Gerald Chanques

Rapidly Progressive Diaphragmatic Weakness and Injury during Mechanical Ventilation in Humans

RATIONALE Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans. OBJECTIVES To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena. METHODS Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-κB, and calpains). MEASUREMENTS AND MAIN RESULTS TwPtr decreased progressively during MV, with a mean reduction of 32 ± 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 ± 4.8 vs. 4.7 ± 0.6% area), decreased cross-sectional area of muscle fibers (1,904 ± 220 vs. 3,100 ± 329 μm²), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-κB (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm. CONCLUSIONS Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.

Difficult intubation in obese patients: incidence, risk factors, and complications in the operating theatre and in intensive care units

BACKGROUND Intubation procedure in obese patients is a challenging issue both in the intensive care unit (ICU) and in the operating theatre (OT). The objectives of the study were (i) to compare the incidence of difficult intubation and (ii) its related complications in obese patients admitted to ICU and OT. METHODS We conducted a multicentre prospective observational cohort study in ICU and OT in obese (BMI≥30 kg m(-2)) patients. The primary endpoint was the incidence of difficult intubation. Secondary endpoints were the risk factors for difficult intubation, the use of difficult airway management techniques, and severe life-threatening complications related to intubation (death, cardiac arrest, severe hypoxaemia, severe cardiovascular collapse). RESULTS In cohorts of 1400 and 11 035 consecutive patients intubated in ICU and in the OT, 282 (20%) and 2103 (19%) were obese. In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT (16.3% vs 8.2%, P<0.01). In both cohorts, risk factors for difficult intubation were Mallampati score III/IV, obstructive sleep apnoea syndrome, and reduced mobility of cervical spine, while limited mouth opening, severe hypoxaemia, and coma appeared only in ICU. Specific difficult airway management techniques were used in 66 (36%) cases of difficult intubation in obese patients in the OT and in 10 (22%) cases in ICU (P=0.04). Severe life-threatening complications were significantly more frequent in ICU than in the OT (41.1% vs 1.9%, relative risk 21.6, 95% confidence interval 15.4-30.3, P<0.01). CONCLUSIONS In obese patients, the incidence of difficult intubation was twice more frequent in ICU than in the OT and severe life-threatening complications related to intubation occurred 20-fold more often in ICU. CLINICAL TRIAL REGISTRATION Current controlled trials. Identifier: NCT01532063.

Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial

IMPORTANCE It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery. OBJECTIVE To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure <60 mm Hg or oxygen saturation [SpO2] ≤90% when breathing room air or <80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure. INTERVENTIONS Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain SpO2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain SpO2 ≥94%) (n = 148). MAIN OUTCOMES AND MEASURES The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation-free days at day 30, health care-associated infections, and 90-day mortality. RESULTS Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, -12.4%; 95% CI, -23.5% to -1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation-free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, -2.2 days; 95% CI, -0.1 to 4.6 days; P = .04), while fewer patients developed health care-associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, -17.8%; 95% CI, -30.2% to -5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, -6.5%; 95% CI, -16.0% to 3.0%; P = .15). There were no significant differences in gas exchange. CONCLUSIONS AND RELEVANCE Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01971892.

Feasibility and Effectiveness of Prone Position in Morbidly Obese Patients With ARDS: A Case-Control Clinical Study

