Critical Care and Anaesthesia- June 2011

Critical Care & Anaesthesia – Evidence Update

June 2011

Welcome to the first bulletin highlighting new evidence published on selected topics

relating to Critical Care, Anaesthesia, Pain and Resuscitation. Journals such as –

Lancet, NEJM, JAMA, BMJ and American Journal of Critical Care Medicine have been

scanned to identify relevant articles. Articles from other journals as retrieved via

searches on MEDLINE and EMBASE are also listed. Monthly updates from July 2011

will feature evidence published in the previous four weeks. Full text articles can be

accessed via your HEFT Athens ID.

Ventilator associated pneumonia

Title: Intermittent subglottic secretion drainage and ventilator-associated pneumonia [2]

Citation:  American  Journal  of Respiratory  and  Critical  Care  Medicine,   May  2011,  vol./is.

183/10(1435-1436), 1073-449X;1535-4970 (15 May 2011) Author(s): Taylor N.J., Auzinger

G. Full Text: Available in fulltext at ProQuest (Legacy Platform)

Title: Intermittent subglottic secretion drainage and ventilator-associated pneumonia [1]

Citation:  American  Journal  of Respiratory  and  Critical  Care  Medicine,   May  2011,  vol./is.

183/10(1435),  1073-449X;1535-4970  (15  May  2011)  Author(s): Silvestri  L.,  Piacente  N.,

Van  Saene  H.K.F.,   Gregori  D.,  Zandstra  D.F.  Full  Text: Available  in  fulltext at  ProQuest

(Legacy Platform)

Title: Review: Diagnostics and epidemiology in ventilator-associated pneumonia

Citation:  Therapeutic  Advances in  Respiratory  Disease,  April  2011,  vol./is.  5/2(121-130),

1753-4658;1753-4666   (April  2011)  Author(s): Shorr  A.F.,  Chan   C.M.,   Zilberberg  M.D.

Abstract:  Ventilator-associated   pneumonia    (VAP)   represents   a   common    nosocomial

complication   arising  in  the  intensive  care  unit.  Owing  to  concerns regarding  the  excess

morbidity related to VAP, multiple interventions for preventing this syndrome exist. Despite

controversy regarding  the  optimal  diagnostic  approach  to  VAP,  clinicians  now face many

external  pressures  to  try  to  reduce,  if  not  eliminate,   VAP.  In   fact,  some  organizations

consider VAP an entirely preventable event. However, any dialog regarding the outcomes

and burden of VAP must rest on an understanding and appreciation of both the diagnostic

complexities surrounding VAP and the epidemiology of this condition. In addition, the issues

of diagnostics  and  epidemiology   are  closely  linked.  The  means  employed  for diagnosing

VAP  certainly  affect the  observed  prevalence  of  VAP.  Despite  these  concerns,  several

general themes emerge in the literature describing VAP epidemiology. First, VAP rates vary

based on the diagnostic approach employed. Second, select cohorts of patients are at high

risk for VAP, and patient case-mix clearly influences the epidemiology of VAP. Third, rates of

VAP  appear  higher  outside  the  US,  irrespective of the  diagnostic  paradigm  utilized.  The

Author(s), 2011.

Title: Review: Strategies in the prevention of ventilator-associated pneumonia

Citation:  Therapeutic  Advances in  Respiratory  Disease,  April  2011,  vol./is.  5/2(131-141),

1753-4658;1753-4666   (April   2011)   Author(s):  Maselli    D.J.,   Restrepo   M.I.    Abstract:

Ventilator-associated pneumonia (VAP) remains a significant problem in the hospital setting,

with very high morbidity, mortality, and cost. We performed an evidence-based review of the

literature    focusing   on    clinically    relevant    pharmacological    and    nonpharmacological

interventions to prevent VAP. Owing to the importance of this condition the implementation

of preventive measures is paramount in the care of mechanically ventilated patients. There

is evidence that these measures decrease the incidence of VAP and improve outcomes in

the  intensive  care  unit.  A  multidisciplinary   approach,  continued  education,  and  ventilator

protocols  ensure the  implementation   of these  measures.  Future  research will continue  to

investigate cost/benefit relationships, antibiotic resistance, as well as newer technologies to

prevent  contamination   and  aspiration  in  mechanically  ventilated  patients.  The  Author(s),

2010.

Title: Relationship between inhaled beta2-agonists and ventilator-associated pneumonia: A

cohort study

Citation:  Critical  Care  Medicine,   April  2011,  vol./is.  39/4(725-730),  0090-3493;1530-0293

(April 2011) Author(s): Jaillette E., Nseir S. Abstract: Objective: To determine the impact of

aerosolized bronchodilators on ventilator-associated pneumonia. Design: Prospective cohort

study. Setting:  A 30-bed  medical  and  surgical  intensive  care  unit.  Methods:  All  intubated

patients requiring mechanical ventilation for >48 hrs were eligible during a 13-month period.

Nebulized beta2-agonists were administered at the intensive care unit physicians discretion.

