Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial.

PURPOSE: Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation. METHODS: A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48 h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality. RESULTS: In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48 h was 67.2 vs. 63.3 % (P = 0.66), the asynchrony index was 14.7 vs. 26.7 % (P < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0-4.0] vs. 0.0 days [0.0-1.0] (P < 0.01), the ventilator-free days at day 28 were 21 days [4-25] vs. 17 days [0-23] (P = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % (P = 0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6 % (P < 0.01). CONCLUSIONS: NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient-ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02018666.

Complex mode of inheritance in holoprosencephaly revealed by whole exome sequencing.

Holoprosencephaly (HPE) is the most common congenital cerebral malformation, characterized by impaired forebrain cleavage and midline facial anomalies. Heterozygous mutations in 14 genes have been associated with HPE and are often inherited from an unaffected parent, underlying complex genetic bases. It is now emerging that HPE may result from a combination of multiple genetic events, rather than from a single heterozygous mutation. To explore this hypothesis, we undertook whole exome sequencing and targeted high-throughput sequencing approaches to identify mutations in HPE subjects. Here, we report two HPE families in which two mutations are implicated in the disease. In the first family presenting two foetuses with alobar and semi-lobar HPE, we found mutations in two genes involved in HPE, SHH and DISP1, inherited respectively from the father and the mother. The second reported case is a family with a 9-year-old girl presenting lobar HPE, harbouring two compound heterozygous mutations in DISP1. Together, these cases of digenic inheritance and autosomal recessive HPE suggest that in some families, several genetic events are necessary to cause HPE. This study highlights the complexity of HPE inheritance and has to be taken into account by clinicians to improve HPE genetic counselling.

Effect of flumazenil on diaphragm electrical activation during weaning from mechanical ventilation after acute respiratory distress syndrome.

BACKGROUND: Diaphragm electrical activation (EAdi) and the ratio of tidal volume to EAdi (VT/EAdi) may provide clinical information on neuroventilatory efficiency (NVE) in patients being weaned from mechanical ventilation. We tested the hypothesis that residual sedation could interfere with respiratory recovery, by assessing the effects of flumazenil on EAdi and VT/EAdi ratio. METHODS: This observational study included 13 patients breathing with pressure-support ventilation (PSV) after a long period of controlled mechanical ventilation (i.e. >4 days) plus midazolam-based sedation for acute respiratory distress syndrome. EAdi and respiratory patterns were compared before and after a bolus of flumazenil, which was given because neurological status needed to be evaluated. RESULTS: Flumazenil induced a significant increase in EAdi [+71 (41-123)%, P=0.0002] and VT [+17 (8-32)%, P=0.0005], resulting in significantly decreased NVE [-34 (15-43)%]. The increased VT was significantly correlated with the increased EAdi (ρ=0.70, P=0.009). CONCLUSIONS: During weaning from mechanical ventilation, the diaphragmatic contribution to the breathing process may be reduced by residual midazolam-induced ventilatory depression. The increased EAdi with reversal of residual sedation was associated with a proportional increase in VT. These findings should be considered by the attending physician when interpreting daily EAdi and VT changes during weaning from mechanical ventilation.

Intraoperative management of heart-lung interactions: "from hypothetical prediction to improved titration".

Extensive literature describes the suitability of dynamic parameters to predict responsiveness in fluid. However, based on heart-lung interactions, these parameters can have serious limitations, including the use of protective lung ventilation. Although the latter seems to be beneficial for healthy patients undergoing high-risk surgery, the intraoperative interpretation of dynamic parameters to predict fluid responsiveness can be hazardous. In this context, the attending physician could, alternatively, titrate the need of fluids with a small fluid challenge, which remains unaffected by low tidal volume, the presence of arrhythmia, or the presence of spontaneous ventilation. When intraoperative prediction of fluid responsiveness is required in mechanically ventilated patients, "improved" titration should be preferred to a hypothetical prediction.

Extracorporeal membrane oxygenation in adults for severe acute respiratory failure.