BACKGROUND Obese patients are at risk for developing atelectasis and ARDS. Prone position (PP) may reduce atelectasis, and it improves oxygenation and outcome in severe hypoxemic patients with ARDS, but little is known about its effect in obese patients with ARDS. METHODS Morbidly obese patients (BMI ≥ 35 kg/m²) with ARDS (Pao₂/FIo₂ ratio ≤ 200 mm Hg) were matched to nonobese (BMI < 30 kg/m²) patients with ARDS in a case-control clinical study. The primary end points were safety and complications of PP; the secondary end points were the effect on oxygenation (Pao₂/FIo₂ ratio at the end of PP), length of mechanical ventilation and ICU stay, nosocomial infections, and mortality. RESULTS Between January 2005 and December 2009, 149 patients were admitted for ARDS. Thirty-three obese patients were matched with 33 nonobese patients. Median (25th-75th percentile) PP duration was 9 h (6-11 h) in obese patients and 8 h (7-12 h) in nonobese patients (P = .28). We collected 51 complications: 25 in obese and 26 in nonobese patients. The number of patients with at least one complication was similar across groups (n = 10, 30%). Pao₂/FIo₂ ratio increased significantly more in obese patients (from 118 ± 43 mm Hg to 222 ± 84 mm Hg) than in nonobese patients (from 113 ± 43 mm Hg to 174 ± 80 mm Hg; P = .03). Length of mechanical ventilation, ICU stay, and nosocomial infections did not differ significantly, but mortality at 90 days was significantly lower in obese patients (27% vs 48%, P < .05). CONCLUSIONS PP seems safe in obese patients and may improve oxygenation more than in nonobese patients. Obese patients could be a subgroup of patients with ARDS who may benefit the most of PP.

Moderate and prolonged hypercapnic acidosis may protect against ventilator-induced diaphragmatic dysfunction in healthy piglet: an in vivo study

IntroductionProtective ventilation by using limited airway pressures and ventilation may result in moderate and prolonged hypercapnic acidosis, as often observed in critically ill patients. Because allowing moderate and prolonged hypercapnia may be considered protective measure for the lungs, we hypothesized that moderate and prolonged hypercapnic acidosis may protect the diaphragm against ventilator-induced diaphragmatic dysfunction (VIDD). The aim of our study was to evaluate the effects of moderate and prolonged (72 hours of mechanical ventilation) hypercapnic acidosis on in vivo diaphragmatic function.MethodsTwo groups of anesthetized piglets were ventilated during a 72-hour period. Piglets were assigned to the Normocapnia group (n = 6), ventilated in normocapnia, or to the Hypercapnia group (n = 6), ventilated with moderate hypercapnic acidosis (PaCO2 from 55 to 70 mm Hg) during the 72-hour period of the study. Every 12 hours, we measured transdiaphragmatic pressure (Pdi) after bilateral, supramaximal transjugular stimulation of the two phrenic nerves to assess in vivo diaphragmatic contractile force. Pressure/frequency curves were drawn after stimulation from 20 to 120 Hz of the phrenic nerves. The protocol was approved by our institutional animal-care committee.ResultsModerate and prolonged hypercapnic acidosis was well tolerated during the study period. The baseline pressure/frequency curves of the two groups were not significantly different (Pdi at 20 Hz, 32.7 ± 8.7 cm H2O, versus 34.4 ± 8.4 cm H2O; and at 120 Hz, 56.8 ± 8.7 cm H2O versus 60.8 ± 5.7 cm H2O, for Normocapnia and Hypercapnia groups, respectively). After 72 hours of ventilation, Pdi decreased by 25% of its baseline value in the Normocapnia group, whereas Pdi did not decrease in the Hypercapnia group.ConclusionsModerate and prolonged hypercapnic acidosis limited the occurrence of VIDD during controlled mechanical ventilation in a healthy piglet model. Consequences of moderate and prolonged hypercapnic acidosis should be better explored with further studies before being tested on patients.

Effects of etomidate on complications related to intubation and on mortality in septic shock patients treated with hydrocortisone: a propensity score analysis

IntroductionEndotracheal intubation in the ICU is associated with a high incidence of complications. Etomidate use is debated in septic shock because it increases the risk of critical illness-related corticosteroid insufficiency, which may impact outcome. We hypothesized that hydrocortisone, administered in all septic shock cases in our ICU, may counteract some negative effects of etomidate.The aim of our study was to compare septic shock patients who received etomidate versus another induction drug both for short-term safety and for long-term outcomes.MethodsA single-center observational study was carried out in septic shock patients, treated with hydrocortisone and intubated within the first 48 hours of septic shock. Co-primary end points were life-threatening complications incidence occurring within the first hour after intubation and mortality during the ICU stay. Statistical analyses included unmatched and matched cohorts using a propensity score analysis. P < 0.05 was considered significant.ResultsSixty patients in the etomidate cohort and 42 patients in the non-etomidate cohort were included. Critical illness-related corticosteroid insufficiency was 79% in the etomidate cohort and 52% in the non-etomidate cohort (P = 0.01). After intubation, life-threatening complications occurred in 36% of the patients whatever the cohort. After adjustment with propensity score analysis, etomidate was a protective factor for death in the ICU both in unmatched (hazard ratio, 0.33 (0.15 to 0.75); P < 0.01)) and matched cohorts (hazard ratio, 0.33 (0.112 to 0.988); P = 0.04).ConclusionIn septic shock patients treated with hydrocortisone, etomidate did not decrease life-threatening complications following intubation, but when associated with hydrocortisone it also did not impair outcome.