Ventilator-associated pneumonia definition included clinical and quantitative microbiological

criteria. Only first ventilator-associated pneumonia episodes were analyzed. Risk factors for

ventilator-associated   pneumonia    were   determined    using   univariate    and   multivariate

analyses.  The   influence  of  inhaled   beta2-agonists  on   ventilator-associated  pneumonia

occurrence  was also  adjusted  for  confounding  factors using  Coxs  proportional-hazards

model. RESULTS:: Ventilator-associated pneumonia was diagnosed in 137 (31%) of the 439

enrolled  patients.  Ventilator-associated  pneumonia   was early-onset  in  14  (10%)  patients.

The  incidence  rate  of ventilator-associated  pneumonia   was 20  per  1,000  ventilator  days.

Ventilator-associated  pneumonia   was polymicrobial   in  16  (11%)  patients,  and  related  to

multidrug-resistant   bacteria   in   42  (28%)  patients.   Most   cases  of  ventilator-associated

pneumonia    were   caused   by   Gram-negative    bacteria.   Inhaled    beta2-agonists    were

significantly   more    frequently   used   in   patients   with   ventilator-associated   pneumonia

compared  with those  without ventilator-  associated  pneumonia  (49%  vs. 34%,  odds  ratio

[95%   confidence   interval]   =   1.9   [1.2-2.8],   p   =   .003).   Multivariate   analysis   identified

aerosolized beta2-agonists (odds ratio [95% confidence interval] = 1.7 [1.1-2.6], p = .012),

Simplified   Acute  Physiology  Score  II   at  intensive  care  unit  admission  (odds  ratio  [95%

confidence interval] = 1.01 [1.001-1.02] per point, p = .031), and red blood cell transfusion

(odds ratio [95% confidence interval] = 2 [1.3-3.1], p = .001) as independent risk factors for

ventilator-associated  pneumonia.   Coxs  proportional-hazards  model  also  identified  inhaled

beta2-agonists   as  a  risk   factor  for  ventilator-associated   pneumonia   (odds  ratio   [95%

confidence   interval]   =   1.52   [1.06-2.19],   p   =   .021).   Conclusion:   Use   of   aerosolized

bronchodilators in intensive care unit mechanically ventilated patients is an independent risk

factor for ventilator-associated pneumonia.   Full  Text: Available  in  fulltext at  MD  Consult;

Note: You will need to register (free of charge) with MD Consult the first time you use it.

Title: Inhaled therapy and ventilator-associated pneumonia: A breath of suspicion in the air?

Citation:  Critical  Care  Medicine,   April  2011,  vol./is.  39/4(893-894),  0090-3493;1530-0293

(April 2011) Author(s): Clavel M. Full Text: Available in fulltext at MD Consult; Note: You

will need to register (free of charge) with MD Consult the first time you use it.

Title: Prognostic value of dynamic soluble triggering receptor expressed on myeloid cells in

bronchoalveolar lavage fluid of patients with ventilator-associated pneumonia

Citation: Respirology, April 2011, vol./is. 16/3(487-494), 1323-7799;1440-1843 (April 2011)

Author(s): Wu C.-L.,  Lu Y.-T.,  Kung  Y.-C.,  Lee C.-H.,   Peng  M.-J.  Abstract: Background

and objective: The aim of this study was to investigate the time course, and correlation with

prognosis, of BAL fluid concentrations of soluble triggering receptor expressed on myeloid

cells (sTREM-1) in patients with ventilator-associated pneumonia (VAP). Methods: The study

included 35 patients with clinically diagnosed VAP, eight of whom were BAL fluid culture-

negative and 27 BAL fluid culture-positive (16 survivors, 11 non-survivors). sTREM-1 levels

were measured   in  BAL  fluid  of  these  mechanically   ventilated   patients,  at  the  time   of

diagnosis, on days 4-5 and on days 7-9. The time course of this biomarker and its prognostic

value for outcome in patients with culture-positive VAP were assessed. Results: sTREM-1

concentrations  were significantly  greater  in  culture-positive  VAP  patients  than  in  culture-

negative   VAP  patients.  sTREM-1    levels  decreased  significantly  with  time   in   surviving

patients with culture-positive VAP, but increased significantly with time in non-survivors. In

contrast,      PaO₂/fraction            of   inspired      oxygen     (FiO₂) increased

significantly with time in survivors and decreased significantly with time in non-survivors. At a

cut-off value of -10 pg/mL 7-9 days after initial diagnosis, sTREM levels had a sensitivity of

90%   and    a   specificity   of   87.5%    for   predicting    mortality.    Conclusions:    sTREM-1

concentrations in BAL fluid are of potential prognostic value in patients with VAP. 2011 The

Authors Respirology 2011 Asian Pacific Society of Respirology.

Title:  Bronchoalveolar  lavage   in   the   diagnosis   of  ventilator-associated  pneumonia:   to

quantitate or not, that is the question.

