Louis Puybasset

Regional distribution of gas and tissue in acute respiratory distress syndrome. I. Consequences for lung morphology

Objective: To compare the computed tomographic (CT) analysis of the distribution of gas and tissue in the lungs of patients with ARDS with that in healthy volunteers. Design: Prospective study over a 53-month period.¶Setting: Fourteen-bed surgical intensive care unit of a university hospital. Patients and participants: Seventy-one consecutive patients with early ARDS and 11 healthy volunteers. Measurements and results: A lung CT was performed at end-expiration in patients with ARDS (at zero PEEP) and healthy volunteers. In patients with ARDS, end-expiratory lung volume (gas + tissue) and functional residual capacity (FRC) were reduced by 17 % and 58 % respectively, and an excess lung tissue of 701 ± 321 ml was observed. The loss of gas was more pronounced in the lower than in the upper lobes. The lower lobes of 27 % of the patients were characterized by “compression atelectasis,” defined as a massive loss of aeration with no concomitant excess in lung tissue, and “inflammatory atelectasis,” defined as a massive loss of aeration associated with an excess lung tissue, was observed in 73 % of the patients. Three groups of patients were differentiated according to the appearance of their CT: 23 % had diffuse attenuations evenly distributed in the two lungs, 36 % had lobar attenuations predominating in the lower lobes, and 41 % had patchy attenuations unevenly distributed in the two lungs. The three groups were similar regarding excess lung tissue in the upper and lower lobes and reduction in FRC in the lower lobes. In contrast, the FRC of the upper lobes was markedly lower in patients with diffuse or patchy attenuations than in healthy volunteers or patients with lobar attenuations. Conclusions: These results demonstrate that striking differences in lung morphology, corresponding to different distributions of gas within the lungs, are observed in patients whose respiratory condition fulfills the definition criteria of ARDS.

Acute respiratory distress syndrome: lessons from computed tomography of the whole lung.

ObjectiveThis review aims to show how computed tomography of the whole lung has modified our view of acute respiratory distress syndrome, and why it impacts on the optimization of the ventilatory strategy. Data sourcesComputed tomography allows an accurate assessment of the volumes of gas and lung tissue, respectively, and lung aeration. If computed tomographic sections are contiguous from the apex to the lung base, quantitative analysis can be performed either on the whole lung or, regionally, at the lobar level. Analysis requires a manual delineation of lung parenchyma and is facilitated by software, including a color-coding system that allows direct visualization of overinflated, normally aerated, poorly aerated, and nonaerated lung regions. In addition, lung recruitment can be measured as the amount of gas that penetrates poorly aerated and nonaerated lung regions after the application of positive intrathoracic pressure. Data SummaryThe lung in acute respiratory distress syndrome is characterized by a marked increase in lung tissue and a massive loss of aeration. The former is homogeneously distributed, although with a slight predominance in the upper lobes, whereas the latter is heterogeneously distributed. The lower lobes are essentially nonaerated, whereas the upper lobes may remain normally aerated, despite a substantial increase in regional lung tissue. The overall lung volume and the cephalocaudal lung dimensions are reduced primarily at the expense of the lower lobes, which are externally compressed by the heart and abdominal content when the patient is in the supine position. Two opposite radiologic presentations, corresponding to different lung morphologies, can be observed. In patients with focal computed tomographic attenuations, frontal chest radiography generally shows bilateral opacities in the lower quadrants and may remain normal, particularly when the lower lobes are entirely atelectatic. In patients with diffuse computed tomographic attenuations, the typical radiologic presentation of “white lungs” is observed. If these patients lie supine, lung volume is preserved in the upper lobes and reduced in the lower lobes, although the loss of aeration is equally distributed between the upper and lower lobes. This observation does not support the “opening and collapse concept” described as the “sponge model.” In fact, interstitial edema, alveolar flooding, or both, not collapse, are histologically present in all regions of the lung in acute respiratory distress syndrome. Compression atelectasis is observed only in caudal parts of the lung, where external forces (such as cardiac weight, abdominal pressure, and pleural effusion) tend to squeeze the lower lobes. When a positive intrathoracic pressure is applied to patients with focal acute respiratory distress syndrome, poorly aerated and nonaerated lung regions are recruited, whereas lung regions that are normally aerated at zero end-expiratory pressure tend to be rapidly overinflated, increasing the risk of ventilator-induced lung injury. ConclusionSelection of the optimal positive end-expiratory pressure level should not only consider optimizing alveolar recruitment, it should also focus on limiting lung overinflation and counterbalancing compression of the lower lobes by maneuvers such as appropriate body positioning. Prone and semirecumbent positions facilitate the reaeration of dependent and caudal lung regions by partially relieving cardiac and abdominal compression and may improve gas exchange.

