Prospective validation of a new airway management algorithm and predictive features of intubation difficulty.

BACKGROUND: Some patients have features that indicate possible difficulty with direct laryngoscopy for tracheal intubation. Prediction of the likely outcome and selection of patients for an enhanced management algorithm would reduce the possible harm from failed intubation attempts. METHODS: Adult elective patients were assessed for seven features associated with difficult direct laryngoscopy, ranked in difficulty from 0 to 3. For a patient with at least one Class 3 feature, or two or more features of class 1 or higher, the enhanced management used a channelled videolaryngoscope Airtraq™ instead of a Macintosh laryngoscope. A long flexible angulated stylet and a flexible fibrescope would be used as the second and third steps. For patients with lesser difficulty scores, a Macintosh laryngoscope was used. Outcomes of enhanced management were analysed. Logistic regression and Random Forest algorithm, using the ranks of the predictive features, were used to predict difficulty during enhanced management. RESULTS: We prospectively studied 16 695 patients. We selected 1501 (9%) for enhanced management, and tracheal intubation was successful in all of them. Of these, 73% were intubated in less than 30 s, and only 4.5% required more than 4 min for intubation. Progression to the second and third steps of enhanced management was predicted by restriction of mouth opening and reduced cervical spine mobility. CONCLUSIONS: An enhanced management algorithm allowed successful tracheal intubation of all patients with anticipated difficult laryngoscopy. The need to combine the use of a stylet and a fibrescope with the Airtraq™ could be predicted with a high degree of certainty.

Coagulase-negative staphylococci are associated to the mild inflammatory pattern of healthcare-associated meningitis: a retrospective study.

The epidemiology of healthcare-associated meningitis (HAM) is dominated by commensal bacteria from the skin, as coagulase-negative staphylococci (CoNS). We hypothesized that the pauci-symptomatic and mild inflammatory patterns of HAM are related to the low pathogenic state of CoNS. Our aim was to describe clinical and biological features of CoNS HAM, compared to other HAM. All consecutive patients with HAM admitted in our hospital were retrospectively included from 2007 to 2014. HAM due to CoNS were compared to HAM caused by other bacteria (controls) for clinical and laboratory patterns. Seventy-one cases of HAM were included, comprising 18 CoNS and 53 controls. Patients were not different in terms of baseline characteristics. CoNS HAM occurred later after the last surgery than controls (17 vs. 12 days, p = 0.029) and had higher Glasgow Coma Scale (GCS) score (14 vs. 13, p = 0.038). Cerebrospinal fluid (CSF) analysis revealed a lower pleocytosis (25 vs. 1340/mm3, p < 0.001), a higher glucose level (3.75 vs. 0.8 mmol/L, p < 0.001), and a lower protein level (744 vs. 1751 mg/L, p < 0.001) in the CoNS group than in the control group, respectively. HAM due to CoNS was significantly less symptomatic and less inflammatory than HAM due to other bacteria.

Study of prone positioning to reduce ventilator-associated pneumonia in hypoxaemic patients.

The aim of the present study was to examine whether prone positioning (PP) affects ventilator associated-pneumonia (VAP) and mortality in patients with acute lung injury/adult respiratory distress syndrome. 2,409 prospectively included patients were admitted over 9 yrs (2000-2008) to 12 French intensive care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction ratios <300 during the first 48 h. Controls were matched to PP patients on the PP propensity score (+/-10%), MV duration longer than that in PP patients before the first turn prone, and centre. VAP incidence was similar in the PP and control groups (24 versus 13 episodes.1,000 patient-days MV(-1) respectively, p = 0.14). After adjustment, PP did not decrease VAP occurrence (HR 1.64 (95% CI 0.70-3.84); p = 0.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39-0.79); p = 0.001), without decreasing 28-day mortality (37% in both groups). Post hoc analyses indicated that PP did not protect against VAP but, when used for >1 day, might decrease mortality and benefit the sickest patients (Simplified Acute Physiology Score >50). In ICU patients with hypoxaemic acute respiratory failure, PP had no effect on the risk of VAP. PP delayed mortality without decreasing 28-day mortality. PP >1 day might decrease mortality, particularly in the sickest patients.

