读书报告 ICM and AJRCCM 7-9

梁冠林

Systematic Review Noninvasive ventilation in chest trauma: systematic review and meta-analysis

These results suggest that NIV could be useful in the management of acute respiratory failure due to chest trauma.

Prognostic value of troponins in sepsis: a meta-analysis Elevated troponin identifies a subset of patients with sepsis at higher risk of death.

Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM EEG monitoring is an important diagnostic tool for specific indications. Further

data are necessary to understand its potential for ischemia assessment and coma prognostication

Optimal sedation in pediatric intensive care patients: a systematic review Oversedation is more common than undersedation. As oversedation may lead to

longer hospitalization, tolerance, and withdrawal, preventing oversedation in pediatric intensive care deserves greater attention.

Clinical impact of arterial ammonia levels in ICU patients with different liver diseases

Purpose Increased arterial ammonia levels are associated with high mortality in patients with acute liver failure

(ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis.

Methods The patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis

and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group.

Results Overall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30,

49 and 27 %, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (p < 0.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (p < 0.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (p < 0.01), ALF (p < 0.05) and cirrhosis (p < 0.05), respectively.

Conclusions Elevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with

advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.

Systemic inflammatory response syndrome criteria and vancomycin dose requirement in patients with sepsis

Purpose Vancomycin has been used in patients with sepsis infected by MRSA and shows large interindividual

variability in its dosing. In this observational study the potential influence of sepsis status on the vancomycin dose requirement in relation to systemic inflammatory response syndrome (SIRS) criteria was assessed.

Methods From about 250 patients receiving serum vancomycin monitoring from May 2006 to April 2011 at the

Osaka National Hospital, 105 adult patients who had been assessed using the SIRS criteria were identified. Patients on chemotherapy or intermittent positive pressure ventilation in whom the SIRS criteria could not accurately evaluate inflammatory status were excluded. Using two vancomycin serum concentrations at peak and trough, individual pharmacokinetic parameters were calculated by the Bayesian estimation method using a two-compartment model. Creatinine clearance rate was estimated by the Cockcroft-Gault formula (eCcr).

Results Patients with SIRS had a significantly higher vancomycin clearance than those without SIRS, indicating

that SIRS patients had a higher elimination capacity. The vancomycin clearance was positively correlated with the SIRS score defined as the number of positive items in the criteria, and negatively with age, except in patients with renal dysfunction. A linear relationship between the vancomycin clearance and eCcr remained even in the supernormal eCcr phase (more than approximately 120 mL/min).

Conclusions This study provides a new insight into the need for quick prediction of dose requirement. That is, an

increased vancomycin dosage would be needed in patients with a higher SIRS score to maintain the therapeutic target concentration, in particular in those with a high eCcr value.

Risk factors for carbapenem-resistant Gram-negative bacteremia in intensive care unit patients

Purpose Carbapenem-resistant (CR) Gram-negative pathogens have increased substantially. This study was

performed to identify the risk factors for development of CR Gram-negative bacteremia (GNB) in intensive care unit (ICU) patients.

Methods Prospective study; risk factors for development of CR-GNB were investigated using two groups of case

patients: the first group consisted of patients who acquired carbapenem susceptible (CS) GNB and the second group included patients with CR-GNB. Both case groups were compared to a shared control group defined as patients without bacteremia, hospitalized in the ICU during the same period.

Results Eighty-five patients with CR- and 84 patients with CS-GNB were compared to 630 control patients,

without bacteremia. Presence of VAP (OR 7.59, 95 % CI 4.54–12.69, p < 0.001) and additional intravascular devices (OR 3.69, 95 % CI 2.20–6.20, p < 0.001) were independently associated with CR-GNB. Presence of VAP (OR 2.93, 95 % CI 1.74–4.93, p < 0.001), presence of additional intravascular devices (OR 2.10, 95 % CI 1.23–3.60, p = 0.007) and SOFA score on ICU admission (OR 1.11, 95 % CI 1.03–1.20, p = 0.006) were independently associated with CS-GNB. The duration of exposure to carbapenems (OR 1.079, 95 % CI 1.022–1.139, p = 0.006) and colistin (OR 1.113, 95 % CI 1.046–1.184, p = 0.001) were independent risk factors for acquisition of CR-GNB. When the source of bacteremia was other than VAP, previous administration of carbapenems was the only factor related with the development of CR-GNB (OR 1.086, 95 % CI 1.003–1.177, p = 0.042).

Conclusions Among ICU patients, VAP development and the presence of additional intravascular devices were the

major risk factors for CR-GNB. In the absence of VAP, prior use of carbapenems was the only factor independently related to carbapenem resistance.