Inhaled Nitric Oxide Reverses the Increase in Pulmonary Vascular Resistance Induced by Permissive Hypercapnia in Patients with Acute Respiratory Distress Syndrome

BackgroundThe aim of this prospective study was to determine if inhaled nitric oxide (NO) would reverse the increase in pulmonary arterial pressures and in pulmonary vascular resistance induced by acute permissive hypercapnia in patients with acute respiratory distress syndrome. MethodsIn 11 critically ill patients (mean age 59 ± 22 yr) with acute respiratory distress syndrome (Murray Score 2.5), the lungs were mechanically ventilated with NO 2 ppm during both normocapnic and hypercapnic conditions. Four phases were studied: normocapnla (arterial carbon dioxide tension 38 ± 6 mmHg, tidal volume 655 ± 132 ml); normocapnia plus inhaled NO 2 ppm; hypercapnia (arterial carbon dioxide tension 65 ± 15 mmHg, tidal volume 330 ± 93 ml); and hypercapnia plus inhaled NO 2 ppm. Continuous recordings were made of heart rate, arterial pressure, pulmonary artery pressure, tracheal pressure, and tidal volume (by pneumotachograph). At the end of each condition, arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac output were measured. Simultaneous arterial and mixed venous blood samples were obtained to measure arterial oxygen tension, arterial carbon dioxide tension, mixed venous oxygen tension, arterial hemoglobin oxygen saturation, mixed venous hemoglobin oxygen saturation, pH, and blood hemoglobin and methemoglobin concentrations (by hemoximeter). In addition, plasma concentrations of catecholamines were measured with a radioenzymatic assay. In 5 patients, end-tidal carbon dioxide tension was measured with a nonaspirative infrared capnometer. Calculations were made of pulmonary vascular resistance index, systemic vascular resistance index, true pulmonary shunt, and alveolar dead space. ResultsDuring hypercapnia, NO decreased pulmonary vascular resistance Index from 525 ± 223 to 393 ± 142 dyn. s. cm−5. m−2 (P < 0.01), a value similar to that measured in normocapnic conditions (391 ± 122 dyn. s. cm−5. m−2). It also reduced mean pulmonary artery pressure from 40 ± 9 to 35 ± 8 mmHg (P < 0.01). NO increased arterial oxygen tension (inspired oxygen fraction 1) from 184 ± 67 to 270 ± 87 mmHg during normocapnia and from 189 ± 73 to 258 ± 101 mmHg during hypercapnia (P < 0.01). NO decreased true pulmonary shunt during normocapnia (from 34 ± 3% to 28 ± 4%, P < 0.001) but had no significant effect on it during hypercapnia (39 ± 7% vs. 38 ± 8.5%). In five patients, NO resulted in a decrease in alveolar dead space from 34 ± 7% to 28 ± 10% in normocapnic conditions and from 30 ± 9% to 22 ± 10% in hypercapnic conditions (P < 0.05). ConclusionsInhaled NO completely reversed the increase in pulmonary vascular resistance Index induced by acute permissive hypercapnia. It only partially reduced the pulmonary hypertension induced by acute permissive hypercapnia, probably because the flow component of the Increase in pulmonary pressure (i.e., the increase in cardiac output) was not reduced by inhaled NO. A significant increase in arterial oxygenation after NO administration was observed during normocapnic and hypercapnic conditions. A ventilation strategy combining permissive hypercapnia and inhaled NO may reduce the potentially deleterious effects that permissive hypercapnia alone has on lung parenchyma and pulmonary circulation.

Risk factors for neurosurgical site infections after craniotomy : a critical reappraisal of antibiotic prophylaxis on 4578 patients

The objective of this study was to evaluate incidence and risk factors of postoperative infections, with emphasis on antibiotic prophylaxis, in a series of 4578 craniotomies. A prospective database was implemented for surveillance of postcraniotomy infections. During period A, no antibiotic prophylaxis was prescribed for scheduled, clean craniotomies, lasting less than 4 h, whereas emergency, clean-contaminated or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. During period B, prophylaxis was given to every craniotomy. The effect of prophylaxis on craniotomy infections, independently of other risk factors, was studied by multivariate analysis. The overall infection rate was 6.6%. CSF leak, male gender, surgical diagnosis, surgeon, early re-operation, surgical duration and absence of prophylaxis were independent risk factors. CSF leak had the highest odds ratio. Antibiotic prophylaxis decreased infection rate from 9.7% down to 5.8% in the entire population (p < 0.0001) mainly by decreasing rates in low risk patients from 10.0% down to 4.6% (p < 0.0001). Antibiotic prophylaxis in craniotomy is effective in preventing surgical site infections even in low-risk patients.