Citation:  American  Surgeon,   March  2011,  vol./is.  77/3(297-303),  0003-1348;0003-1348

(2011  Mar)  Author(s): Riaz  OJ,  Malhotra  AK, Aboutanos  MB,  Duane  TM,  Goldberg  AE,

Borchers CT, Martin NR, Ivatury RR Abstract: Quantitative bronchoalveolar lavage (BAL) is

used  to  diagnose   ventilator-associated  pneumonia   (VAP).  We   prospectively  compared

semiquantitative  (SQ)  and  quantitative  (Qu)  culture  of BAL  for VAP  diagnosis.  Ventilated

patients suspected of VAP underwent bronchoscopic BAL. BAL fluid was examined by both

Qu  (colony-forming units  [CFUs]/mL)   and  SQ  culture  (none,  sparse, moderate,  or heavy)

and  results  were compared.  VAP  was defined  as 105  CFU/mL or    greater  on Qu  culture.

Over  36 months,   319 BALs  were performed.  Sixty-three of  319 (20%) showed diagnostic

growth by  Qu  culture  identifying  a  total  of 81  organisms  causing  VAP.  All  63  specimens

showed growth of  some  organism(s)  on  SQ  culture  with 79  of  81  causative  organisms

identified and two (Pseudomonas, one; Corynebacterium, one) not identified. The remaining

256 specimens did not meet the threshold for VAP by the Qu method. Among these, 79 did

not show any growth on SQ culture. Among the 240 specimens showing some growth on SQ

culture, a total of 384 organisms were identified. VAP rates in relation to strength of growth

on SQ culture were: sparse, 10 of 140 (7%); moderate, 24 of 147 (16%); and heavy, 45 of 97

(46%). Sensitivity (Sn), specificity (Sp), positive (PPV), and negative (NPV) predictive values

of  SQ  culture  of  BAL  fluid  for the  diagnosis  of VAP  were 97,  21,  21,  and  97  per  cent,

respectively. Nonquantitative culture of BAL fluid is fairly accurate in ruling out VAP (high Sn

and NPV). It however has poor Sp and PPV and using this method will lead to unnecessary

antimicrobial use with its attendant complications of toxicity, cost, and resistance. Full Text:

Available in fulltext at EBSCO Host Available in fulltext at ProQuest (Legacy Platform)

Title: A European care bundle for management of ventilator-associated pneumonia.

Citation: Journal of Critical Care, February 2011, vol./is. 26/1(3-10), 0883-9441;1557-8615

(2011   Feb)   Author(s):  Rello    J,   Chastre   J,   Cornaglia    G,   Masterton   R   Abstract:

BACKGROUND:    Although  there  is  a  wealth of  guidance  concerning  the  management   of

patients  with ventilator-associated  pneumonia   (VAP),  compliance  with  recommendations

concerning   optimal    treatment   practices  is   highly   variable.METHODS:     This   document

presents a comprehensive care bundle package addressing all aspects of       VAP diagnosis

and   treatment   in   an  attempt   to  promote   guideline-compliant    practices.  Uniquely,   the

development of these care bundles used a formalized method to assess the supporting data,

based on multicriteria decision analysis.RESULTS: This system allowed the numerous VAP

management parameters identified from recent European guidelines to be ranked according

to  defined  criteria.  The  resulting  VAP  care bundles  are  (a)  diagnosis:  early  chest x-rays

within 1 hour, immediate reporting of respiratory secretions Gram staining, and (b) therapy:

immediate    treatment,   empiric   therapy  based  on  local  pathogens   and  risk  factors,  de-

escalation,   assessment   of  response   within  72   hours,   and   short   therapy   duration   if

feasible.CONCLUSION:      Adoption    of    these    care    bundles    should    rationalize    VAP

management practices and facilitate the development of consistent and guideline-compliant

care processes. Copyright Copyright 2011 Elsevier Inc. All rights reserved.

Title: Modifying endotracheal tubes to prevent ventilator-associated pneumonia.

Citation:  Current  Opinion  in  Infectious  Diseases,  April  2011,  vol./is.  24/2(157-62),  0951-

7375;1535-3877  (2011  Apr)  Author(s): Coppadoro   A,  Berra  L,  Bigatello   LM   Abstract:

PURPOSE OF REVIEW: The endotracheal tube (ETT) is the main avenue leading to airway

contamination   and  subsequent  ventilator-associated  pneumonia  (VAP)  during  mechanical

ventilation.  A  number  of  modifications  to  the  ETT   are  available,  aimed   at  reducing  the

incidence   of  VAP.  We   review here  available   systems  and   devices,  and   clinical   data

regarding their efficacy.RECENT FINDINGS: Three main modifications of ETTs have been

developed:  coating  with antimicrobials,   adding  a  suction  channel  for the  removal  of  oro-

pharyngeal secretions, and modifying the design of the cuff. Each of these interventions has

been shown to limit bacterial colonization of the distal airways and to decrease the incidence

of VAP. Data on their ultimate effect on related clinical outcomes are still lacking.SUMMARY:

Modifications   of  ETTs   aimed   at  decreasing  the  onset  of  VAP  show promising   results.

However, the  lack  of  a  significant  effect on  outcomes  prompts  us  to  use  caution  before

recommending their widespread use.

Acute lung injury(ALI)/Adult respiratory distress syndrome (ARDS)

Title: Update in acute lung injury and critical care 2010

Citation:  American  Journal  of Respiratory  and  Critical  Care  Medicine,   May  2011,  vol./is.

183/9(1147-1152), 1073-449X;1535-4970 (01 May 2011) Author(s): Vadasz I., Sznajder J.I.

