell subsets compared with controls (P ≤.006). T cell subset apoptosis as measured using Hoechst dye was also increased in infected patients compared with controls (P ≤.002). CD4 T cell proliferation was correlated with interleukin 2 secretion (R(2)=0.84, P<.001), whereas up-regulation of CD4 T cell apoptosis was correlated with CTLA-4 expression (R(2)=0.24, P=.001). No such similar relationship was observed for CD8(+) T cells. CONCLUSIONS Concomitant T cell proliferation and T cell apoptosis are observed in human sepsis, being related to a different pathway.

Idiopathic Acute Eosinophilic Pneumonia Requiring ECMO in a Teenager Smoking Tobacco and Cannabis

We describe what we believe is an entirely novel case of a 15‐year‐old boy with idiopathic acute eosinophilic pneumonia and unusual, resistant hypoxemia which necessitated extracorporeal membrane oxygenation. Response to corticosteroids was excellent and a full recovery was observed. Smoking cigarettes and cannabis on the day the symptoms began may have contributed to the occurrence of this rare disease. Pediatr Pulmonol. 2010;45:1246–1249.