ICU Pharmacists e-Group
UKCPA-Critical Care
Hosted by www.ukcpa.net
Critical Care Journal Club Bulletin
June 2012
Selected Bottom Lines:  Hydroxyethyl starch 130/0.4 vs. Ringer's acetate in severe sepsis: RCT
N Engl J Med 366 (26): 27 June 2012
No stars = Paper highlighted for general interest (read only if of particular interest or relevance to you)
One star = Highlighted paper of particular note with relevance to most ICU pharmacists (should be read)
Two stars = Ground breaking or keynote paper of direct relevance to all (essential reading for all ICU pharmacists)
Collated By Nic Rudall
Contributions
“Mild therapeutic hypothermia in cardiogenic shock syndrome.”
Zobel, Carsten et al.
Crit Care 40 (6): 1715-1723
“An observational study fluid balance and patient outcomes in the randomized
evaluation of normal vs. augmented level of replacement therapy trial.”
The RENAL Replacement Therapy Study Investigators
Crit Care 40 (6): 1753-1760
“Acetyl salicylic acid usage and mortality in critically ill patients with the systemic
inflammatory response syndrome and sepsis.”
Eisen, Damon P. et al.
Crit Care 40 (6): 1761-1767
“Relationship between systemic glucose and cerebral glucose is preserved in patients
with severe traumatic brain injury, but glucose delivery to the brain may become
limited when oxidative metabolism is impaired: Implications for glycemic control.”
Magnoni, Sandra et al.
Crit Care 40 (6): 1785-1791
“Isoflurane delays the development of early brain injury after subarachnoid
hemorrhage through sphingosine-related pathway activation in mice.”
Altay, Orhan et al.
Crit Care 40 (6): 1908-1913
“Factors influencing intracranial pressure monitoring guideline compliance and
outcome after severe traumatic brain injury.”
Biersteker, Heleen A.R. et al.
Crit Care 40 (6): 1914-1922
“Tight glycemic control increases metabolic distress in traumatic brain injury: A
randomized controlled within-subjects trial.”
Vespa, Paul et al.
Crit Care 40 (6): 1923-1929
“Treatment of acute coronary syndrome: Part 2: ST-segment elevation myocardial
infarction.”
Trost, Jeffrey C. et al.
Review
Crit Care 40 (6): 1939-1945
“Delirium screening in critically ill patients: A systematic review and meta-analysis.”
Neto, Ary Serpa et al.
Review
Crit Care 40 (6): 1946-1951
Contributed by Louise Potts, Newcastle Upon Tyne Hospitals NHS Trust, 6/7/2012
Time for change: traditional audit or continuous improvement?
C. Farrell and D. Hill
Anaesthesia 67 (7): 699-702
Bottom line: Editorial suggesting healthcare systems would make better progress by
embracing continuous improvement methods (repeated small changes on small
samples) rather than traditional audit cycles, which require large numbers and time to
evaluate.
Review of patient safety incidents reported from critical care units in North-West
England in 2009 and 2010
A. N. Thomas and R. J. Taylor
Anaesthesia 67 (7): 706-713
Bottom line: “Medications” was one of the most frequent classifications for reported
errors, though the paper makes little reference to the detailed problems other than
highlighting the continued occurrence of glucose infusions in arterial lines.
Non-Luer connectors: are we nearly there yet?
T. M. Cook
Anaesthesia 67 (7): 784-792
Bottom line: Update on the progress towards the introduction of these connectors. Still
several problems to overcome, and a slipping timescale, but getting there!