Full Text: Available in fulltext at ProQuest (Legacy Platform)

Title: ANGPT2 genetic variant is associated with trauma-associated acute lung injury and

altered plasma angiopoietin-2 isoform ratio

Citation:  American  Journal  of Respiratory  and  Critical  Care  Medicine,   May  2011,  vol./is.

183/10(1344-1353),  1073-449X;1535-4970  (15  May  2011)  Author(s): Meyer  N.J.,  Li  M.,

Feng  R.,   Bradfield  J.,  Gallop   R.,   Bellamy   S.,  Fuchs  B.D.,   Lanken  P.N.,   Albelda  S.M.,

Rushefski M., Aplenc R., Abramova H., Atochina-Vasserman E.N., Beers M.F., Calfee C.S.,

Cohen M.J., Pittet J.-F., Christiani D.C., O'Keefe G.E., Ware L.B., May A.K., Wurfel M.M.,

Hakonarson H., Christie J.D. Abstract: Rationale: Acute lung injury (ALI) acts as a complex

genetic   trait,   yet  its  genetic   risk  factors  remain   incompletely   understood.   Large-scale

genotyping has not previously been reported for ALI. Objectives: To identify ALI risk variants

after major trauma using a large-scale candidate gene approach. Methods: We performed a

two-stage genetic association study. We derived findings in an African American cohort (n =

222)  using  a  cardiopulmonary  disease-centric 50K  single  nucleotide  polymorphism  (SNP)

array. Genotype and haplotype distributions were compared between subjects with ALI and

without  ALI,   with  adjustment   for  clinical   factors. Top   performing  SNPs   (P   <  10<sup>-

4</sup>)  were tested  in  a  multicenter  European   American  trauma-associated  ALI  case-

control population (n = 600 ALI; n = 2,266 population-based control subjects) for replication.

The  ALI-associated  genomic   region  was sequenced,  analyzed  for  in  silico  prediction  of

function,  and  plasma  was assayed by  ELISA   and  immunoblot.   Measurements  and  Main

Results:  Five  SNPs  demonstrated  a  significant  association  with ALI  after adjustment  for

covariates in Stage I. Two SNPs     in ANGPT2 (rs1868554 and rs2442598)     replicated their

significant  association  with ALI  in  Stage II.   rs1868554  was robust  to multiple   comparison

correction: odds ratio 1.22 (1.06-1.40), P = 0.0047. Resequencing identified predicted novel

splice  sites  in  linkage   disequilibrium   with  rs1868554,  and  immunoblots   showed  higher

proportion of  variant angiopoietin-2 (ANG2) isoform associated with rs1868554T     (0.81 vs.

0.48; P = 0.038). Conclusions: An ANGPT2 region is associated with both ALI and variation

in  plasma  angiopoietin-2  isoforms.  Characterization  of the  variant  isoform  and  its  genetic

regulation may yield important insights about ALI pathogenesis and susceptibility. Full Text:

Available in fulltext at ProQuest (Legacy Platform)

Title:  Focusing   on  the   flood:  Targeting   functional   polymorphisms   in   ALI   permeability

pathways

Citation:  American  Journal  of Respiratory  and  Critical  Care  Medicine,   May  2011,  vol./is.

183/10(1287-1289),  1073-449X;1535-4970  (15  May  2011)  Author(s): Garcia  J.G.N.   Full

Text: Available in fulltext at ProQuest (Legacy Platform)

Title: Lung regional metabolic activity and gas volume changes induced by tidal ventilation

in patients with acute lung injury

Citation:  American  Journal  of Respiratory  and  Critical  Care  Medicine,   May  2011,  vol./is.

183/9(1193-1199), 1073-449X;1535-4970 (01 May 2011) Author(s): Bellani G., Guerra L.,

Musch G., Zanella A., Patroniti N., Mauri T., Messa C., Pesenti A.

Abstract: Rationale:   During  acute lung  injury (ALI),  mechanical ventilation can aggravate

inflammation by promoting alveolar distension and cyclic recruitment-derecruitment. As an

estimate  of the  intensity  of inflammation,metabolic   activity  can  bemeasured  by positrone-

mission  tomography  imaging   of [18F]fluoro-2-deoxy-D-glucose.  Objectives:  To  assess the

relationship   between  gas  volume   changes  induced   by  tidal   ventilation   and  pulmonary

metabolic activity in patients with ALI. Methods: In 13 mechanically ventilated patients with

ALI and relatively high positive end-expiratory pressure, we performed a positron emission

tomography  scan  of  the  chest  and  three  computed  tomography  scans: at  mean   airway

pressure,                          end-expiration,                           and                           end-inspiration.

Metabolicactivitywasmeasuredfromthe[18F]fluoro-2-deoxy-D-glucose     uptake     rate.     The

computed tomography scans were used to classify lung regions as derecruited throughout

the    respiratory   cycle,   undergoing    recruitment-derecruitment,    and   normally    aerated.

