Respiratory challenges and ventilatory management in different types of acute brain-injured patients.

Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the intensive care unit (ICU). The goal of MV, which is to protect the lung and the brain from further injury, may be difficult to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues and ventilator management, specific to ABI patients in the ICU.

Change in end-tidal carbon dioxide outperforms other surrogates for change in cardiac output during fluid challenge.

Background: During fluid challenge, volume expansion (VE)-induced increase in cardiac output (Δ VE CO) is seldom measured. Methods: In patients with shock undergoing strictly controlled mechanical ventilation and receiving VE, we assessed minimally invasive surrogates for Δ VE CO (by transthoracic echocardiography): fluid-induced increases in end-tidal carbon dioxide (Δ VE E'CO2 ); pulse (Δ VE PP), systolic (Δ VE SBP), and mean systemic blood pressure (Δ VE MBP); and femoral artery Doppler flow (Δ VE FemFlow). In the absence of arrhythmia, fluid-induced decrease in heart rate (Δ VE HR) and in pulse pressure respiratory variation (Δ VE PPV) were also evaluated. Areas under the receiver operating characteristic curves (AUC ROC s) reflect the ability to identify a response to VE (Δ VE CO ≥15%). Results: In 86 patients, Δ VE E'CO2 had an AUC ROC =0.82 [interquartile range 0.73-0.90], significantly higher than the AUC ROC for Δ VE PP, Δ VE SBP, Δ VE MBP, and Δ VE FemFlow (AUC ROC =0.61-0.65, all P <0.05). A value of Δ VE E'CO2 >1 mm Hg (>0.13 kPa) had good positive (5.0 [2.6-9.8]) and fair negative (0.29 [0.2-0.5]) likelihood ratios. The 16 patients with arrhythmia had similar relationships between Δ VE E'CO2 and Δ VE CO to patients with regular rhythm ( r 2 =0.23 in both subgroups). In 60 patients with no arrhythmia, Δ VE E'CO2 (AUC ROC =0.84 [0.72-0.92]) outperformed Δ VE HR (AUC ROC =0.52 [0.39-0.66], P <0.05) and tended to outperform Δ VE PPV (AUC ROC =0.73 [0.60-0.84], P =0.21). In the 45 patients with no arrhythmia and receiving ventilation with tidal volume <8 ml kg -1 , Δ VE E'CO2 performed better than Δ VE PPV, with AUC ROC =0.86 [0.72-0.95] vs 0.66 [0.49-0.80], P =0.02. Conclusions: Δ VE E'CO2 outperformed Δ VE PP, Δ VE SBP, Δ VE MBP, Δ VE FemFlow, and Δ VE HR and, during protective ventilation, arrhythmia, or both, it also outperformed Δ VE PPV. A value of Δ VE E'CO2 >1 mm Hg (>0.13 kPa) indicated a likely response to VE.

Pharmacokinetics of high-dose nebulized amikacin in ventilated critically ill patients.

BACKGROUND: Antibiotic nebulization theoretically allows the delivery of high doses to the lungs together with limited systemic exposure and toxicity. This study aimed to describe amikacin pharmacokinetics, and especially its absorption, in patients treated with high-dose nebulized amikacin. PATIENTS AND METHODS: Twenty critically ill patients experiencing ventilator-associated pneumonia received a 20 mg/kg infusion of amikacin, followed by either three other infusions or three nebulizations of 60 mg/kg amikacin. An extensive sampling regimen allowed measurement of amikacin serum concentrations at 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 24 h after each administration. Amikacin pharmacokinetics was studied by population compartmental modelling. RESULTS: Amikacin pharmacokinetics was best described using a two-compartment structural model with first-order distribution and elimination, in which lung absorption was described using a transit model. Estimated means (interindividual variability) of the main parameters were: bioavailability F = 2.65% (22.1%); transit compartments n = 1.58 (fixed); transit constant ktr = 1.38 h-1 (33.4%); central volume Vc = 10.2 L (10.5%); and elimination constant k10 = 0.488 h-1 (35.8%). The addition of interoccasion variability on F (44.0%) and k10 (41.7%) allowed the description of intraindividual variability of bioavailability and elimination. Amikacin clearance was positively correlated with baseline creatinine clearance. CONCLUSIONS: Our pharmacokinetic model provided an accurate description of amikacin concentrations following nebulization. There was wide interindividual and interoccasion variability in the absorption and elimination of amikacin. Nevertheless, systemic exposure after nebulization was always much lower than after infusion, an observation suggesting that nebulized high doses are safe in this regard and may be used to treat ventilator-associated pneumonia.