AMP-activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives.

As the liver is central in the maintenance of glucose homeostasis and energy storage, knowledge of the physiology as well as physiopathology of hepatic energy metabolism is a prerequisite to our understanding of whole-body metabolism. Hepatic fuel metabolism changes considerably depending on physiological circumstances (fed vs. fasted state). In consequence, hepatic carbohydrate, lipid and protein synthesis/utilization are tightly regulated according to needs. Fatty liver and hepatic insulin resistance (both frequently associated with the metabolic syndrome) or increased hepatic glucose production (as observed in type 2 diabetes) resulted from alterations in substrates oxidation/storage balance in the liver. Because AMP-activated protein kinase (AMPK) is considered as a cellular energy sensor, it is important to gain understanding of the mechanism by which hepatic AMPK coordinates hepatic energy metabolism. AMPK has been implicated as a key regulator of physiological energy dynamics by limiting anabolic pathways (to prevent further ATP consumption) and by facilitating catabolic pathways (to increase ATP generation). Activation of hepatic AMPK leads to increased fatty acid oxidation and simultaneously inhibition of hepatic lipogenesis, cholesterol synthesis and glucose production. In addition to a short-term effect on specific enzymes, AMPK also modulates the transcription of genes involved in lipogenesis and mitochondrial biogenesis. The identification of AMPK targets in hepatic metabolism should be useful in developing treatments to reverse metabolic abnormalities of type 2 diabetes and the metabolic syndrome.

Effects of acute hypoxic exposure on prooxidant/antioxidant balance in elite endurance athletes.

We investigated whether acute hypoxic exposures could modify the pro-oxidant/antioxidant balance in elite endurance athletes, known to have efficient antioxidant status. Forty-one elite athletes were subjected to two hypoxic tests: one at an altitude of 4 800 m during 10-min of mild exercise (4 800 m test) and the second at rest for 3 h at an altitude of 3 000 m (3 000 m test). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric reducing antioxidant power (FRAP) and lipid-soluble antioxidants were measured before and immediately after the 4 800 m test and at the end of the 3 000 m test. The 4 800 m and the 3 000 m tests induced a significant increase in the level of MDA and AOPP (+7.1% and +71.7% for 4 800 m test and +8.6% and +40.9% for 3 000 m test). The changes in plasma MDA and arterial oxygen saturations were significantly correlated (r=0.35) during the 3 000 m test. FRAP values (-13%) and alpha-tocopherol (-21%) were decreased following the 3 000 m test. However, following the 4 800 m test, only alpha-tocopherol was decreased (-16%). These results provide evidence that the highly-trained athletes do not have the antioxidant buffering capacity to counterbalance free radical over-production generated by acute hypoxic exposure, with or without mild exercise.

Effects of the 'live high-train low' method on prooxidant/antioxidant balance on elite athletes.

BACKGROUND/OBJECTIVES: We previously demonstrated that acute exposure to hypoxia (3 h at 3000 m) increased oxidative stress markers. Thus, by using the 'living high-training low' (LHTL) method, we further hypothesized that intermittent hypoxia associated with endurance training alters the prooxidant/antioxidant balance. SUBJECTS/METHODS: Twelve elite athletes from the Athletic French Federation were subjected to 18-day endurance training. They were divided into two groups: one group (control group) trained at 1200 m and lived in hypoxia (2500-3000 m simulated altitude) and the second group trained and lived at 1200 m. The subjects performed an acute hypoxic test (10 min at 4800 m) before and immediately after the training. Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA), ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants normalized for triacylglycerols, and cholesterol and retinol were measured before and after the 4800 m tests. RESULTS: After the training, MDA and AOPP concentrations were decreased in response to the 4800 m test only for the control group. Eighteen days of LHTL induced a significant decrease of all antioxidant markers (FRAP, P=0.01; alpha-tocopherol, P=0.04; beta-carotene, P=0.01 and lycopene, P=0.02) for the runners. This imbalance between antioxidant and prooxidant might result from insufficient intakes in vitamins A and E. CONCLUSIONS: The LHTL model characterized by the association of aerobic exercises and intermittent resting hypoxia exposures decreased the antioxidant status whereas the normoxic endurance training induced preconditioning mechanisms in response to the 4800 m test.