Changes in the mean systemic filling pressure during a fluid challenge in postsurgical intensive care patients

Purpose The difference between mean systemic filling (Pmsf) and central venous pressure (CVP) is the venous

return gradient (dVR). The aim of this study is to assess the significance of the Pmsf analogue (Pmsa) and the dVR during a fluid challenge.

Methods We performed a prospective observational study in postsurgical patients. Patients were monitored with a

central venous catheter, a LiDCO™plus and the Navigator™. A 250-ml intravenous fluid challenge was given over 5 min. A positive response to the fluid challenge was defined as either a stroke volume (SV) or cardiac output increase of greater than 10 %.

Results A total of 101 fluid challenges were observed in 39 patients. In 43 events (42.6 %) the SV and CO

increased by more than 10 %. Pmsa increased similarly during a fluid challenge in responders and non-responders (3.1 ± 1.9 vs. 3.1 ± 1.8, p = 0.9), whereas the dVR increased in responders (1.16 ± 0.8 vs. 0.2 ± 1, p < 0.001) as among non-responders CVP increased along with Pmsa (2.9 ± 1.7 vs. 3.1 ± 1.8, p = 0.15). Resistance to venous return did not change immediately after a fluid challenge. Heart performance (Eh) decreased significantly among non-responders (0.41 ± 0.15 vs. 0.34 ± 0.13, p < 0.001) whereas among responders it did not change when compared with baseline value (0.35 ± 0.15 vs. 0.34 ± 0.12, p = 0.15).

Conclusions The changes in Pmsa and dVR measured at the bedside during a fluid challenge are consistent with the

cardiovascular model described by Guyton.

Early diffusion-weighted magnetic resonance imaging in children after cardiac arrest may provide valuable

prognostic information on clinical outcome Objective We examined whether early diffusion-weighted magnetic resonance imaging (DW-MRI) abnormalities of

the brain and variation of apparent diffusion coefficient (ADC) values can provide prognostic information on clinical outcome in children following cardiac arrest (CA).

Design Retrospective study. Setting A 12-bed paediatric intensive care unit (PICU). Patients Children aged between 1 month and 18 years who had DW-MRI with ADC measurement within the first

week following CA. Neurological outcomes were assessed using the Pediatric Cerebral Performance Category Scale (PCPC). Differences between the favourable (PCPC ≤3) and unfavourable (PCPC ≥4) groups were analysed with regard to clinical data, electrophysiological patterns as well as qualitative and quantitative DW-MRI abnormalities.

Results Twenty children with a median age of 20 months (1.5–185) and a male/female sex ratio of 1.5 underwent

DW-MRI after CA with a median delay of 3 days (1–7). Aetiologies of CA were (i) asphyxia (n = 10), (ii) haemodynamic (n = 5) or (iii) unknown (n = 5). With regard to DW-MRI findings, the unfavourable outcome group (n = 8) was associated with cerebral cortex (p = 0.02) and basal ganglia (p = 0.005) lesions, with a larger number of injured brain regions (p = 0.001) and a global decrease in measured ADC signal (p = 0.008). Normal DW-MRI (n = 5) was exclusively associated with the favourable outcome group (n = 12).

Conclusion Qualitative, topographic and quantitative analysis of early DW-MRI with ADC measurement in children

following CA may provide valuable prognostic information on neurological outcomes.

Correlation of thermodilution-derived extravascular lung water and ventilation/perfusion-compartments in a

porcine model Purpose This study examines the correlation between the transpulmonary thermodilution derived

extravascular lung water content (EVLW) and the ventilation/perfusion-distribution () measured by multiple inert gas elimination (MIGET) in a porcine model.

Methods measured by micropore membrane inlet mass spectrometry-MIGET (MMIMS-MIGET) and

EVLW were simultaneously measured in twelve pigs in the heathy state, with impaired gas exchange from repetitive lung lavage and after 3 h of ventilation. The relationship between compartments and EVLW was analysed by linear correlation and regression.

Results Considerable increases in EVLW and mismatching were induced through the lavage

procedure. Significant correlations between the EVLW and the fractions representing pulmonary shunt and low were found. Perfusion to the normal regions was inversely correlated to the EVLW.

Conclusions Increased EVLW is associated with increased low and shunt, but not equal to pulmonary

shunt alone. Beneath true shunt EVLW can also be associated with low regions.

Decreased respiratory rate variability during mechanical ventilation is associated with increased mortality

Objective Patients on ventilatory support often experience significant changes in respiratory rate. Our aim was to

determine the possible association between respiratory rate variability (RRV) and outcomes in these patients.

