Frédéric M. Jacobs

Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study

Introduction: Because of disturbed renal autoregulation, patients experiencing hypotension-induced renal insult might need higher levels of mean arterial pressure (MAP) than the 65 mmHg recommended level in order to avoid the progression of acute kidney insufficiency (AKI). Methods: In 217 patients with sustained hypotension, enrolled and followed prospectively, we compared the evolution of the mean arterial pressure (MAP) during the first 24 hours between patients who will show AKI 72 hours after inclusion (AKIh72) and patients who will not. AKIh72 was defined as the need of renal replacement therapy or “Injury” or “Failure” classes of the 5-stage RIFLE classification (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) for acute kidney insufficiency using the creatinine and urine output criteria. This comparison was performed in four different subgroups of patients according to the presence or not of AKI at the sixth hour after inclusion (AKIh6 as defined as a serum creatinine level above 1.5 times baseline value within the first six hours) and the presence or not of septic shock at inclusion.The ability of MAP averaged over H6 to H24 to predict AKIh72 was assessed by the area under the receiver operating characteristic curve (AUC) and compared between groups. Results: The MAP averaged over H6 to H24 or over H12 to H24 was significantly lower in patients who showed AKIh72 than in those who did not, only in septic shock patients with AKIh6, whereas no link was found between MAP and AKIh72 in the three others subgroups of patients. In patients with septic shock plus AKIh6, MAP averaged over H6 to H24 or over H12 to H24 had an AUC of 0.83 (0.72 to 0.92) or 0.84 (0.72 to 0.92), respectively, to predict AKIh72 . In these patients, the best level of MAP to prevent AKIh72 was between 72 and 82 mmHg. Conclusions: MAP about 72 to 82 mmHg could be necessary to avoid acute kidney insufficiency in patients with septic shock and initial renal function impairment.

Functional outcome after convulsive status epilepticus.

Objectives:Few outcome data are available about convulsive status epilepticus managed in the intensive care unit. We studied 90-day functional outcomes and their determinants in patients with convulsive status epilepticus. Design:Two hundred forty-eight convulsive status epilepticus patients admitted to 18 intensive care units in 2005–2007 were included in a prospective observational cohort study. The main outcome measure was a Glasgow Outcome Scale score of 5 (good recovery) on day 90. Main Results:Convulsive status epilepticus occurred out of hospital in 177 (67%) patients, and all but 15 patients were still seizing at medical team arrival. The median time from convulsive status epilepticus onset to anticonvulsant drug initiation was 40 mins (interquartile range, 5–80). Total seizure duration was 85 mins (interquartile range, 46.5–180). Convulsive status epilepticus was refractory in 49 (20%) patients. The most common causes of convulsive status epilepticus were anticonvulsive agent withdrawal (36.4%) in patients with previous epilepsy and stroke (27.7%) in inaugural convulsive status epilepticus. Mechanical ventilation was needed in 210 (85%) patients. On day 90, 42 (18.8%) patients were dead, 87 (38.8%) had marked functional impairments (Glasgow Outcome Scale score, 2–4), and 95 (42.4%) had a good recovery (Glasgow Outcome Scale score, 5). Factors showing independent positive associations with poor outcome (Glasgow Outcome Scale score, <5) were older age (odds ratio, 1.04/year; 95% confidence interval, 1.02–1.05; p = .0005), cerebral insult (odds ratio, 2.70; 95% confidence interval, 1.37–5.26; p = .007), longer seizure duration (odds ratio, 1.72/120 min; 95% confidence interval, 1.05–2.86; p = .03), on-scene focal neurologic signs (odds ratio, 2.08; 95% confidence interval, 1.03–4.16; p = .04), and refractory convulsive status epilepticus (odds ratio, 2.70; 95% confidence interval, 1.02–7.14; p = .045). Conclusions:Ninety days after intensive care unit admission for convulsive status epilepticus, half the survivors had severe functional impairments. Longer seizure duration, cerebral insult, and refractory convulsive status epilepticus were strongly associated with poor outcomes, suggesting a role for early neuroprotective strategies.