Regional distribution of gas and tissue in acute respiratory distress syndrome. II. Physiological correlations and definition of an ARDS Severity Score

Objectives: (a) To assess whether differences in lung morphology observed in patients with adult respiratory distress syndrome (ARDS) are associated with differences in cardiorespiratory parameters, lung mechanics, and outcome. (b) To propose a new ARDS Severity Score to identify patients with a high mortality risk. Design: Prospective study over a 53-month period. Setting: Fourteen-bed surgical intensive care unit of a university hospital. Patients and participants: Seventy-one consecutive patients with early ARDS. Measurements and results: Cardiorespiratory parameters were measured using a Swan-Ganz catheter, the pressure-volume (PV) curve was measured using the gross syringe method, and fast spiral computed tomography (CT) was performed. Patients with diffuse attenuations (n = 16) differed from patients with lobar attenuations (n = 26) regarding: (a) mortality rate (75 % vs. 42 %, p = 0.05), (b) incidence of primary ARDS (82 % vs. 50 %, p = 0.03), (c) respiratory compliance (47 ± 12 vs. 64 ± 16 ml per cmH2O–1p = 0.04), and (d) lower inflexion point (8.4 ± 2.0 vs. 4.6 ± 2.0 cmH2O, p = 0.001). A third group of patients with patchy attenuations (n = 29) had a mortality rate of 41 %, a respiratory compliance of 56 ± 18 ml per cmH2O–1 and a lower inflexion point of 6.3 ± 2.7 cmH2O. The bedside chest radiograph accurately assessed lung morphology in only 42 % of the patients. In contrast to the scores based on the bedside chest radiograph, a new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters identified a subgroup of patients with a high mortality rate (≥ 60 %). Conclusions: In patients with ARDS, differences in lung morphology are associated with differences in outcome and lung mechanics. A new ARDS Severity Score based on CT lung morphology and cardiorespiratory parameters accurately identified patients with the most severe forms of ARDS and a mortality rate above 60 %.

Risk factors for adult nosocomial meningitis after craniotomy: role of antibiotic prophylaxis.

OBJECTIVE To evaluate incidence and risk factors of postoperative meningitis, with special emphasis on antibiotic prophylaxis, in a series of 6243 consecutive craniotomies. METHODS Meningitis was individualized from a prospective surveillance database of surgical site infections after craniotomy. Ventriculitis related to external ventricular drainage or cerebrospinal fluid shunt were excluded. From May 1997 until March 1999, no antibiotic prophylaxis was prescribed for scheduled, clean, lasting less than 4 hours craniotomies, whereas emergency, clean-contaminated, or long-lasting craniotomies received cloxacillin or amoxicillin-clavulanate. From April 1999 until December 2003, prophylaxis was given to every craniotomy. Independent risk factors for meningitis were studied by a multivariate analysis. Efficacy of antibiotic prophylaxis in preventing meningitis was studied as well as consequences on bacterial flora. RESULTS The overall meningitis rate was 1.52%. Independent risk factors were cerebrospinal fluid leakage, concomitant incision infection, male sex, and surgical duration. Antibiotic prophylaxis reduced incision infections from 8.8% down to 4.6% (P < 0.0001) but did not prevent meningitis: 1.63% in patients without antibiotic prophylaxis and 1.50% in those who received prophylaxis. Bacteria responsible for meningitis were mainly noncutaneous in patients receiving antibiotics and cutaneous in patients without prophylaxis. In the former, microorganisms tended to be less susceptible to the prophylactic antibiotics administered. Mortality rate was higher in meningitis caused by noncutaneous bacteria as compared with those caused by cutaneous microorganisms. CONCLUSION Perioperative antibiotic prophylaxis, although clearly effective for the prevention of incision infections, does not prevent meningitis and tends to select prophylaxis resistant microorganisms.

Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma

Oligodeoxynucleotides containing CpG motifs (CpG ODNs) display a strong immunostimulating activity and drive the immune response toward the Th1 (T helper type 1) phenotype. These ODNs have shown promising efficacy in preclinical studies when injected locally in several cancer models. We conducted a phase 1 trial to define the safety profile of CpG-28, a phosphorothioate CpG ODN, administered intratumorally by convection-enhanced delivery in patients with recurrent glioblastoma. Cohorts of three to six patients were treated with escalating doses of CpG-28 (0.5-20 mg), and patients were observed for at least four months. Twenty-four patients entered the trial. All patients had previously been treated with radiotherapy, and most patients had received one or several types of chemotherapy. Median age was 58 years (range, 25-73) and median KPS was 80% (range, 60%-100%). Adverse effects possibly or probably related to the studied drug were moderate and consisted mainly in worsening of neurological conditions (four patients), fever above 38 degrees C that disappeared within a few days (five patients), and reversible grade 3 lymphopenia (seven patients). Only one patient experienced a dose-limiting toxicity. Preliminary evidence of activity was suggested by a minor response observed in two patients and an overall median survival of 7.2 months. In conclusion, CpG-28 was well tolerated at doses up to 20 mg per injection in patients with recurrent glioblastoma. Main side effects were limited to transient worsening of neurological condition and fever.