Design A longitudinal, prospective, observational study of patients mechanically ventilated for at least 12 h

performed in a medical-surgical intensive care unit. Patients were enrolled within 24 h of the initiation of ventilatory support. We measured airway signals continuously for the duration of ventilatory support and calculated expiratory flow frequency spectra at 2.5-min intervals. We assessed RRV using the amplitude ratio of the flow spectrum’s first harmonic to the zero frequency component. Measures of the amplitude ratio were averaged over the total monitored time. Patients with time-averaged amplitude ratios <40 % were classified as high RRV and those ≥40 % as low RRV. All-cause mortality rates were assessed at 28 and 180 days from enrollment with a Cox proportional hazards model adjusted for disease acuity by the simplified acute physiology score II.

Results We enrolled 178 patients, of whom 47 had high RRV and 131 low RRV. Both groups had similar disease

acuity upon enrollment. The 28- and 180-day mortality rates were greater for low RRV patients with hazard ratios of 4.81 (95 % CI 1.85–12.65, p = 0.001) and 2.26 (95 % CI 1.21–4.20, p = 0.01), respectively. Independent predictors of 28-day mortality were low RRV, i.v. vasopressin, and SAPS II.

Conclusions Decreased RRV during ventilatory support is associated with increased mortality. The mechanisms

responsible for this finding remain to be determined.

Dyspnea and surface inspiratory electromyograms in mechanically ventilated patients

Context Pressure support ventilation (PSV) must be tailored to the load capacity balance of the respiratory system.

While "over assistance" generated hyperinflation and ineffective efforts, "under assistance" increased respiratory drive and causes dyspnea. Surface electromyograms (sEMGs) of extradiaphragmatic inspiratory muscles were responsive to respiratory loading/unloading.

Objectives To determine if sEMGs of extradiaphragmatic inspiratory muscles vary with PSV settings and relate to the degree of discomfort and the intensity of dyspnea in acutely ill patients.

Design Pathophysiological study, prospective inclusions of 12 intubated adult patients. Interventions Two PSV levels (high and low) and two expiratory trigger (ET) levels (high and low). Measurements Surface electromyograms of the scalene, parasternal, and Alae Nasi muscles (peak,

EMGmax; area under the curve, EMGAUC); dyspnea visual analogue scale (VAS); prevalence of ineffective triggering efforts.

Main results For the three recorded muscles, EMGmax and EMGAUC were significantly greater with low PS than high PS. The influence of ET was less important. A strong correlation was found between dyspnea and EMGmax. A significant inverse correlation was found between the prevalence of ineffective efforts and both dyspnea-VAS and EMGmin.

Conclusions Surface electromyograms of extradiaphragmatic inspiratory muscles provides a simple, reliable and non-

invasive indicator of respiratory muscle loading/unloading in mechanically ventilated patients. Because this EMG activity is strongly correlated to the intensity of dyspnea, it could be used as a surrogate of respiratory sensations in mechanically ventilated patients, and might, therefore, provide a monitoring tool in patients in whom detection and quantification of dyspnea is complex if not impossible.

Time to reach a new steady state after changes of positive end expiratory pressure

Purpose To assess the time interval required to reach a new steady state of oxygenation-, ventilation-, respiratory

mechanics- and hemodynamics-related variables after decreasing/increasing positive end expiratory pressure (PEEP).

Methods In 23 patients (group 1) with acute respiratory distress syndrome (ARDS), PEEP was decreased from 10 to

5 cmH2O and, after 60′, it was increased from 5 to 15 cmH2O. In 21 other ARDS patients (group 2), PEEP was increased from 10 to 15 cmH2O and, after 60′, decreased from 15 to 5 cmH2O. Oxygenation, ventilation, respiratory mechanics and hemodynamic variables were recorded at time 5′, 15′, 30′ and 60′ after each PEEP change.

Results When PEEP was decreased, PaO2, PaO2/FiO2, venous admixture and arterial oxygen saturation reached

their equilibrium after 5′. In contrast, when PEEP was increased, the equilibrium was not reached even after 60′. The ventilation-related variables did not change significantly with PEEP. The respiratory system compliance, when PEEP was decreased, significantly worsened only after 60′. Hemodynamics did not change significantly with PEEP. In the individual patients the change of oxygenation-related variables and of respiratory system compliance observed after 5′ could predict the changes recorded after 60′. This was not possible for PaCO2.

Conclusions We could not find a unique equilibration time for all the considered variables. However, in general, a

decremental PEEP test requires far lower equilibrium time than an incremental PEEP test, suggesting a different time course for derecruitment and recruitment patterns.