Energy expenditure of submaximal running does not increase after cycle-run transition.

AIM: This study was performed to determine the relationship between increased fat oxidation and decreased running efficiency following intense cycling exercise. METHODS: Twenty-two middle-level triathletes were studied during submaximal running before and after submaximal cycling exercise. All subjects completed a 13-min run on a track at a velocity corresponding to 75% of their maximal aerobic speed (MAS) before (T1) and after (T2) submaximal cycling exercise at 75 % of maximal aerobic power (MAP). The energy cost of running (Cr) was quantified using the O(2) uptake (.VO(2)) and energy expenditure (EE) using the respiratory exchange ratio (RER). Gas exchange was measured over 30 s during the 3(rd) min and last 30 s of each run. RESULTS: The results show that after cardiorespiratory equilibration (12 min 30 s), Cr (calculated in mL(O(2))*kg(-1)*m(-1)) during T2 was higher than during T1 (+ 8.2+/-4.3%; P = 0.03). Similar observations were made for .VO(2) (+ 8.2+/-4.3%; P = 0.03) and pulmonary ventilation (+ 7.0+/-12.3%; P = 0.04). RER decreased between T1 and T2 (- 8.6+/-9.2 %; p = 0.01). EE and Cr expressed in kJ.kg(-1).m(-1) did not vary significantly between T1 and T2. CONCLUSION: We suggest that the decrease in RER drop may be a result of greater lipid oxidation as metabolic substrate after cycling exercise.

[An acute respiratory distress syndrome revealing a chronic eosinophilic pneumonia]. / Un syndrome de détresse respiratoire aiguë inaugural d'une pneumopathie chronique idiopathique à éosinophiles.

Idiopathic chronic eosinophilic pneumonia (ICEP) is one of the idiopathic hypereosinophilic lung diseases. ICEP differs from idiopathic acute eosinophilic pneumonia (IAEP) by its progressive onset, and the absence of severe hypoxemia. We report a case of acute respiratory distress syndrome revealing an ICEP, which needed a 48h of mechanical ventilation. ICEP is an exceptional cause of acute respiratory failure. Symptoms always improve with corticosteroids. But relapses are frequent after stopping corticosteroid treatment, as well as the occurrence of severe asthma. Distinction between ICEP and IAEP is essential because of its impact on treatment duration and on prognosis.

Targeting AMP-activated protein kinase as a novel therapeutic approach for the treatment of metabolic disorders.

In the light of recent studies in humans and rodents, AMP-activated protein kinase (AMPK), a phylogenetically conserved serine/threonine protein kinase, has been described as an integrator of regulatory signals monitoring systemic and cellular energy status. AMP-activated protein kinase (AMPK) has been proposed to function as a 'fuel gauge' to monitor cellular energy status in response to nutritional environmental variations. Recently, it has been proposed that AMPK could provide a link in metabolic defects underlying progression to the metabolic syndrome. AMPK is a heterotrimeric enzyme complex consisting of a catalytic subunit alpha and two regulatory subunits beta and gamma. AMPK is activated by rising AMP and falling ATP. AMP activates the system by binding to the gamma subunit that triggers phosphorylation of the catalytic alpha subunit by the upstream kinases LKB1 and CaMKKbeta (calmodulin-dependent protein kinase kinase). AMPK system is a regulator of energy balance that, once activated by low energy status, switches on ATP-producing catabolic pathways (such as fatty acid oxidation and glycolysis), and switches off ATP-consuming anabolic pathways (such as lipogenesis), both by short-term effect on phosphorylation of regulatory proteins and by long-term effect on gene expression. As well as acting at the level of the individual cell, the system also regulates food intake and energy expenditure at the whole body level, in particular by mediating the effects of insulin sensitizing adipokines leptin and adiponectin. AMPK is robustly activated during skeletal muscle contraction and myocardial ischaemia playing a role in glucose transport and fatty acid oxidation. In liver, activation of AMPK results in enhanced fatty acid oxidation as well as decreased glucose production. Moreover, the AMPK system is one of the probable targets for the anti-diabetic drugs biguanides and thiazolidinediones. Thus, the relationship between AMPK activation and beneficial metabolic effects provide the rationale for the development of new therapeutic strategies in metabolic disorders.