The purpose of this review is to examine the indications of extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). This technique of oxygenation has significantly increased worldwide with the H1N1 flu pandemic. The goal of ECMO is to maintain a safe level of oxygenation and controlled respiratory acidosis under protective ventilation. The enthusiasm for ECMO should not obscure the consideration for potential associated complications. Before widespread diffusion of ECMO, new trials should test the efficacy of early initiation or CO2 removal in addition to, or even as an alternative to mechanical ventilation for severe ARDS.

Neuro-ventilatory efficiency during weaning from mechanical ventilation using neurally adjusted ventilatory assist.

BACKGROUND: Neuro-ventilatory efficiency (NVE), defined as the tidal volume to electrical diaphragm-activity ratio (VT/EAdi) at the beginning and end of the weaning process after acute hypoxaemic respiratory failure, may provide valuable information about patient recovery. METHODS: This observational study included 12 patients breathing with neurally adjusted ventilatory assist (NAVA). When a spontaneous breathing trial (SBT) with pressure support of 7 cm H2O and PEEP was unsuccessful, NAVA was used and the level was adjusted to obtain an EAdi of ∼60% of maximal EAdi during SBT. VT and EAdi were recorded continuously. We compared changes in NVE between NAVA and SBT at the first failed and first successful SBT. RESULTS: When patients were switched from NAVA to SBT, NVE was significantly reduced during both unsuccessful and successful SBT (-56 and -38%, respectively); however, this reduction was significantly lower when SBT was successful (P=0.01). Between the first and last day of weaning, we observed that NVE decreased with NAVA [40.6 (27.7-89.5) vs 28.8 (18.6-46.7); P=0.002] with a significant decrease in NAVA level, whereas it remained unchanged during SBT [15.4 (10.7-39.1) vs 19.5 (11.6-29.6); P=0.50] with significant increases in both EAdi and VT and no difference in respiratory rhythm. CONCLUSIONS: These results suggest that in patients after respiratory failure and prolonged mechanical ventilation, changes in VT and NVE, between SBTs are indicative of patient recovery. Larger clinical trials are needed to clarify whether changes in NVE reliably predict weaning in patients ventilated with NAVA.

[Changes in kaliemia following rapid sequence induction with succinylcholine in critically ill patients]. / Variation de kaliémie après une induction en séquence rapide avec la succinylcholine chez les patients de réanimation.

OBJECTIVE: Evaluate the changes in potassium following rapid sequence induction with succinylcholine in critically ill-patients and determine whether hospital length of stay could influence the succinylcholine-induced hyperkaliemia. STUDY DESIGN: Prospective and observational study. PATIENTS AND METHODS: After approval by our local ethical committee, we prospectively included 36 patients admitted from more than 24hours in ICU and who required succinylcholine for rapid tracheal intubation (1mg/kg). Serum potassium was measured before, 5 and 30min after succinylcholine. The incidence of life-threatening hyperkaliemia (≥6.5mmol/L) was noted. RESULTS: We could observe significant and transient increase in serum potassium (median increase of 0.45 [0.20-0.80] mmol/L at five minutes). A significant relationship was observed between the ICU length of stay and arterial potassium increase (r=0.37, P<0.05). From the ROC curve, a threshold of 12 days had an 86% sensitivity and 69% specificity in discriminating patients in whom the potassium increase was more than 1.5mmol/L. CONCLUSION: Induction with succinylcholine is followed by significant but transient hyperkaliema. The ICU length of stay before giving succinylcholine could influence significantly the amplitude of potassium increase.

[Place of traditional CBP in bipulmonary transplantation]. / Place de la CEC traditionnelle en transplantation bipulmonaire.

Initially double-lung transplantation (DLT) was performed with airway anastomosis at the tracheal bifurcation requiring a cardiopulmonary bypass (CBP). Complications related to ischemia of the bronchi and trachea around the carina prompted adoption of sequential single lung implantations as the method of choice for DLT. In different studies, CPB was associated with an increase in postoperative morbidity but this was probably due to the selection of more severe patients. Moreover, important progress in the technology of CPB has occurred. Therefore, the systematic use of CPB during sequential lung transplantation might have some interest by limiting the occurrence of ventilation and perfusion injuries. This article discusses the potential beneficial effects of CPB during double-lung transplantation.