The effect of secular trends and specialist neurocritical care on mortality for patients with intracerebral haemorrhage, myasthenia

gravis and Guillain–Barré syndrome admitted to critical care

Purpose To analyse mortality for spontaneous intracerebral haemorrhage (ICH), myasthenia gravis (MG) and

Guillain–Barré syndrome (GBS) from 1996 to 2009 in UK intensive care units (ICUs). Methods We used the Intensive Care National Audit & Research Centre (ICNARC) database. We identified

specialised neurosciences critical care units (NCCUs) (n = 16), general ICUs with full neurological support (n = 48) and general ICUs with limited neurological support (n = 138) and undertook descriptive analyses for each condition. Poisson regression was used to identify trends in admission rates, median regression to identify trends in lengths of stay (LOS), and logistic regression (Wald test) to analyse interaction between unit type and time period; odds ratios were calculated for hospital mortality associated with unit types.

Results For ICH (n = 10,313 cases), overall ICU mortality was 42.4 %, and acute hospital mortality 62.1 %. In

NCCU, LOS was longer, but mortality lower, and over time, mortality from ICH decreased faster. For MG (n = 1,064 cases) and GBS (n = 1,906 cases), overall mortality was relatively high (MG: 8.7 % ICU mortality and 22 % acute hospital mortality; GBS: 7.7 and 16.7 %, respectively); overall mortality did not decrease over time.

Conclusions This first large-scale analysis of outcomes in acute neurological disease in the UK demonstrates real-life

mortality higher than published series. NCCU care is associated with increased survival in conditions requiring highly specialised intensive care techniques, but high-quality step-down care is pivotal in others. Strategies that truly improve outcomes must integrate emergency department management, ICU admission criteria, NCCU treatment, high-quality step-down care and neurorehabilitation.

Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured

patients: a randomized controlled trial Purpose Preventive treatments of traumatic intracranial hypertension are not yet established. We aimed to compare

the efficiency of half-molar sodium lactate (SL) versus saline serum solutions in preventing episodes of raised intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI).

Methods This was a double-blind, randomized controlled trial including 60 patients with severe TBI requiring ICP

monitoring. Patients were randomly allocated to receive a 48-h continuous infusion at 0.5 ml/kg/h of either SL (SL group) or isotonic saline solution (control group) within the first 12 h post-trauma. Serial measurements of ICP, as well as fluid, sodium, and chloride balance were performed over the 48-h study period. The primary outcome was the number of raised ICP (≥20 mmHg) requiring a specific treatment.

Results Raised ICP episodes were reduced in the SL group as compared to the control group within the 48-h study

period: 23 versus 53 episodes, respectively (p < 0.05). The proportion of patients presenting raised ICP episodes was smaller in the SL group than in the saline group: 11 (36 %) versus 20 patients (66 %) (p < 0.05). Cumulative 48-h fluid and chloride balances were reduced in the SL group compared to the control group (both p < 0.01).

Conclusion A 48-h infusion of SL decreased the occurrence of raised ICP episodes in patients with severe TBI, while

reducing fluid and chloride balances. These findings suggest that SL solution could be considered as an alternative treatment to prevent raised ICP following severe TBI.

Epidemiology and outcome of thrombocytopenic patients in the intensive care unit: results of a prospective

multicenter study Purpose To assess the epidemiology of intensive care unit (ICU) patients with thrombocytopenia (TP). Methods All consecutive ICU-admitted patients with TP either on admission or acquired during ICU stay were

included. TP was defined as either absolute (platelet count <100 × 109/L) or relative (decrease in the platelet count >30 %). Extensive diagnostic workup of TP including bone marrow aspiration was performed.

Results Absolute TP was diagnosed in 208 patients and relative TP in 93. In six patients (2 %), no cause of TP was

identified. The median number of TP etiologies per patient was two, with sepsis being the leading cause. Bone marrow aspirates were analyzed in 238 patients. They showed a normal megakaryocyte number in 221 (93 %) and provided novel information for diagnosis in 52 (22 %). Results were susceptible to having an impact on patient management in 22 cases (11 %). The frequency of bone marrow aspiration with results susceptible to having an impact on management did not differ between patients with and without DIC (P = 0.22) and with and without sepsis/septic shock (P = 0.7) but was significantly lower in patients with relative TP than in those with absolute TP (P < 0.01). A serious bleeding event was observed in 30 patients (14.9 %) and a nadir platelet count below 50 × 109/L was an independent risk factor (P < 0.05).

Conclusions In thrombocytopenic patients, sepsis is the leading cause of TP. Bone marrow aspirates may yield

significant information on TP mechanisms and contribute to the subsequent management of patients, especially those with absolute TP.