Measurements and Main Results: Metabolic activity of normally aerated lung was positively

correlated both with plateau pressure, showing a pronounced increase above 26 to 27 cm

H2O, and with regional VT normalized by end-expiratory lung gas volume. This relationship

did  not  appear  to  be  caused  by  a  higher  underlying  parenchymal  metabolic   activity  in

patients with higher plateau pressure. Regions undergoing cyclic recruitment-derecruitment

did not have higher metabolic activity than those collapsed throughout the respiratory cycle.

Conclusions:  In  patients  with  ALI  managed   with relatively  high  end-expiratory  pressure,

metabolic activity of aerated regions was associated with both plateau pressure and regional

VT  normalized   by  end-expiratory  lung  gas  volume,   whereas no  association  was found

between cyclic recruitment- derecruitment and increased metabolic activity. Copyright 2011

American Thoracic Society. Full Text: Available in fulltext at ProQuest (Legacy Platform)

Title:  Early  corticosteroids in  severe influenza  A/H1N1  pneumonia  and  acute  respiratory

distress syndrome

Citation:  American  Journal  of Respiratory  and  Critical  Care  Medicine,   May  2011,  vol./is.

183/9(1200-1206),   1073-449X;1535-4970   (01   May   2011)   Author(s):  Brun-Buisson  C.,

Richard J.-C.M., Mercat A., Thiebaut A.C.M., Brochard L. Abstract: Rationale: Despite their

controversial role,  corticosteroids are  often administered  to  patients  with adult  respiratory

distress syndrome (ARDS) secondary to viral pneumonia. Objectives: To analyze the impact

of corticosteroid therapy on outcomes   of  patients  having  ARDS  associated with influenza

A/H1N1 pneumonia. Methods: Patients from the French registry of critically ill patients with

influenza  A/H1N1v  2009  infection  were selected  if  fulfilling  criteria  for ARDS,   excluding

patients having other indication for corticosteroids, or decompensated underlying disease as

the  primary  cause  for intensive  care  unit  admission.  Survival  to  hospital  discharge  was

analyzed using  Cox regression,  accounting for  the time to administration of     steroids, and

after adjustment  on the propensity for receiving steroid therapy.     Measurements and Main

Results: Of 208 patients with ARDS, 83 (39.9%) received corticosteroids (median initial dose

of 270 mg   equivalent  hydrocortisone per  day for  a median of   11 d).  Steroid therapy was

associated with death, both in crude analysis (33.7 vs. 16.8%; hazard ratio, 2.4; 95% CI, 1.3-

4.3;   P   5  0.004)   and   after  propensity  score-adjusted  analysis  (adjusted   hazard  ratio,

2.82;95%  CI,   1.5-5.4;  P  5  0.002),  controlling  for  an  admission   severity Simplified   Acute

Physiology  Score,  version  3,  greater  than  50,  initial  administration   of  vasopressors, and

immunodepression. Early therapy (<= 3 d of mechanical ventilation) appeared more strongly

associated  with mortality   than  late  administration.   Patients   receiving  steroids  had  more

acquired pneumonia and a trend to a longer duration of ventilation. Conclusions: Our study

provides  no  evidence   of  a   beneficial   effect  of  corticosteroids  in   patients   with  ARDS

secondary to influenza pneumonia, but suggests that very early corticosteroid therapy may

be  harmful.  Copyright  2011  American  Thoracic  Society.  Full  Text: Available  in  fulltext at

ProQuest (Legacy Platform)

Title: Con: Corticosteroids Are Not Indicated for Treatment of Acute Lung Injury from H1N1

Viral Pneumonia.

Citation:  American  Journal   of  Respiratory  &  Critical  Care  Medicine,   May  2011,  vol./is.

183/9(1127-8),  1073-449X;1535-4970  (2011  May  1)  Author(s): Matthay  MA,  Liu  KD  Full

Text: Available in fulltext at ProQuest (Legacy Platform)

Title: A metabolic window into acute respiratory distress syndrome: stretch, the "baby" lung,

and atelectrauma.

Citation:  American  Journal   of  Respiratory  &  Critical  Care  Medicine,   May  2011,  vol./is.

183/9(1120-2), 1073-449X;1535-4970 (2011 May 1) Author(s): Bersten AD, Kavanagh BP

Full Text: Available in fulltext at ProQuest (Legacy Platform)

Title: The burden of functional recovery from ARDS.

Citation:  New  England   Journal   of  Medicine,   April  2011,  vol./is.  364/14(1358-9),  0028-

4793;1533-4406 (2011 Apr 7) Author(s): Hall JB, Kress JP

Full Text: Available in print at Good Hope Hospital Library

Title: Epithelial cell death is an important contributor to oxidant-mediated acute lung injury.

Citation:  American  Journal  of  Respiratory  &  Critical   Care  Medicine,   April  2011,  vol./is.