Effects of exercise and training in hypoxia on antioxidant/pro-oxidant balance.

OBJECTIVE: The aim was to investigate the effects of acute exercise under hypoxic condition and the repetition of such exercise in a 'living low-training high' training on the antioxidant/prooxidant balance. DESIGN: Randomized, repeated measures design. SETTING: Faculté de Médecine, Clermont-Ferrand, France. SUBJECTS: Fourteen runners were randomly divided into two groups. A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. INTERVENTION: A 6-week endurance training protocol integrated two running sessions per week at the second ventilatory threshold into the usual training. The first hypoxic group (HG, n=8) carried out these sessions under hypoxia (3000 m simulated altitude) and the second normoxic group (NG, n=6) in normoxia. In control period, the runners were submitted to two incremental cycling tests performed in normoxia and under hypoxia (simulated altitude of 3000 m). Plasma levels of advanced oxidation protein products (AOPP), malondialdehydes (MDA) and lipid oxidizability, ferric-reducing antioxidant power (FRAP), lipid-soluble antioxidants (alpha-tocopherol and beta-carotene) normalized for triacyglycerols and cholesterol were measured before and after the two incremental tests and at rest before and after training. RESULTS: No significant changes of MDA and AOPP level were observed after normoxic exercise, whereas hypoxic exercise induced a 56% rise of MDA and a 44% rise of AOPP. Plasma level of MDA and arterial oxygen hemoglobin desaturations after the acute both exercises were highly correlated (r=0.73). alpha-Tocopherol normalized for cholesterol and triacyglycerols increased only after hypoxic exercise (10-12%, P<0.01). After training, FRAP resting values (-21%, P<0.05) and alpha-tocopherol/triacyglycerols ratio (-24%, P<0.05) were diminished for HG, whereas NG values remained unchanged. CONCLUSIONS: Intense exercise and hypoxia exposure may have a cumulative effect on oxidative stress. As a consequence, the repetition of such exercise characterizing the 'living low-training high' model has weakened the antioxidant capacities of the athletes. SPONSORSHIP: International Olympic Committee and the Direction Régionale de la Jeunesse et des Sports de la Région Auvergne.

Effect of hypervolemia on heart rate during 4 days of prolonged exercises.

The aim was to evaluate the cardiodynamic adjustment during 4 days of prolonged exercises and to check if the plasma volume (PV) expansion which is observed generally during such events plays a role in this adaptation. Thirteen subjects exercised 5 hours per day on a cycle ergometer alternately with a treadmill for 4 days (D1 to D4) (6 x 50 min sessions per day). The individual cycle ergometer load and the treadmill speed were unchanged during each exercise session and throughout all the sessions, and corresponded to a moderate exercise intensity: 58 - 63 % of peak oxygen uptake (VO (2)peak). Heart rate (HR) was recorded every 15 s during each exercise session and VO (2) was measured from the expired air at the beginning and the end of each exercise session. Relative PV changes were measured from haematocrit and haemoglobin changes in the morning before the exercise bouts. No significant changes of VO (2) were observed between the first and the last exercise session i. e. for cycling: 2.1 +/- 0.2 l/min and for running: 2.4 +/- 0.3 l/min. Between the first and the last day, HR decreased from 143 to 129 bpm for cycle (p < 0.0001) and from 147 to 137 bpm (p = 0.01) for treadmill. As compared to D1, PV increased gradually from D2 (+ 1.8 % +/- 4.7 %) to D4 (+ 8.5 % +/- 4.7 %). The individual PV increases were significantly correlated with cycling HR decreases from D1 to D4 (r (2) = 0.40, p = 0.02). In conclusion, the 4 days' prolonged exercise induced a HR decrease during submaximal exercise without VO (2) drift. Here we suggested that this HR decline could be in part linked to the transient PV expansion.