High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE

study): a multicentre randomized controlled trial Purpose Septic shock is a leading cause of death among critically ill patients, in particular when complicated by

acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI.

Methods This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in

France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period.

Results Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients

because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups.

Conclusions In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary

SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.

The ETHICA study (part I): elderly’s thoughts about intensive care unit admission for life-sustaining

treatments Purpose To assess preferences among individuals aged ≥80 years for a future hypothetical critical illness requiring

life-sustaining treatments. Methods Observational cohort study of consecutive community-dwelling elderly individuals previously hospitalised

in medical or surgical wards and of volunteers residing in nursing homes or assisted-living facilities. The participants were interviewed at their place of residence after viewing films of scenarios involving the use of non-invasive mechanical ventilation (NIV), invasive mechanical ventilation (IMV), and renal replacement therapy after a period of invasive mechanical ventilation (RRT after IMV). Demographic, clinical, and quality-of-life data were collected. Participants chose among four responses regarding life-sustaining treatments: consent, refusal, no opinion, and letting the physicians decide.

Results The sample size was 115 and the response rate 87 %. Mean participant age was 84.8 ± 3.5 years, 68 %

were female, and 81 % and 71 % were independent for instrumental activities and activities of daily living, respectively. Refusal rates among the elderly were 27 % for NIV, 43 % for IMV, and 63 % for RRT (after IMV). Demographic characteristics associated with refusal were married status for NIV [relative risk (RR), 2.9; 95 % confidence interval (95 %CI), 1.5–5.8; p = 0.002] and female gender for IMV (RR, 2.4; 95 %CI, 1.2–4.5; p = 0.01) and RRT (after IMV) (RR, 2.7; 95 %CI, 1.4–5.2; p = 0.004). Quality of life was associated with choices regarding all three life-sustaining treatments.

Conclusions Independent elderly individuals were rather reluctant to accept life-sustaining treatments, especially IMV

and RRT (after IMV). Their quality of life was among the determinants of their choices.

The ETHICA study (part II): simulation study of determinants and variability of ICU physician decisions

in patients aged 80 or over Purpose To assess physician decisions about ICU admission for life-sustaining treatments (LSTs). Methods Observational simulation study of physician decisions for patients aged ≥80 years. Each patient was

allocated at random to four physicians who made decisions based on actual bed availability and existence of an additional bed before and after obtaining information on patient preferences. The simulations involved non-invasive ventilation (NIV), invasive mechanical ventilation (IMV), and renal replacement therapy after a period of IMV (RRT after IMV).

Results The physician participation rate was 100/217 (46 %); males without religious beliefs predominated, and

median ICU experience was 9 years. Among participants, 85.7, 78, and 62 % felt that NIV, IMV, or RRT (after IMV) was warranted, respectively. By logistic regression analysis, factors associated with admission were age <85 years, self-sufficiency, and bed availability for NIV and IMV. Factors associated with IMV were previous ICU stay (OR 0.29, 95 % CI 0.13–0.65, p = 0.01) and cancer (OR 0.23, 95 % CI 0.10–0.52, p = 0.003), and factors associated with RRT (after IMV) were living spouse (OR 2.03, 95 % CI 1.04–3.97, p = 0.038) and respiratory disease (OR 0.42, 95 % CI 0.23–0.76, p = 0.004). Agreement among physicians was low for all LSTs. Knowledge of patient preferences changed physician decisions for 39.9, 56, and 57 % of patients who disagreed with the initial physician decisions for NIV, IMV, and RRT (after IMV) respectively. An additional bed increased admissions for NIV and IMV by 38.6 and 13.6 %, respectively.

Conclusions Physician decisions for elderly patients had low agreement and varied greatly with bed availability and

knowledge of patient preferences.

Neurodevelopmental, educational and behavioral outcome at 8 years after neonatal ECMO: a nationwide

multicenter study Purpose Reporting neurodevelopmental outcome of 8-year-old children treated with neonatal extracorporeal

membrane oxygenation (ECMO). Methods In a follow-up study in 135 8-year-old children who received neonatal ECMO between 1996 and 2001 we

assessed intelligence (Revised Amsterdam Intelligence Test), concentration (Bourdon-Vos test), eye-hand coordination (Developmental Test of Visual-Motor Integration) and behavior (Child Behavior Checklist and Teacher Report Form).