183/8(1043-54), 1073-449X;1535-4970 (2011 Apr 15) Author(s): Budinger GR, Mutlu GM,

Urich D, Soberanes S, Buccellato LJ, Hawkins K, Chiarella SE, Radigan KA, Eisenbart J,

Agrawal H,  Berkelhamer   S,  Hekimi   S,  Zhang  J,  Perlman   H,  Schumacker  PT,   Jain  M,

Chandel NS

Abstract: RATIONALE: Acute lung injury and the acute respiratory distress syndrome are

characterized by increased lung oxidant stress and apoptotic cell death. The contribution of

epithelial   cell  apoptosis  to  the  development   of  lung  injury  is  unknown.OBJECTIVES:    To

determine whether oxidant-mediated activation of the intrinsic or extrinsic apoptotic pathway

contributes to the development of acute lung injury.METHODS: Exposure of tissue-specific

or  global  knockout  mice  or  cells  lacking  critical  components  of the  apoptotic  pathway to

hyperoxia, a well-established mouse model of oxidant-induced lung injury, for measurement

of cell death, lung injury, and survival.MEASUREMENTS AND MAIN RESULTS: We found

that the overexpression of SOD2 prevents hyperoxia-induced BAX activation and cell death

in primary alveolar epithelial cells and prolongs the survival of mice exposed to hyperoxia.

The conditional loss of BAX and BAK in the lung epithelium prevented hyperoxia-induced

cell   death   in   alveolar   epithelial   cells,   ameliorated   hyperoxia-induced   lung   injury,   and

prolonged survival in mice. By contrast, Cyclophilin D-deficient mice were not protected from

hyperoxia,  indicating   that   opening   of  the   mitochondrial   permeability   transition   pore  is

dispensable   for  hyperoxia-induced  lung   injury.  Mice   globally   deficient  in   the  BH3-only

proteins BIM, BID, PUMA, or NOXA, which are proximal upstream regulators of BAX and

BAK,  were not  protected  against  hyperoxia-induced  lung  injury  suggesting  redundancy of

these  proteins  in  the  activation  of  BAX  or  BAK.CONCLUSIONS:     Mitochondrial   oxidant

generation initiates BAX- or BAK-dependent alveolar epithelial cell death, which contributes

to  hyperoxia-induced  lung   injury.  Full   Text:  Available  in   fulltext  at   ProQuest   (Legacy

Platform)

Title: Recombinant surfactant protein C-based surfactant for patients with severe direct lung

injury. Citation: American Journal of Respiratory & Critical Care Medicine, April 2011, vol./is.

183/8(1055-61),  1073-449X;1535-4970   (2011  Apr  15)  Author(s): Spragg  RG,   Taut  FJ,

Lewis JF,   Schenk  P,   Ruppert   C,  Dean   N,  Krell  K,  Karabinis  A,  Gunther   A  Abstract:

RATIONALE: Patients with acute lung injury have impaired function of the lung surfactant

system.   Prior   clinical   trials   have   shown  that   treatment   with  exogenous   recombinant

surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation

and have suggested that treatment of patients with severe direct lung injury may decrease

mortality.OBJECTIVES:     Determine   the  clinical   benefit  of  administering   an  rSP-C-based

synthetic  surfactant  to   patients   with  severe  direct   lung   injury   due   to   pneumonia    or

aspiration.METHODS:     A  prospective  randomized   blinded   study  was  performed  at  161

centers in 22 countries. Patients were randomly allocated to receive usual care plus up to

eight doses of rSP-C surfactant administered over 96 hours (n = 419) or only usual care (n =

424).MEASUREMENTS     AND  MAIN   RESULTS:    Mortality  to  28  days  after  treatment,  the

requirement for mechanical ventilation, and the number of nonpulmonary organ failure-free

days were not  different between study groups.  In  contrast to  prior  studies,  there  was no

improvement in oxygenation in patients receiving surfactant compared with the usual care

group.  Investigation  of  the  possible  reasons  underlying  the  lack  of efficacy suggested  a

partial inactivation of rSP-C surfactant caused by a step of the resuspension process that

was introduced with this study.CONCLUSIONS: In this study, rSP-C-based surfactant was of

no  clinical   benefit  to   patients  with  severe  direct  lung   injury.   The   unexpected  lack   of

improvement   in  oxygenation,  coupled  with the  results  of  in  vitro  tests,  suggest  that  the

administered   suspension  may   have  had   insufficient  surface  activity  to   achieve  clinical

benefit. Full Text: Available in fulltext at ProQuest (Legacy Platform)

Title: Opening the lungs: Do it slowly, please

Citation: Critical Care Medicine, May 2011, vol./is. 39/5(1221-1222), 0090-3493;1530-0293

(May  2011)  Author(s): Plotz  F.B.,  Groeneveld  A.J.  Full  Text: Available  in  fulltext at  MD

Consult; Note: You will need to register (free of charge) with MD Consult the first time you

use it.

Title: Mortality prediction in adult respiratory distress syndrome: Get real

Citation: Critical Care Medicine, May 2011, vol./is. 39/5(1210-1211), 0090-3493;1530-0293

(May 2011) Author(s): Kipnis E. Full Text: Available in fulltext at MD Consult; Note: You will

need to register (free of charge) with MD Consult the first time you use it.

Sepsis – the use of statins, biomarker MMP9

Title: Statins in prevention and treatment of severe sepsis and septic shock

Citation:  European  Journal  of Internal  Medicine,  April  2011,  vol./is.  22/2(125-133),  0953-

6205 (April 2011) Author(s): Kouroumichakis I., Papanas N., Proikaki S., Zarogoulidis P.,

Maltezos E.