Blood pressure monitoring during arrhythmia: agreement between automated brachial cuff and intra-arterial measurements.

BACKGROUND: Since arrhythmia induces irregular pulse waves, it is widely considered to cause flawed oscillometric brachial cuff measurements of blood pressure (BP). However, strong data are lacking. We assessed whether the agreement of oscillometric measurements with intra-arterial measurements is worse during arrhythmia than during regular rhythm. METHODS: Among patients of three intensive care units (ICUs), a prospective comparison of three pairs of intra-arterial and oscillometric BP readings was performed among patients with arrhythmia and an arterial line already present. After each inclusion in the arrhythmia group, one patient with regular rhythm was included as a control. International Organization for Standardization (ISO) standard validation required a mean bias <5 (sd 8) mm Hg. RESULTS: In 135 patients with arrhythmia, the agreement between oscillometric and intra-arterial measurements of systolic, diastolic and mean BP was similar to that observed in 136 patients with regular rhythm: for mean BP, similar mean bias [-0.1 (sd 5.2) and 1.9 (sd 5.9) mm Hg]. In both groups, the ISO standard was satisfied for mean and diastolic BP, but not for systolic BP (sd >10 mm Hg) in our ICU population. The ability of oscillometry to detect hypotension (systolic BP <90 mm Hg or mean BP <65 mm Hg), response to therapy (>10% increase in mean BP after cardiovascular intervention) and hypertension (systolic BP >140 mm Hg) was good and similar during arrhythmia and regular rhythm (respective areas under the receiver operating characteristic curves ranging from 0.89 to 0.96, arrhythmia vs regular rhythm between-group comparisons all associated with P>0.3). CONCLUSIONS: Contrary to widespread belief, arrhythmia did not cause flawed automated brachial cuff measurements.

An evaluation of a new single-use flexible bronchoscope with a large suction channel: reliability of bronchoalveolar lavage in ventilated piglets and initial clinical experience.

A single-use flexible bronchoscope with a large suction channel has become available recently and we have evaluated this innovative device. Firstly, bronchoalveolar lavage was performed and quantified in ventilated piglets. Next, the bronchoscope was evaluated in three intensive care units and a satisfaction questionnaire was carried out. Sixteen bronchoalveolar lavages were performed in piglets with a recovery rate of 83 (79-86 [72-89])% of the instilled volume. Quality and performance of all devices tested was identical. The medical satisfaction questionnaire was as follows: 'acceptable' to 'very good' for quality of aspiration, manoeuvrability and quality of vision; 'very good' to 'perfect' for setting up and insertion. This encouraging preliminary evaluation demonstrates the effectiveness of this new single-use device, which may obviate the need for disinfection procedures and, thereby, eradicate a potential vector of patient cross-contamination.

In vitro - in vivo correlation of intranasal drug deposition.

In vitro - in vivo correlation (IVIVC) allows prediction of in vivo drug deposition from a nasally inhaled drug based on in vitro drug measurements. In vitro measurements include physical particle characterization and, more recently, deposition studies using anatomical models. Currently, there is a lack of IVIVC for deposition measurements in anatomical models, especially for deposition patterns in various nasal cavity regions. Therefore, improvement of in vitro and in vivo measurement methods and knowledge about nasal deposition mechanisms should help IVIVC in the future.

[Post-intensive care syndrome]. / Le syndrome post-réanimation.