Reducing tidal volume and increasing positive end-expiratory pressure with constant plateau pressure during one-lung ventilation: effect on oxygenation.

BACKGROUND: It is no longer safe to use large tidal volumes (V(T)) (>8 ml kg(-1)) for one-lung ventilation (OLV), and limiting plateau pressure should be a major objective. Due to the specificity of OLV, the use of positive end-expiratory pressure (PEEP) remains controversial. This study determined whether at the same low plateau pressure, reducing V(T) and increasing PEEP were not inferior to larger V(T) and lower PEEP ventilation in terms of oxygenation. METHODS: This prospective, randomized, non-inferiority, cross-over trial included 88 patients undergoing open thoracotomy who received two successive ventilatory strategies in random order: V(T) (8 ml kg(-1) of ideal body weight) with low PEEP (5 cm H(2)O), or low V(T) (5 ml kg(-1)) with a high PEEP. Respiratory rate and PEEP were, respectively, adjusted to maintain constant ventilation and plateau pressure. The primary endpoint was the ratio under each ventilatory strategy. RESULTS: The non-inferiority of low-V(T) ventilation could not be established. The mean adjusted ratio was lower overall during low-V(T) ventilation, and differences between the two ventilatory modes varied significantly according to baseline (T0). Decreased oxygenation during low V(T) was smaller when baseline values were low. Systolic arterial pressure was not lower during low-V(T) ventilation. CONCLUSION: During OLV, lowering V(T) and increasing PEEP, with the same low plateau pressure, reduced oxygenation compared with larger V(T) and lower PEEP. This strategy may reduce the risk of lung injury, but needs to be investigated further.

Pandemic influenza A(H1N1) 2009: molecular characterisation and duration of viral shedding in intensive care patients in Bordeaux, south-west France, May 2009 to January 2010.

From May 2009 to January 2010, the Virology Laboratory at the University Hospital of Bordeaux received more than 4,000 nasopharyngeal samples from the Aquitaine region (south-west France) for the diagnosis of pandemic influenza A(H1N1)2009. Eighty-three infected patients deteriorated and were admitted to intensive care units. Our study focused on 24 of these patients. Positivity for influenza A(H1N1)2009 was monitored by realtime PCR and duration of viral shedding was determined. The first available sample of each patient was analysed for bacterial, fungal and viral co-infection. We observed six bacterial (or bacterial/fungal) co-infections and one viral co-infection with respiratory syncytial virus. The samples were analysed for the presence of the neuraminidase H275Y (N1 numbering) mutation, which confers resistance to oseltamivir, by realtime PCR of the neuraminidase gene. No H275Y mutation was observed in any of the viral strains screened in this study. In parallel, a fragment of the haemagglutinin gene encoding amino acid residues 173 to 362 was sequenced to detect mutations that had been reported to increase the severity of the disease. Two patients were infected by strains bearing the D222G (H3 numbering) mutation. The viral shedding of A(H1N1)2009 in this study ranged from four to 28 days with a median of 11 days.

[Severe H1N1 2009 influenza infection in adults: the French experience]. / Formes graves de la grippe H1N1 2009 chez l'adulte: l'expérience française.

The REVA-Flu-SRLF register allowed collection of data from 562 patients infected with H1N1 influenza virus 2009 and hospitalized in the intensive care unit (ICU). The overall mortality of these patients was 20%. The use of invasive ventilation, heart failure, and immunosuppression were associated with mortality. Three hundred forty-one (82%) among the 417 mechanically ventilated patients had an acute respiratory distress syndrome (ARDS). One hundred sixty-nine (30%) had a bacterial co-infection. Corticosteroid therapy was associated with an increased mortality in patients with ARDS. The occupancy rate associated with influenza patients crossed the threshold of 15% in many ICUs.