Increased diffusion of soluble adhesion molecules in meningitis, severe sepsis and systemic inflammatory response without neurological infection is associated with intrathecal shedding in cases of meningitis

ObjectiveSepsis and systemic inflammatory response syndrome (SIRS) result in the release in plasma of inflammatory cytokines and soluble forms of adhesion molecules in relation to endothelial activation. This study was designed to compare cerebrospinal fluid (CSF) concentrations of adhesion molecules in meningitis and SIRS without neurological infection and to evaluate in meningitis whether they originate from passive diffusion through damaged blood–CSF barrier or from local production.DesignProspective observational study.SettingUniversity hospital medical intensive care unit.PatientsNineteen patients with meningitis and 41 patients with sepsis or SIRS without cerebrospinal infection consecutively admitted to the critical care unit over an 18-month period.InterventionsSoluble forms of adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (interleukin (IL)-1β and TNF−α) were measured in paired CSF and blood samples.ResultsSerum concentrations of soluble adhesion molecules and cytokines were increased in the two groups, without significant differences. The CSF concentrations were elevated in both cases, whereas patients with meningitis demonstrated significantly higher CSF concentrations of soluble ICAM-1, VCAM-1, E-selectin, and TNF-α (p<0.001), with higher corresponding CSF/serum ratios. Correlations between CSF and serum concentrations were found only in meningitis. These correlations were strong for soluble ICAM-1 (r2=0.7, p<0.001) and E-selectin (r2=0.9, p<0.001), but weaker for VCAM-1. VCAM-1 CSF/serum ratios were increased, in comparison with ICAM-1 and E-selectin CSF/serum ratios, despite similar molecular weights. Serum and CSF levels of cytokines and adhesion molecules were not predictive of death for the whole population, except concentrations of ICAM-1 significantly increased in non-surviving patients (p<0.05).ConclusionsThe CSF soluble adhesion molecules are increased in sepsis, SIRS and meningitis. In meningitis, the correlation between CSF and serum concentrations of adhesion molecules and the presence of a discrepancy of CSF/serum ratios for molecules of the same molecular weight may suggest intrathecal shedding in addition to diffusion through blood–CSF barrier.

Cardiac troponin level is not an independent predictor of mortality in septic patients requiring medical intensive care unit admission

Turley and Gedney claim that the cardiac troponin Ic level is a predictor of adverse outcome [1] and that their results support those of King and colleagues [2]. Unfortunately, King and colleagues were unable to demonstrate a link between the troponin Ic level and mortality when using a multivariate model including the Acute Physiology Age and Chronic Health Evaluation II score. Interpretation of the results of Turley and Gedney therefore requires caution since their results are based only on univariate analysis [1]. We prospectively evaluated the accuracy of cardiac troponin Ic levels to predict inhospital mortality in 118 adults with documented sepsis and no history of cardiac arrest or acute coronary syndrome, and we then compared this accuracy with the performance of the new Simplified Acute Physiology II score. Seventy-five patients (63.6%) were in shock (systolic blood pressure <90 mmHg), while 58 patients (49%) had a cardiac troponin Ic level greater than 0.3 ng/ml (detection limit, 0.15 ng/ml) and 43 patients (36.4%) a level greater than 1 ng/ml. Nonsurvivors were more severely ill (Simplified Acute Physiology II score [mean ± standard deviation], 74.7 ± 25.2 versus 51.5 ± 18.4; P < 0.001), tended to have higher cardiac troponin Ic levels (5.5 ± 10.3 ng/ml versus 3.6 ± 8.9 ng/ml) and tended to be older. Patients with a cardiac troponin Ic level above 0.3 ng/ml had a twofold risk of dying (odds ratio, 2.56; 95% confidence interval, 1.89–5.542), but the predictive abilities for mortality of cardiac troponin Ic were poor according to the area under the curve of the receiver– operating characteristic curve (0.612; 95% confidence interval, 0.504–0.719) – in contrast to the Simplified Acute Physiology II score (0.775; 95% confidence interval, 0.686–0.864). A logistic regression model identified only the Simplified Acute Physiology II score as an independent predictor of death (β = 0.048; odds ratio, 1.049; 95% confidence interval, 1.028–1.075; per point increment, P < 0.001). We confirm that nearly one-half of patients with severe sepsis have an elevated cardiac troponin Ic level within the first 72 hours of the intensive care unit stay [3-7]. Whereas there is convincing evidence that the cardiac troponin Ic level reflects and correlates with myocardial damage in septic patients whatever the mechanism [3-6] and that every elevated troponin level should not be diagnosed or treated as acute coronary syndrome [7], the impact of an elevated troponin level on the outcome remains a matter of debate, even in studies performing multivariate analysis [2,3,5-7]. Although two series found that mortality was dependent on the troponin level [3,5], like other studies [2,6,7] we failed to reach a similar conclusion. In our opinion, the troponin level can be useful to assess the risk of myocardial dysfunction in patients with sepsis but is not an independent marker of mortality.