Post-intensive care syndrome is an entity defined in 2010 and covering any sequelae following an extended hospitalization in intensive care unit. It comprises psychological, cognitive and physical disorders (neuromyopathy, respiratory dysfunction, joint stiffness, among others). These sequelae have important consequences on autonomy and quality of life of these patients, as well as on their healthcare consumption and on mortality. Psychological sequelae can also be seen in hospitalized patients' relatives. Screening and management of these disorders is more and more frequent but no method has formally proven effective. The number of patients surviving an intensive care unit hospitalization is increasing, and management of post-intensive care syndrome is a major issue. It seems important that the internist be aware of this syndrome, given his pivotal role in global management of patients and frequent implication into care after the intensive care unit.

[Use of the intraosseous access in adult patients in France in 2012]. / Utilisation de la voie intraosseuse chez l'adulte en France en 2012.

OBJECTIVES: To evaluate theoretical and practical knowledges of intraosseous (IO) access in adults patients in France in 2012. STUDY DESIGN: National observational descriptive transversal study as survey of opinion and practices. MATERIALS AND METHODS: An email, with an URL to online computerized quiz, was sent to residents and medical doctors who were working, in France, in anesthesiologist units, intensive care units or emergency units. Several questions were asked about theoretical and practical knowledges concerning IO access. RESULTS: After 1359 responses, 396 (29%) practitioners have used an IO kit mainly in case of cardiopulmonary arrest in adults (68%). The insurance of operators in this technique and the rate of physicians who has even put an IO catheter increased with the years of experience of physicians. The reasons given for not using an IO access were no trouble placing a peripheral vein (77%) and unfamiliarity with the equipment and technology (32%). Most of practitioners (753 [55%]) have been trained and 90% (n=265) of untrained doctors believe that training was necessary. The powered system was the most used (71%). CONCLUSION: Only 29% of practitioners have ever used an IO kit. With the new IO kits, a theoretical and practical training is needed to ensure IO kit used.

[Influence of pressure- and volume-controlled ventilation on pulse pressure variations: randomized study]. / Influence du mode de ventilation sur la variation respiratoire de la pression pulsée artérielle: étude randomisée.

OBJECTIVE: Pulse pressure variation (ΔPP) has been demonstrated to be an accurate dynamic parameter to predict fluid responsiveness. However, the impact of different ventilator modes on this parameter is unknown. We compared ΔPP values calculated alternatively during pressure- and volume-controlled ventilation. STUDY DESIGN: Double-blind randomized study, cross-over design. PATIENTS: Patients in intensive care unit after a cardiac surgery. METHOD: Patients were ventilated alternatively in both ventilator modes (according to the randomization): volume-controlled ventilation (VVC) and pressure-controlled ventilation (VPC). Other parameters of ventilation were identical. ΔPP values were calculated for each patient in both ventilator modes. RESULTS: Among the 26 patients analyzed, mean ΔPP value was de 14.0±7.3% in VVC and 11.8±6.2% in VPC (P<0,0001). On Bland-Altman representation, mean bias was +2.2±2.3% and inferior and superior limits of agreement were respectively -2.3 and 6.7%. Arterial blood pressure and central venous pressure were not modified. CONCLUSION: ΔPP values obtained with both ventilator modes were not interchangeable. On average, ΔPP decreases by more than two points in the passage VVC to VPC for a given patient, all others things being equal.

Brachial cuff measurements of blood pressure during passive leg raising for fluid responsiveness prediction.