Results Intelligence fell within normal range (mean IQ 99.9, SD 17.7, n = 125) with 91 % of the children

following regular education. Significantly more children attended special education (9 %) or received extra support in regular education (39 %) compared with normative data. Slower working speed (χ2 = 132.36, p < 0.001) and less accuracy (χ2 = 12.90, p < 0.001) were found on the Bourdon-Vos test (n = 123) compared with normative data. Eye-hand coordination fell within the normal range (mean 97.6, SD 14.3, n = 126); children with congenital diaphragmatic hernia scored lowest but still normally (mean 91.0, SD 16.4, n = 28). Mothers (n = 117) indicated more somatic and attention behavior problems; teachers (n = 115) indicated more somatic, social, thought, aggression and total problems compared with normative data. Mothers indicated more somatic problems than teachers (p = 0.003); teachers reported more attention problems than mothers (p = 0.036; n = 111).

Conclusions Eight-year-old children treated with neonatal ECMO fall in the normal range of intelligence with problems

with concentration and behavior. Long-term follow-up for children treated with neonatal ECMO should focus on early detection of (subtle) learning deficits.

Neurologic complications in neonates supported with extracorporeal membrane oxygenation. An analysis of

ELSO registry data Background Neurologic complications in neonates supported with extracorporeal membrane oxygenation (ECMO) are

common and diminish their quality of life and survival. An understanding of factors associated with neurologic complications in neonatal ECMO is lacking. The goals of this study were to describe the epidemiology and factors associated with neurologic complications in neonatal ECMO.

Patients and methods Retrospective cohort study of neonates (age ≤30 days) supported with ECMO using data reported to the

Extracorporeal Life Support Organization during 2005–2010. Results Of 7,190 neonates supported with ECMO, 1,412 (20 %) had neurologic complications. Birth weight <3 kg

[odds ratio (OR): 1.3; 95 % confidence intervals (CI): 1.1–1.5], gestational age (<34 weeks; OR 1.5, 95 % CI 1.1–2.0 and 34–36 weeks: OR 1.4, 95 % CI 1.1–1.7), need for cardiopulmonary resuscitation prior to ECMO (OR 1.7, 95 % CI 1.5–2.0), pre-ECMO blood pH ≤ 7.11 (OR 1.7, 95 % CI 1.4–2.1), pre-ECMO bicarbonate use (OR 1.3, 95 % CI 1.2–1.5), prior ECMO exposure (OR 2.4, 95 % CI 1.6–2.6), and use of veno-arterial ECMO (OR 1.7, 95 % CI 1.4–2.0) increased neurologic complications. Mortality was higher in patients with neurologic complications compared to those without (62 % vs. 36 %; p < 0.001).

Conclusions Neurologic complications are common in neonatal ECMO and are associated with increased mortality.

Patient factors, pre-ECMO severity of illness, and use of veno-arterial ECMO are associated with increased neurologic complications. Patient selection, early ECMO deployment, and refining ECMO management strategies for vulnerable populations could be targeted as areas for improvement in neonatal ECMO.

Pseudomonas aeruginosa Ventilator-associated Pneumonia. Predictive Factors of Treatment Failure

Rationale: The predictive factors of treatment failure for ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa (PA) remain uncertain.

Objectives: To describe PA-VAP recurrence prognosis and to identify associated risk factors in a large cohort of intensive care unit patients with PA-VAP.

Methods: From the multicenter OUTCOMEREA database (1997–2011), PA-VAP onset and recurrence were recorded. All suspected cases of VAP were confirmed by a positive quantitative culture of a respiratory sample. Multidrug-resistant PA strains were defined by the resistance to two antibiotics among piperacillin, ceftazidime, imipenem, colistine, and fluoroquinolones (FQ). An extensively resistant PA was defined by resistance to piperacillin, ceftazidime, imipenem, and FQ. A treatment failure was defined as a PA-VAP recurrence or by the death occurrence.

Measurements and Main Results: A total of 314 patients presented 393 PA-VAP. Failure occurred for 112 of them, including 79 recurrences. Susceptible, multidrug resistant, and extensively resistant PA represented 53.7%, 32%, and 14.3% of the samples, respectively. Factors associated with treatment failure were age (P = 0.02); presence of at least one chronic illness (P = 0.02); limitation of life support (P = 0.0004); a high Sepsis-Related Organ Failure Assessment score (P < 0.0001); PA bacteremia (P = 0.003); and previous use of FQ before the first PA-VAP (P = 0.0007). The failure risk was not influenced by the strain resistance profile or by the biantibiotic treatment, but decreased in case of VAP treatment that includes FQ (subdistribution hazard ratio, 0.5 [0.3–0.7]; P = 0.0006). However, the strain resistance profile slowed down the intensive care unit discharge hazard (subdistribution hazard ratio, 0.6 [0.4–1.0]; P = 0.048).

Conclusions: Neither resistance profile nor biantibiotic therapy decreased the risk of PA-VAP treatment failure. However, the profile of PA resistance prolonged the length of stay. Better evaluation of the potential benefit of an initial treatment containing FQ requires further randomized trials.