La sédation–analgésie au quotidien : enquête de pratiques auprès de 218 services de réanimation en France

OBJECTIVES To assess the current use of sedation and analgesia in a large sample of French intensive care units (ICUs) and to define structural characteristics of the units that use a written procedure. STUDY DESIGN Self-reported survey. PARTICIPANTS Three hundred and sixty French ICUs were presented the questionnaire in September 2007. RESULTS Surveys were received from 228 (60.6%) ICUs. Midazolam was used in more than 50% of the patients in 79.2% of the ICUs and propofol in 22.2% of the ICUs. Sufentanil was the most frequently used morphinic. A sedation-scale was used in 68.8% of the units (80.3% Ramsay score). Sedation was assessed at least every 4hours in 61% of ICUs. A pain-scale was used in 88.9% of the ICUs, but only 12.5% in the non-communicant patients. A written procedure was used in 29.4% of the units only. In multivariate analysis, use in the ICU of a written procedure for the early management of patients with septic shock and/or intensive insulin therapy was the single variable significantly associated with presence of a written procedure for sedation and analgesia (respectively OR 4.37; p<0.0001 and OR 5.64; p=0.032). CONCLUSION Although more than two-third of the responding ICUs reported the use of sedation-and-pain-scales, frequency of assessment was low, and objective assessment of pain in the non-communicating patients was extremely uncommon. Similarly, the use of written procedure was low. The use of sedation-analgesia written procedure in an ICU seems strongly influenced by a more global involvement of the ICU in the protocolisation of complex care. These findings support the reinforcement of educational programs.

Obesity and Mortality in Critically Ill Patients: Another Case of the Simpson Paradox?

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L’archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d’enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Obesity and mortality in critically ill patients: another case of the simpson paradox? Audrey de Jong, Boris Jung, Gerald Chanques, Samir Jaber, Nicolas Molinari

Mechanical Ventilation in Obese ICU Patients: From Intubation to Extubation

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Épidémiologie, pronostic et complications infectieuses nosocomiales des pancréatites aiguës graves en réanimation : étude prospective multicentrique à partir de la base de données CClin Sud-Est

OBJECTIVES To describe the demographic characteristics, incidence of extra-abdominal hospital-acquired infections and outcome of patients admitted to intensive care unit (ICU) with severe acute pancreatitis. STUDY DESIGN A retrospective, observational multiple center (65 centers) analysis of prospectively acquired data. PATIENTS AND METHODS During 2 years, all consecutive admitted patients to ICU for severe acute pancreatitis in the centers participating in the nosocomial infections surveillance network CClin Sud-Est were included. Patients whose ICU stay was less than 48 hours were not included. Demographic characteristics, extra-abdominal hospital-acquired infections and clinical course were described. RESULTS During the study period, 510 patients were included which represented 2 % of patients with a length of stay longer than 48 hours in the 65 participating ICUs. The global attack rate of extra-abdominal hospital-acquired infections (pneumonia, bacteremia, urinary tract or central venous catheter infection) was 23 % in overall patients and it was 33 % in the 294 mechanically ventilated patients. ICU mortality was 20 % in overall patients and it was 34 % in mechanically ventilated patients. CONCLUSION Severe acute pancreatitis represents 2 % of ICU stay longer than 48 hours. Its clinical course is frequently complicated by hospital-acquired infections and is associated with an high ICU mortality rate. This epidemiological observational study may be used for calculating sample size for future multicenter interventional therapeutic studies.