Pressure-controlled ventilation and intrabronchial pressure during one-lung ventilation.

BACKGROUND: Pressure-controlled ventilation (PCV) has been suggested to reduce peak airway pressure (P(peak)) and intrapulmonary shunt during one-lung ventilation (OLV) when compared with volume-controlled ventilation (VCV). At the same tidal volume (V(T)), the apparent difference in P(peak) is mainly related to the presence of a double-lumen tracheal tube. We tested the hypothesis that the decrease in P(peak) observed in the breathing circuit is not necessarily associated with a decrease in the bronchus of the dependent lung. METHODS: This observational study included 15 consecutive subjects who were ventilated with VCV followed by PCV at constant V(T). Airway pressure was measured simultaneously in the breathing circuit and main bronchus of the dependent lung after 20 min of ventilation. RESULTS: PCV induced a significant decrease in P(peak) [mean (sd)] measured in the breathing circuit [36 (4) to 26 (3) cm H(2)0, P<0.0001] and in the bronchus [23 (4) to 22 (3) cm H(2)O, P=0.01]. However, the interaction (ventilatory mode x site of measurement) revealed that the decrease in P(peak) was significantly higher in the circuit (P<0.0001). Although the mean percentage decrease in P(peak) was significant at both sites, the decrease was significantly lower in the bronchus [5 (6)% vs 29 (3)%, P<0.0001]. CONCLUSIONS: During PCV for OLV, the decrease in P(peak) is observed mainly in the respiratory circuit and is probably not clinically relevant in the bronchus of the dependent lung. This challenges the common clinical perception that PCV offers an advantage over VCV during OLV by reducing bronchial P(peak).

[Stomach rupture associated with noninvasive ventilation]. / Rupture gastrique au décours d'une séance de ventilation non invasive.

Noninvasive positive-pressure ventilation (NIPPV) is a safe method to treat acute respiratory failure and is known to decrease the need for intubation and the length of ICU-stay. Few severe complications have been reported even when the indications are respected. Some rare cases of gastric distension were recently described. We report the case of a gastric perforation associated with NIPPV. The treatment was closure with a primary interrupted two-layer suture. Recovery was complete and the patient was transferred to the ward on Day 11.

[Effectiveness of a recruitment manoeuvre and positive end-expiratory pressure on respiratory mechanics during laparoscopic bariatric surgery]. / Efficacité d'une manoeuvre de recrutement alvéolaire associée à une pression expiratoire positive sur la mécanique respiratoire en coeliochirurgie bariatrique.

OBJECTIVE: To evaluate recruitment manoeuvre (RM) efficiency associated with a 10 cmH(2)O positive end expiratory pressure (PEEP) on respiratory mechanic estimated by lung compliance (Ctp) and PEEP to ZEEP expiratory volume delta (Delta VTE) during laparoscopic bariatric surgery in patients with morbid obesity. STUDY DESIGN: Prospective randomized study. METHODS: Twenty-six obese patients (BMI>40 kg/m(2)) undergoing laparoscopic bariatric surgery. The recruitment group received an RM followed by a 10 cmH(2)O PEP versus only 10 cmH(2)O PEP in the control group. Ctp was measured during the intervention and functional residual capacity (FRC) was estimated measuring Delta VTE during a PEP to ZEP manoeuvre. Mann and Whitney tests as well as a t-test were used (significance p<0.05). RESULTS: In the RM group, a significant improvement of 52+/-14 ml/cmH(2)O was noted versus a 36+/-10 ml/cmH(2)O in the PEP group (p=0,004). This improvement was transitory and no statistically significant Delta VTE difference was noted between the groups at the end of the intervention (360 [90-770]ml [MRA] and 310 [190-450]ml [PEP]). CONCLUSION: In patients with morbid obesity undergoing laparoscopic bariatric surgery, an RM conducted prior the pneumoperitoneum temporarily improves lung mechanics but without any change of the end expiratory lung volume at the end of the surgery in comparison with PEP alone. The RM was well tolerated.