Abstract: Severe  sepsis is  an  infection-induced  inflammatory   syndrome  that  can  lead  to

multi-organ   dysfunction  and  continues  to  be  a  major   cause  of  morbidity   and  mortality

worldwide. Because numerous cascades are triggered during sepsis, selective blocking of

inflammatory  mediators  may  be  insufficient to  arrest this  process, and  recent  therapeutic

approaches have proven controversial. Statins are the most commonly prescribed agents for

hypercholesterolaemia  and  dominate  the  area of  cardiovascular risk  reduction.  Moreover,

these drugs have a variety of actions that are independent of their lipid lowering effect. Such

anti-inflammatory,   antioxidant,   immunomodulatory,   and  antiapoptotic  features  have  been

collectively referred to as pleiotropic effects. By virtue of their pleiotropic effects, statins have

also emerged as potentially useful in various critical care areas such as bacteraemia, the

early phases of sepsis and septic shock, as well as the management of serious infections.

This review outlines current evidence on the use of statins for preventing and treating sepsis.

2010 European Federation of Internal Medicine.

Use of non-invasive ventilation in Weaning

Title: Strategies for the withdrawal of nasal continuous positive airway pressure (NCPAP) in

preterm infants.

Citation:  Cochrane  Database  of Systematic  Reviews, 2011,  vol./is.  2/(CD006979),  1361-

6137;1469-493X    (2011)   Author(s):  Jardine   LA,   Inglis    GD,    Davies   MW    Abstract:

BACKGROUND: While indications for the use of nasal continuous positive airway pressure

(NCPAP) and its associated risks and benefits are extensively investigated, the best strategy

for the withdrawal of NCPAP remains unknown. In a survey of Australian and New Zealand

Neonatologists, 56% stated that their approach to NCPAP weaning was "ad hoc" (Jardine

2008). At what point an infant is considered stable enough to attempt to start withdrawing

their NCPAP is not clearly established. The criteria for a failed attempt at NCPAP withdrawal

is also not clear.OBJECTIVES: To determine the risks and benefits of different strategies

used for the withdrawal of NCPAP in preterm infants.SEARCH STRATEGY: Searches were

made of the Cochrane Neonatal Review Group Specialised Register, MEDLINE from 1966

to  June  2010,  CINAHL   from  1982  to  June  2010,  and  the  Cochrane  Central  Register  of

Controlled   Trials   (CENTRAL,    The   Cochrane  Library  2010,  Issue   2).  Previous   reviews

(including  cross references) were also  searched.SELECTION    CRITERIA: We     included  all

randomised and quasi-randomised controlled trials in which either individual newborn infants

or clusters of infants (such as separate neonatal units) were randomised to different NCPAP

withdrawal strategies (from the first time they come off NCPAP and any subsequent weaning

and/or   withdrawal  attempt).DATA   COLLECTION     AND   ANALYSIS:   We   used   standard

methods of The Cochrane Collaboration and its Neonatal Review Group.MAIN RESULTS:

We identified four potentially eligible studies. Three studies are included in this review. One

study showed a significant decrease in the duration of     oxygen therapy and a significantly

decreased  length  of stay for babies  randomised  to  a  weaning strategy where NCPAP   is

simply  stopped  when infants  met  predefined  stability  criteria.AUTHORS'   CONCLUSIONS:

Infants who have their NCPAP pressure weaned to a predefined level and then stop NCPAP

completely  have  less total  time  on  NCPAP   and  shorter durations  of  oxygen therapy  and

hospital stay compared with those that have NCPAP removed for a predetermined number

of hours each day. Future trials of withdrawing NCPAP should compare proposed strategies

with weaning NCPAP pressure to a predefined level and then stopping NCPAP completely.

Clear  criteria  need  to  be  established  for  the  definition  of  stability  prior  to  attempting   to

withdraw NCPAP.Full Text:  Available in fulltext at Wiley

Cell salvage in surgery (including obstetric surgery)

Title:  Coagulopathy   during  intraoperative  cell  salvage  in  a  patient  with  major   obstetric

haemorrhage

Citation:  British  Journal  of  Anaesthesia,  May  2011,  vol./is.  106/5(749),  0007-0912;1471-

6771  (May  2011)  Author(s): Catling   S.,  Haynes  S.L.  Full  Text: Available  in  fulltext  at

EBSCO Host EJS Available in print at Solihull Staff Library

Anaesthesia and Immunomodulation

Nothing to report

Anaesthesia and post operative confusion

Nothing to report

Anaesthesia and surgical outcomes

Title:  Comparison  of analgesic  efficacy of subcostal  transversus abdominis  plane  blocks

with epidural analgesia following upper abdominal surgery

Citation: Anaesthesia, June 2011, vol./is. 66/6(465-471), 0003-2409;1365-2044 (June 2011)

Author(s): Niraj   G.,   Kelkar   A.,  Jeyapalan   I.,   Graff-Baker  P.,   Williams    O.,  Darbar   A.,