Experience of diffusion tensor imaging and 1H spectroscopy for outcome prediction in severe traumatic brain injury: Preliminary results.

Objective: The objective of the study is to test whether multimodal magnetic resonance imaging can provide a reliable outcome prediction of the clinical status, focusing on consciousness at 1 year after severe traumatic brain injury (TBI). Design: Single center prospective cohort with consecutive inclusions. Setting: Critical Care Neurosurgical Unit of a university hospital. Patients: Forty-three TBI patients not responding to simple orders after sedation cessation and 15 healthy controls. Interventions: A multimodal magnetic resonance imaging combining morphologic sequences, diffusion tensor imaging (DTI), and 1H proton magnetic resonance spectroscopy (MRS) was performed 24 ± 11 days after severe TBI. The ability of DTI and MRS to predict 1-year outcome was assessed by linear discriminant analysis (LDA). Robustness of the classification was tested using a bootstrap procedure. Measurements and Main Results: Fractional anisotropy (FA) was computed as the mean of values at discrete brain sites in the infratentorial and supratentorial regions. The N-acetyl aspartate/creatine (NAA/Cr) ratio was measured in the thalamus, lenticular nucleus, insular cortex, occipital periventricular white matter, and pons. After 1 year, 19 (44%) patients had unfavorable outcomes (death, persistent vegetative state, or minimally conscious state) and 24 (56%) favorable outcomes (normal consciousness with or without functional impairments). Analysis of variance was performed to compare FA and NAA/Cr in the two outcome groups and controls. FA and MRS findings showed highly significant differences between the outcome groups, with significant variables by LDA being supratentorial FA, NAA/Cr (pons), NAA/Cr (thalamus), NAA/Cr (insula), and infratentorial FA. LDA of combined FA and MRS data clearly separated the unfavorable outcome, favorable outcome, and control groups, with no overlap. Unfavorable outcome was predicted with up to 86% sensitivity and 97% specificity; these values were better than those obtained with DTI or MRS alone. Conclusion: FA and NAA/Cr hold potential as quantitative outcome-prediction tools at the subacute phase of TBI.

Prevention of external ventricular drain – related ventriculitis

SummaryObjective. The purpose of this study was to test if a reduction of external ventricular drains (EVD) related ventriculitis could be achieved by a strict protocol of care and if protocol violation was associated with a higher incidence of EVD-related ventriculitis.Methods. A written protocol for EVD insertion, nursing and surveillance was implemented. A retrospective comparison of EVD-related ventriculitis incidence was performed between control (161 EVD in 131 patients) and study periods (216 EVD in 175 patients). Risk factor analysis was performed in patients in whom an EVD was inserted during the study period including the relationship between protocol compliance and ventriculitis. A score for the number of protocol violations (absence of hair clipping, absence of a tunnelled EVD, absence of shampooing, incorrect dressing change, inappropriate CSF bag or tap samplings and EVD manipulation) was established for each patient.Results. Incidence of patient-related ventriculitis decreased from 12.2% (1999) down to 5.7% (p<0.05) as well as incidence of EVD-related ventriculitis (9.9% vs 4.6%, p<0.05). During the study period, the only statistically significant risk factors for infection were CSF leak and protocol violations. The mean protocol violation score was 4 times higher in the infected versus the non-infected patients (p<0.0001). Patients with a violation score of 0 or 1 had no infection (EVD duration 2 to 42 days).Conclusion. EVD can be left safely, as long as needed, provided that meticulous care is taken for EVD insertion and nursing. EVD duration seems to have no effect on infection incidence.

Dose-response curves of inhaled nitric oxide with and without intravenous almitrine in nitric oxide-responding patients with acute respiratory distress syndrome

Background Inhaled nitric oxide, a selective pulmonary vasodilator, in combination with intravenous almitrine, a selective pulmonary vasoconstrictor, markedly improves arterial oxygenation in 50–60% of patients with acute lung injury. The goal of this study was to assess dose response of inhaled nitric oxide with and without almitrine in patients with acute respiratory distress syndrome responding to nitric oxide.