Diaphragm Dysfunction on Admission to the Intensive Care Unit. Prevalence, Risk Factors, and Prognostic

Impact—A Prospective Study Rationale: Diaphragmatic insults occurring during intensive care unit (ICU) stays have become the focus

of intense research. However, diaphragmatic abnormalities at the initial phase of critical illness remain poorly documented in humans.

Objectives: To determine the incidence, risk factors, and prognostic impact of diaphragmatic impairment on ICU admission.

Methods: Prospective, 6-month, observational cohort study in two ICUs. Mechanically ventilated patients were studied within 24 hours after intubation (Day 1) and 48 hours later (Day 3). Seventeen anesthetized intubated control anesthesia patients were also studied. The diaphragm was assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim).

Measurements and Main Results: Eighty-five consecutive patients aged 62 (54–75) (median [interquartile range]) were evaluated (medical admission, 79%; Simplified Acute Physiology Score II, 54 [44–68]). On Day 1, Ptr,stim was 8.2 (5.9–12.3) cm H2O and 64% of patients had Ptr,stim less than 11 cm H2O. Independent predictors of low Ptr,stim were sepsis (linear regression coefficient, −3.74; standard error, 1.16; P = 0.002) and Simplified Acute Physiology Score II (linear regression coefficient, −0.07; standard error, 1.69; P = 0.03). Compared with nonsurvivors, ICU survivors had higher Ptr,stim (9.7 [6.3–13.8] vs. 7.3 [5.5–9.7] cm H2O; P = 0.004). This was also true for hospital survivors versus nonsurvivors (9.7 [6.3–13.5] vs. 7.8 [5.5–10.1] cm H2O; P = 0.004). Day 1 and Day 3 Ptr,stim were similar.

Conclusions: A reduced capacity of the diaphragm to produce inspiratory pressure (diaphragm dysfunction) is frequent on ICU admission. It is associated with sepsis and disease severity, suggesting that it may represent another form of organ failure. It is associated with a poor prognosis.

Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation

Rationale: Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear.

Objectives: To estimate whether mortality in mechanically ventilated patients has changed over time.

Methods: Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models.

Measurements and Main Results: We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied PEEP (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80–0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67–0.92).

Conclusions: Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved.

Effects of Prone Positioning on Lung Protection in Patients with Acute Respiratory Distress Syndrome

Rationale: Positive end-expiratory pressure (PEEP) and prone positioning may induce lung recruitment and affect alveolar dynamics in acute respiratory distress syndrome (ARDS). Whether there is interdependence between the effects of PEEP and prone positioning on these variables is unknown.

Objectives: To determine the effects of high PEEP and prone positioning on lung recruitment, cyclic recruitment/derecruitment, and tidal hyperinflation and how these effects are influenced by lung recruitability.

Methods: Mechanically ventilated patients (Vt 6 ml/kg ideal body weight) underwent whole-lung computed tomography (CT) during breath-holding sessions at airway pressures of 5, 15, and 45 cm H2O and Cine-CTs on a fixed thoracic transverse slice at PEEP 5 and 15 cm H2O. CT images were repeated in supine and prone positioning. A recruitment maneuver at 45 cm H2O was performed before each PEEP change. Lung recruitability was defined as the difference in percentage of nonaerated tissue between 5 and 45 cm H2O. Cyclic recruitment/derecruitment and tidal hyperinflation were determined as tidal changes in percentage of nonaerated and hyperinflated tissue, respectively

Measurements and Main Results: Twenty-four patients with ARDS were included. Increasing PEEP from 5 to 15 cm H2O decreased nonaerated tissue (501 ± 201 to 322 ± 132 grams; P < 0.001) and increased tidal-hyperinflation (0.41 ± 0.26 to 0.57 ± 0.30%; P = 0.004) in supine. Prone positioning further decreased nonaerated tissue (322 ± 132 to 290 ± 141 grams; P = 0.028) and reduced tidal hyperinflation observed at PEEP 15 in supine patients (0.57 ± 0.30 to 0.41 ± 0.22%). Cyclic recruitment/derecruitment only decreased when high PEEP and prone positioning were applied together (4.1 ± 1.9 to 2.9 ± 0.9%; P = 0.003), particularly in patients with high lung recruitability.

Conclusions: Prone positioning enhances lung recruitment and decreases alveolar instability and hyperinflation observed at high PEEP in patients with ARDS.