OBJECTIVE: The passive leg raising maneuver (PLR) for fluid responsiveness testing relies on cardiac output (CO) measurements or invasive measurements of arterial pressure (AP) whereas the initial hemodynamic management during shock is often based solely on brachial cuff measurements. We assessed PLR-induced changes in noninvasive oscillometric readings to predict fluid responsiveness. STUDY DESIGN: Multicentre interventional study. PATIENTS AND METHODS: In ICU sedated patients with circulatory failure, AP (invasive and noninvasive readings) and CO measurements were performed before, during PLR (trunk supine, not modified) and after 500-mL volume expansion. Areas under the ROC curves (AUC) were determined for fluid responsiveness (>10% volume expansion-induced increase in CO) prediction. RESULTS: In 112 patients (19% with arrhythmia), changes in noninvasive systolic AP during PLR (noninvasiveΔ(PLR)SAP) only predicted fluid responsiveness (cutoff 17%, n=21, positive likelihood ratio [LR] of 26 [18-38]), not unresponsiveness. If PLR-induced change in central venous pressure (CVP) was at least of 2 mm Hg (n=60), suggesting that PLR succeeded in altering cardiac preload, noninvasiveΔ(PLR)SAP performance was good: AUC of 0.94 [0.85-0.98], positive and negative LRs of 5.7 [4.6-6.8] and 0.07 [0.009-0.5], respectively, for a cutoff of 9%. Of note, invasive AP-derived indices did not outperform noninvasiveΔ(PLR)SAP. CONCLUSION: Regardless of CVP (i.e., during "blind PLR"), noninvasiveΔ(PLR)SAP more than 17% reliably identified fluid responders. During "CVP-guided PLR", in case of sufficient change in CVP, noninvasiveΔ(PLR)SAP performed better (cutoff of 9%). These findings, in sedated patients who had already undergone volume expansion and/or catecholamines, have to be verified during the early phase of circulatory failure (before an arterial line and/or a CO measuring device is placed).

Polymorphism in the 5' flanking region of the bovinelactoglobulin-encoding gene and its association with ß-lactoglobulin in the milk.

SUMMARY: Genomic DNA of 71 cows was analysed with the help of polymerase-chain-reaction-based restriction fragment length polymorphisms of five DNA variants within the 5' flanking region (R1, R2, R3, R5, and R14 at positions +31, +27, -22, -209, -662 bp from transcription start point +1) of the bovine ß-lactoglobulin (ß-Lg) encoding gene. Protein variants, content and yield of ß-Lg were determined in milk samples of each cow. Frequencies of the common alleles varied between 0.52 and 1.0 per breed. One of three different genotype combinations (BB/AA/AA/AA/AA/AA, AB/AB/AB/AA/AB/AB, and AA/BB/BB/AA/BB/BB for ß-Lg-variant/R1/R2/R3/R5/R14) was carried by 82% of the cows, so that in populations two haplotypes at a similar frequency can be assumed. Associations between variants in the ß-Lg-encoding gene, and yield as well as content of ß-Lg, were obtained for cows of the genotypes BB/AA/AA/AA/AA/AA, AB/AB/AB/AA/AB/AB, and AA/BB/BB/AA/BB/BB (least square-means ± SE): 91.8 ± 6.9 g/day and 10.78 ± 0.61%, 140.5 ± 10.7 g/day and 13.94 ± 0.86%, and 149.4 ± 8.2 g/day and 17.59 ± 0.65% respectively. Differences were p < 0.001. The population data can be explained by the effects of the gene variants on regulation of the expression of the corresponding gene. ZUSAMMENFASSUNG: Polymorphismen in der 5' flankierenden Region des bovinen ß-Lactoglobulin codierenden Gens and deren Beziehungen zum ß-Lactoglobulin in der Milch Genomische DNA von 71 Kühen wurde mit Hilfe der PCR-Technik und nachfolgender Darstellung von RFLPs auf fünf DNA-Varianten (R1, R2, R3, R5 und R14 an den Positionen +31, +27, -22, -209, -662 bp vom Transkriptions-Startpunkt +1) innerhalb der 5' flankierenden Region des bovinen ß-Lactoglobulin(ß-Lg)-codierenden Gens untersucht. Proteinvarianten, -gehalt und -menge wurden für das ß-Lg aus Milchproben einzelner Kühe bestimmt. Die Frequenzen der häufigen Allele variierten swischen 0, 52 und 1, 0 pro Rasse. 82% der Kühe trugen eine von drei verschiedenen Genotypkombinationen (BB/AA/AA/AA/AA/AA, AB/AB/AB/AA/AB/AB und AA/BB/BB/AA/BB/BB für die ß-Lg-Variante/R1/R2/R3/R5/R14), so daß in den Populationen zwei Haplotypen in ähnlichen Frequenzen angenommen werden können. Beziehungen zwischen Varianten in dem ß-Lg-codierenden Gen und der Menge sowie dem Gehalt an ß-Lg waren für Kühe mit den Genotypen BB/AA/AA/AA/AA/AA, AB/AB/AB/AA/AB/AB und AA/BB/BB/AA/BB/BB: 91, 8 ± 6, 9 g/d und 10, 78 ± 0.61%, 140, 5 ± 10, 7 g/d und 13.94 ± 0.86%, bzw. 149, 4 ± 8.2 g/d und 17, 59 ± 0, 64%. Die Differenzen waren signifikant (p < 0, 001). Aus den Populationsdaten lassen sich Effekte der Genvarianten auf die Expressionsregulation der betreffenden Gene annehmen.