Pneumopathie à mycoplasme : une cause rare de syndrome de détresse respiratoire aiguë (SDRA) et de résistance potentielle aux antibiotiques

INTRODUCTION Acute respiratory distress syndrome caused by Mycoplasma pneumoniae infection has rarely been described. OBSERVATION We report a case of community-acquired pneumonia occurring in a patient with Downs syndrome. Persisting hypoxemia raised the questions of nosocomial pneumonia, of the occurrence of a fibrosing alveolitis or of the resistance of the strain to macrolides. After a long period of very severe respiratory impairment, the evolution was progressively favourable and the patient was discharged from ICU with full respiratory recovery 43 days after admission. CONCLUSION Acute respiratory distress syndrome caused by M. pneumoniae infection is rare but must be considered when the appropriate clinical and radiological pattern occurs. The question of the susceptibility of the strain to macrolides has to be raised in some circumstances.

Handgrip Strength Predicts Difficult Weaning But Not Extubation Failure in Mechanically Ventilated Subjects

BACKGROUND: Muscle weakness, defined by the Medical Research Council scale, has been associated with delay in mechanical ventilation weaning. In this study, we evaluated handgrip strength as a prediction tool in weaning outcome. METHODS: This was a 1-y prospective study in 2 ICUs in 2 university hospitals. Adult patients who were on mechanical ventilation for at least 48 h and eligible for mechanical ventilation weaning were screened for inclusion. Handgrip strength was evaluated using a handheld dynamometer before each spontaneous breathing trial (SBT). Attending physicians were unaware of handgrip strength and decided on extubation according to guidelines. RESULTS: Eighty-four subjects were included (median age 66 [53–79] y, with a median Simplified Acute Physiology Score II of 49 [37–63]). At the first evaluation, median handgrip strength was significantly associated with weaning outcome as defined by international guidelines: simple (20 [12–26] kg), difficult (12 [6–21] kg), or prolonged (6 [3–11] kg) weaning (P = .008). Time to liberation from mechanical ventilation and ICU stay were significantly longer for subjects classified as having muscle weakness according to the handgrip strength-derived definition (P = .02 and P = .03, respectively). In multivariate analysis, known history of COPD (odds ratio [OR] 5.48, 95% CI 1.44–20.86, P = .01), sex (OR 6.16, 95% CI 1.64–23.16, P = .007), and handgrip strength at the first SBT (OR 0.89, 95% CI 0.85–0.97, P = .004) were significantly associated with difficult or prolonged weaning. Extubation failure, as defined by re-intubation or unscheduled noninvasive ventilation within 48 h after extubation, occurred 14 times after 92 attempts, leading to an extubation failure rate of 15%. No association was found between handgrip strength and extubation outcome. CONCLUSIONS: Muscle weakness, assessed by handgrip strength, is associated with difficult or prolonged mechanical ventilation weaning and ICU stay, but not with extubation outcome.

Cas cliniquePneumopathie à mycoplasme : une cause rare de syndrome de détresse respiratoire aiguë (SDRA) et de résistance potentielle aux antibiotiquesMycoplasma-related pneumonia: A rare cause of acute respiratory distress syndrome (ARDS) and of potential antibiotic resistance

INTRODUCTION Acute respiratory distress syndrome caused by Mycoplasma pneumoniae infection has rarely been described. OBSERVATION We report a case of community-acquired pneumonia occurring in a patient with Downs syndrome. Persisting hypoxemia raised the questions of nosocomial pneumonia, of the occurrence of a fibrosing alveolitis or of the resistance of the strain to macrolides. After a long period of very severe respiratory impairment, the evolution was progressively favourable and the patient was discharged from ICU with full respiratory recovery 43 days after admission. CONCLUSION Acute respiratory distress syndrome caused by M. pneumoniae infection is rare but must be considered when the appropriate clinical and radiological pattern occurs. The question of the susceptibility of the strain to macrolides has to be raised in some circumstances.

