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, PaO<sub>2</sub>/fraction of inspired oxygen (FiO<sub>2</sub>) 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
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Anaesthesia and post operative confusion
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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<sup>-1</sup> bupivacaine 0.375% bilaterally every 8 h. The epidural group patients
received an infusion of bupivacaine 0.125% with fentanyl 2 mug.ml<sup>-1</sup>. 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
Cardiac arrests/cardiopulmonary resuscitation –quality of CPR; use
of feedback devices; leadership and team factors
Title: Delivering high-quality cardiopulmonary resuscitation in-hospital
Citation: Current Opinion in Critical Care, June 2011, vol./is. 17/3(225-230), 1070-
5295;1531-7072 (June 2011) Author(s): Soar J., Edelson D.P., Perkins G.D. Abstract:
Purpose of review: This review discusses recent data relating to delivering high-quality
cardiopulmonary resuscitation (CPR) to patients with in-hospital cardiac arrest. Recent
findings: Delivering high-quality CPR requires interventions at a national, local, team and
individual rescuer level. These include measuring patient outcomes, patient safety incident
reporting, education, an increased emphasis on human factors, briefing and debriefing of
resuscitation teams, and the use of sensing devices that provide real-time prompts or
feedback to rescuers during CPR. Data from national registries, patient safety incident
reports and mock codes can be used to identify areas for improving practice. Education of
staff is essential in both technical and nontechnical resuscitation skills (human factors).
Resuscitation team performance can be improved by ensuring teams brief and plan
beforehand and also debrief using feedback data collected during resuscitation events. The
use of feedback and prompt devices helps improve adherence to guidelines for chest
compression quality but data are lacking in terms of showing improved patient outcomes.
Summary: Delivering high-quality CPR in-hospital requires a multifaceted approach.
Collecting data during arrests and feeding back in real time and postevent during debriefings
can be used to improve delivery of high-quality CPR. There are few studies that show
improvement in actual patient outcomes (e.g., survival to hospital discharge) with
improvements in delivery of high-quality CPR. Recognizing the importance of both technical
and nontechnical skills (human factors) to deliver high-quality CPR is essential.
Title: Measure and improve
Citation: Resuscitation, June 2011, vol./is. 82/6(645-646), 0300-9572;1873-1570 (June
2011) Author(s): Kwok H., Rea T. Full Text: Available in fulltext at Elsevier; Note: You will
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