Effects of dobutamine on systemic, regional and microcirculatory perfusion

parameters in septic shock: a randomized, placebo-controlled, double-blind,

crossover study

Introduction

dobutamine, increase cardiac output , central (ScvO2) or mixed venous oxygen saturations (SvO2), and eventually hepatosplanchnic perfusion.

a marked improvement in microcirculatory derangements was observed after 2 h of dobutamine infusion.

current guidelines recommend dobutamine for septic shock in patients with low cardiac output or with persistent hypoperfusion after initial resuscitation.

However, other studies have yielded conflicting data concerning the effects of dobutamine on hepatosplanchnic and microcirculatory perfusion, and it remains unclear whether it can improve lactate clearance or peripheral perfusion.

Dobutamine has been associated with serious adverse events.

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Design This was a prospective, randomized, double-blind, placebo-controlled,

crossover study, conducted from February 2011 to August 2012 in a mixed 16-bed ICU.

patients should have a pulmonary artery catheter in place, HGB＞8 g/dl and temperature＜39 C and should have maintained a pulse pressure variation ＜10 % for at least 1 h without fluid challenges.

A continuous infusion of normal saline Norepinephrine infusion was adjusted to keep the mean arterial pressure

≥65 mmHg. No new vasopressors or inotropes were administered after starting the

study in case of cardiovascular instability, such as life-threatening

hypotension, tachycardia ＞150 bpm, acute atrial fibrillation or ST changes in the cardiac monitor, the study had to be stopped and randomization disclosed.

Inclusion

within 24 h of septic shock onset diagnosed according to the 2001 Consensus Definition a basal arterial lactate＞2.4 mmol/l Mechanical ventilation

Exclusion Pregnancy refractory hypotension, acute coronary syndrome within the last 3 months non-sinus rhythm, heart rate＞140 bpm, previous use of dobutamine during the last 72 h, cardiac index＜2.5 l/min/m2, anticipated surgery dialysis during the study period, Child B or C liver cirrhosis, a do-not-resuscitate status.

Result

Result

Result

Result Concerning the effects of dobutamine on macrohemodynamic parameters, we

found an increase of 15 % in the CI, 12 % in the heart rate and 16 % in the left ventricle ejection fraction

Dobutamine in doses of 5 mcg/kg/min had no significant beneficial effects in any microcirculatory variables.

In conclusion, dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic peripheral perfusion parameters

Vasopressin Compared with Norepinephrine Augments the Decline

of Plasma Cytokine Levels in Septic Shock

Introduction Cytokines increase early in septic shock, and may predict mortality. Persistence of IL-6 and TNF-a predicted poor outcomes in the first 48 hours of

septic shock. differences in levels of IL-1, 4, 6, 8, MCP-1and granulocyte colony–

stimulating factor between survivors and nonsurvivors. MCP-1 was prognostic for 28-day mortality.

Vasopressin decreases proinflammatory cytokines in animal models。

Method We evaluated 39 cytokines, chemokines, and growth factors. VASST is a multicenter, blinded RCT. We randomly selected patients with baseline (with 2h of study drug)and

24-hour plasma specimens. patients were over 16 years of age and had septic shock (two or more SIRS

criteria, infection, new organ, and hypotension despite fluid resuscitation requiring vasopressor support [＞5 ug/min of norepinephrine for 6 h]).

Exclusion criteria were unstable coronary syndromes, acute mesenteric

ischemia, severe chronic heart disease, and vasospastic diathesis.

Study Drug Infusion Patients were randomized to blinded infusions of vasopressin (0.01–0.03

U/min) or norepinephrine (5–15 mg/min) that were titrated and weaned by protocol to maintain a mean arterial pressure of 65–75 mm Hg.

Study drug infusion continued until the patient died, had a serious adverse event, or improved (open-label vasopressors not required).

Severity of shock was defined less severe shock—norepinephrine 5–15 mg/min; more severe septic shock—norepinephrine greater than 15 mg/min.

Result

Result

Result In VASST, vasopressin was not associated with a reduction in 28-day

mortality (35.4%) compared with norepinephrine (39.3%; P 1/4 0.26). Survivors (compared with nonsurvivors) had significantly greater

decreases of overall cytokine levels from baseline to 24 hours. The differences in changes in plasma cytokines over 24 hours between

survivors and nonsurvivors were generally less pronounced in less severe than in more severe septic shock.

Only the overall cytokine level, IP-10, and cluster 3 cytokines (IL-6, IL-8, and G-CSF) declined significantly more in survivors than in nonsurvivors who had less severe shock.

IP-10 (P 1/4 0.03) and G-CSF (P 1/4 0.04) decreased significantly more in the vasopressin than in the norepinephrine group with less severe shock.

in more severe shock, vasopressin did decrease one cytokine (GM-CSF) more than did norepinephrine.

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