Renal Replacement Therapy in Patients with Severe Precapillary Pulmonary Hypertension with Acute Right Heart Failure

Background: Renal replacement therapy has been suggested as a therapeutic option in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension. However, there are few data supporting this strategy. Objectives: To describe the clinical course and the prognosis of pulmonary hypertensive patients undergoing renal replacement therapy in the setting of acute right heart failure. Methods: This was a single-center retrospective study over an 11-year period. Data were collected from all patients with chronic precapillary pulmonary hypertension requiring catecholamine infusions for clinical worsening and acute kidney injury that necessitated renal replacement therapy. Results: Fourteen patients were included. At admission, patients had a blood urea of 28.2 mmol/l (22.3-41.2), a creatinine level of 496 µmol/l (304-590), and a mean urine output in the 24 h preceding hospitalization of 200 ml (0-650). Sixty-eight renal replacement therapy sessions were performed, 36 of which were continuous and 32 of which were intermittent. Systemic hypotension occurred in 16/32 intermittent and 16/36 continuous sessions (p = 0.9). Two patients died during a continuous session. The intensive care unit-related, 1-, and 3-month mortality was 46.7, 66.7, and 73.3%, respectively. Conclusion: Renal replacement therapy is feasible in the setting of acute right ventricular failure in patients with severe precapillary pulmonary hypertension but is associated with a poor prognosis. The best modality and timing in this population remain to be defined.

Bronchoalveolar lavage cytological alveolar damage in patients with severe pneumonia

IntroductionHistological examination of lung specimens from patients with pneumonia shows the presence of desquamated pneumocytes and erythrophages. We hypothesized that these modifications should also be present in bronchoalveolar lavage fluid (BAL) from patients with hospital-acquired pneumonia.MethodsWe conducted a prospective study in mechanically ventilated patients with clinical suspicion of pneumonia. Patients were classified as having hospital-acquired pneumonia or not, in accordance with the quantitative microbiological cultures of respiratory tract specimens. A group of severe community-acquired pneumonias requiring mechanical ventilation during the same period was used for comparison. A specimen of BAL (20 ml) was taken for cytological analysis. A semiquantitative analysis of the dominant leukocyte population, the presence of erythrophages/siderophages and desquamated type II pneumocytes was performed.ResultsIn patients with confirmed hospital-acquired pneumonia, we found that 13 out of 39 patients (33.3%) had erythrophages/siderophages in BAL, 18 (46.2%) had desquamated pneumocytes and 8 (20.5%) fulfilled both criteria. Among the patients with community-acquired pneumonia, 7 out of 15 (46.7%) had erythrophages/siderophages and 6 (40%) had desquamated pneumocytes on BAL cytology. Only four (26.7%) fulfilled both criteria. No patient without hospital-acquired pneumonia had erythrophages/siderophages and only 3 out of 18 (16.7%) had desquamated pneumocytes on BAL cytology.ConclusionCytological analysis of BAL from patients with pneumonia (either community-acquired or hospital-acquired) shows elements of cytological alveolar damage as hemorrhage and desquamated type II pneumocytes much more frequently than in BAL from patients without pneumonia. These elements had a high specificity for an infectious cause of pulmonary infiltrates but low specificity. These lesions could serve as an adjunct to diagnosis in patients suspected of having ventilator-associated pneumonia.

Carboplatin: a new cause of severe type B lactic acidosis secondary to mitochondrial DNA damage.

In adults, type B lactic acidosis is rare and generally associated with a toxin, particularly metformin or antiretroviral nucleosides analogues. We report a case of lactic acidosis caused by carboplatin in a 50-year-old woman suffering from primary peritoneal carcinoma. She was admitted for severe lactic acidosis (pH 6.77, lactate 19 mmol/L) associated with multiple organ failure (PaO₂/FiO₂ 96, creatinine 231 μmol/L, aspartate aminotransferase > 25,000 UI, factor V 13%) occurring during the sixth carboplatin cycle. In the absence of sepsis, internal bleeding, alcohol poisoning, or other causes of lactic acidosis, the hypothesis of mitochondrial DNA (mtDNA) damage secondary to carboplatin and subsequent mitochondrial dysfunction leading to increase in glycolysis and lactic acidosis was suspected. L-Carnitine therapy associated with aggressive intensive care support led to a progressive improvement (pH 7.29, bicarbonate 24 mmol/L, lactate 7.8 mmol/L), but life support was withdrawn on day 7 because of peritoneal relapse. A respiratory chain dysfunction of enzyme activities encoded by mtDNA and multiple mtDNA deletions were found in muscle and liver tissue. It is generally accepted that carboplatin toxicity results in bone marrow suppression, renal dysfunction, or neurotoxicity and that platinating agents have no direct mitochondrial effect. However, although very unusual, emergency physicians must be aware that carboplatin can cause mitochondrial toxicity and trigger lactic acidosis.