Quantification of gene effects on single milk proteins in selected groups of dairy cows.

SUMMARY: Different alleles and genotypes per polymorphic milk protein were compared, within the concentration and quantity of the protein which is coded from the corresponding locus. Cows were chosen according to their diversity in milk-protein content, as well as in the polymorphic milk proteins. Polymorphic milk proteins were analysed by isoelectric focusing. The contents and quantities of total milk protein and whey protein were measured photometrically. Single milk proteins were quantified after poly-acrylamide gel electrophoresis, using computer-assisted densitometer. The contents of single milk proteins could be measured with repeatabilities between 0.58 (α-lactalbumin) and 0.97 (ß-lactoglobulin). Close associations were observed between alleles/genotypes of milk-protein-coding gene loci, and the contents, as well as the yields, of the corresponding milk proteins, Superior alleles concerned with the content yield of corresponding proteins have been ß-lactoglobulin A, α(s1) -casein C, and ß-casein B. Simultaneous comparison of genotypes of the casein gene cluster with the milk-protein values revealed significant effects through distinct allele combinations. Breed influences on the associations between genes and milk proteins were considerably smaller than the influences from single milk-protein-coding loci. Intragenic haplotypes may explain the associations between variants in coding DNA sequences and gene expression, estimated for single milk proteins. An analysis of balancing forces on allele frequencies and haplotype combinations per population will be necessary, before genotype screening can be applied usefully for breeding. ZUSAMMENFASSUNG: Quantifizierung von Geneffekten auf einzelne Milchproteine in selektierten Milchkuh-Gruppen Verschiedene Allele und Genotypen pro polymorphes Milchprotein wurden mit der Konzentration und Menge des Proteins verglichen, das vom betreffenden Locus kodiert wird. Zu diesem Zweck wurden Kühe aufgrund des Proteingehaltes in der Milch sowie der Unterschiedlichkeit in den polymorphen Milchproteinen ausgewählt. Die polymorphen Milchproteine wurden mittels Isoelektrischer Fokussierung dargestellt. Die Gehalte und Mengen des gesamten Milchproteins und des Molkenproteins wurden photometrisch gemessen. Unter Verwendung eines Rechner-unterstützten Densitometers wurden die einzelnen Michproteine nach Elektrophorese in Polyacrylamidgelen quantifiziert. Die Gehalte der einzelnen Milchproteine konnten mit Wiederholbarkeiten zwischen 0,58 (α-Lactalbumin) und 0,97 (ß-Lactoglobulin) gemessen werden. Zwischen Allelen/Genotypen der Milchprotein-codierenden Genloci and den Gehalten wie auch den Mengen der korrespondierenden Michproteine ließen sich enge Assoziationen beobachten. Die im Hinblick auf Gehalt/Menge des betreffenden Proteins überlegenen Allele waren ß-Lactoglobulin A, α(s1) -Casein C and ß-Casein B. Ein simultaner Vergleich der Genotypen des Casein-Genclusters zeigte signifikante Assoziationen der Milchproteinwerte mit bestimmten Allelkom-binationen. Rasseneinflüsse auf die Assoziationen zwischen Genen und Milchproteinen waren deutlich kleiner als die Einflüsse durch einzelne Milchprotein-codierende Loci. Die gefundenen Assoziationen zwischen Varianten in codierenden DNA-Sequenzen und der Expression einzelner Milchproteine können durch intragene Haplotypen erklärt werden. Analysen der balanzierenden Kräfte auf die Allelfrequenzen und Haplotyp-Kombinationen pro Population sind notwendig, bevor ein Genotypen-Screening in der Züchtung mit Vorteil angewendet werden kann.