Maheshwaran  A.,  Powell   R.   Abstract:  Subcostal   transversus  abdominis   plane   (TAP)

catheters have been reported to be an effective method of providing analgesia after upper

abdominal   surgery. We  compared  their  analgesic  efficacy with that  of epidural  analgesia

after  major   upper  abdominal   surgery  in   a   randomised   controlled   trial.   Adult   patients

undergoing elective open hepatobiliary or renal surgery were randomly allocated to receive

subcostal TAP catheters (n = 29) or epidural analgesia (n = 33), in addition to a standard

postoperative   analgesic   regimen   comprising   of  regular   paracetamol   and   tramadol   as

required.   The   TAP   group   patients   received  bilateral   subcostal  TAP   catheters  and  1

mg.kg^-1 bupivacaine 0.375% bilaterally every 8 h. The epidural group patients

received  an  infusion  of  bupivacaine  0.125%  with fentanyl  2  mug.ml^-1.   The

primary outcome measure was visual analogue pain scores during coughing at 8, 24, 48 and

72  h  after  surgery. We  found  no  significant  differences in  median   (IQR   [range])  visual

analogue scores during coughing at 8 h between the TAP group (4.0 (2.3-6.0 [0-7.5])) and

epidural group (4.0 (2.5-5.3) [0-8.5])) and at 72 h (2.0 (0.8-4.0 [0-5]) and 2.5 (1.0-5.0 [0-6]),

respectively). Tramadol consumption was significantly greater in the TAP group (p = 0.002).

Subcostal  TAP  catheter  boluses  may  be  an  effective alternative  to  epidural  infusions for

providing postoperative analgesia after upper abdominal surgery. 2011 The Association of

Anaesthetists of Great Britain and Ireland.

Title: A double-blind, randomized, multicenter study of MP4OX for treatment of perioperative

hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia

Citation:  Anesthesia and  Analgesia,  April  2011,  vol./is.  112/4(759-773),  0003-2999  (April

2011)  Author(s): Van  Der  Linden  P.,  Gazdzik  T.S.,  Jahoda  D.,  Heylen  R.J.,  Skowronski

J.C., Pellar D., Kofranek I., Gorecki A.Z., Fagrell B., Keipert P.E., Hardiman Y.J., Levy H.

Abstract: Background: MP4OX (oxygenated polyethylene glycol-modified hemoglobin) is a

novel oxygen therapeutic agent specifically developed to perfuse and oxygenate tissue at

risk for ischemia and hypoxia. In this study, we investigated the ability of MP4OX to treat

hypotensive  episodes.  In   addition,   the  tolerability   profile  of  MP4OX   in  a  large  surgical

population was established. Methods: Patients from 21 study sites in 5 countries, scheduled

to undergo primary hip arthroplasty under spinal anesthesia, were randomized in a double-

blind  manner   to  receive  MP4OX   or  hydroxyethyl  starch  (HES)   solution  (Voluven;  HES

130/0.4).  Patients  received  the first  250-mL  dose  of investigational  product  when systolic

blood  pressure decreased  to  the  predefined  dosing  trigger.  A second  250-mL  dose  was

given   only   if  the   systolic  blood   pressure  decreased  to   the   same   trigger   level   after

administration   of  the  first  dose.  The  primary  efficacy outcome  was total  duration  of  all

hypotensive episodes during surgery and the first 6 hours after skin closure. Results: Of the

474 patients randomized, 405 reached the dosing trigger and received at least 1 dose. The

mean total duration of all hypotensive episodes was significantly shorter (P < 0.0001) in the

MP4OX group (52.4 +/- 71.50 minutes; range, 3-442 minutes) compared with the HES group

(137.6 +/- 120.21 minutes; range, 5-435 minutes). The overall incidence of adverse events

(AEs)  in  the  intent-to-treat  population  was similar  between the  MP4OX   and  HES   groups

(75.2%  vs 73.4%;  P  =  0.733).  Transient  increases  in  laboratory  values  were reported  in

more  patients  in  the  MP4OX   group  versus HES   controls  for aspartate  aminotransferase

(13.4% vs 7.4%; P = 0.052), alanine aminotransferase (6.9% vs 4.9%; P = 0.409), lipase

(9.7% vs 3.6%; P = 0.015), and troponin (8.1% vs 2.0%; P = 0.006). There was no significant

difference in the incidence of serious AEs reported (6.4% in MP4OX group vs 3.0% in HES

controls; P = 0.106). Certain AEs did occur more frequently in the MP4OX group, including

nausea (23.8% vs 14.3%; P = 0.016), bradycardia (14.9% vs 5.9%; P = 0.003), hypertension

(8.4% vs 2.5%; P = 0.009), and oliguria (5.9% vs 1.5%; P = 0.019). The composite morbidity

and  ischemia  end  points  did  not  reveal  any  differences between the  2  treatment  groups.

Conclusions:  Administration   of  MP4OX   achieved  the  end  point  of  treating  perioperative

hypotension  in  patients  undergoing  primary  hip  arthroplasty  under  spinal  anesthesia.  The

study was not powered to demonstrate clinical benefit based on the composite morbidity or

ischemia outcomes. Although efficacy end points with sufficient power were met, MP4OX is

not  being  proposed for  use  in  routine  surgery where the  risk-benefit profile  would not  be

favorable   based   on   the   safety  profile   demonstrated   in   this   study.   Copyright   2011

International Anesthesia Research Society. Full Text: Available in fulltext at Ovid