Contributed by Alan Timmins, NHS Fife, 2/7/12
Hydroxyethyl starch 130/0.4 vs. Ringer's acetate in severe sepsis: RCT
Perner, A. et al
N Engl J Med 366 (26): 27 June 2012
Contributed by Annie Bell, Nelson, 2/7/2012
Reviews and Resources Available on the Internet
NATIONAL ELECTRONIC LIBRARY FOR MEDICINES
Statin therapy in critical illness: an international survey of intensive care
physicians' opinions, attitudes and practice
Original article by: M Shankar Hari, PS Kruger, S Di Gangi, DC Scales, GD Perkins, DF McAuley, M
Terblanche
Reference: BMC Clinical Pharmacology 28 Jun 2012;12:13
Source: BMC Clinical Pharmacology
Keywords: Atorvastatin; Attitude; Australia; Critical Care; Drug Utilisation; HMG-CoA Reductase Inhibitors;
Intensive Care Unit; New Zealand; Prescribing Patterns; Sepsis; Simvastatin; United Kingdom;
Date published: 29/06/2012 08:50
Summary
by: Pharm-line
Background: Pleotropic effects of statins on inflammation are hypothesised to attenuate the severity of and
possibly prevent the occurrence of the host inflammatory response to pathogen and infection-related acute
organ failure. We conducted an international survey of intensive care physicians in Australia, New Zealand
(ANZ) and the United Kingdom (UK). The aims of the survey were to assess the current prescribing practice
patterns, attitudes towards prescribing statin therapy in critically ill patients and opinions on the need for an
interventional trial of statin therapy in critically ill patients.
Methods: Survey questions were developed through an iterative process. An expert group reviewed the
resulting 26 items for face and content validity and clarity. The questions were further refined following pilot
testing by ICU physicians from Australia, Canada and the UK. We used the online Smart Survey software to
administer the survey.
Results: Of 239 respondents (62 from ANZ and 177 from UK) 58% worked in teaching hospitals; most
(78.2%) practised in 'closed' units with a mixed medical and surgical case mix (71.0%). The most frequently
prescribed statins were simvastatin (77.6%) in the UK and atorvastatin (66.1%) in ANZ. The main reasons
cited to explain the choice of statin were pre-admission prescription and pharmacy availability. Most
respondents reported never starting statins to prevent (65.3%) or treat (89.1%) organ dysfunction. Only a
minority (10%) disagreed with a statement that the risks of major side effects of statins when prescribed in
critically ill patients were low. The majority (84.5%) of respondents strongly agreed that a clinical trial of
statins for prevention is needed. More than half (56.5%) favoured rates of organ failure as the primary
outcome for such a trial, while a minority (40.6%) favoured mortality.
Conclusions: Despite differences in type of statins prescribed, critical care physicians in the UK and ANZ
reported similar prescription practices. Respondents from both communities agreed that a trial is needed to
test whether statins can prevent the onset of new organ failure in patients with sepsis.
Clinical Review: Ventilator associated pneumonia
Reference: BMJ 2012; 344: e3325
Source: BMJ
Date published: 01/06/2012 16:40
Summary
by: Yuet Wan
Ventilator associated pneumonia is the most common healthcare associated infection in intensive care and
is
associated
with
increased
morbidity,
mortality,
length
of
stay,
and
costs
This review covers the following questions and topics:
• What causes ventilator associated pneumonia?
• What are the risk factors for developing ventilator associated pneumonia?
• How is ventilator associated pneumonia diagnosed?
• Which organisms are associated with ventilator associated pneumonia?
• Which antibiotics are used to treat ventilator associated pneumonia?
• Can ventilator associated pneumonia be prevented?
Review: Carbapenem antibiotics for serious infections
Reference: BMJ 2012; 344: e3236
Source: BMJ
Date published: 01/06/2012 16:42
Summary
by: Yuet Wan
This review in the BMJ on carbapenem antibiotics begins with a case vignette and then addresses the
following questions:
• What are carbapenems?
• How well do carbapenems work?
• How safe are carbapenems?
• What are the precautions?
• How cost effective are carbapenems?
• How are carbapenems taken and monitored?
• How do carbapenems compare with other antibiotics?
SMC accepts dexmedetomidine (Dexdor®) for sedation in adult intensive
care unit (ICU) patients
Source: Scottish Medicines Consortium (SMC)
Date published: 12/06/2012 14:42
Summary
by: Hina Radia
The Scottish Medicines Consortium (SMC) has accepted dexmedetomidine (Dexdor®) for use within NHS
Scotland for sedation in adult intensive care unit (ICU) patients requiring a sedation level not deeper than
arousal in response to verbal stimulation (corresponding to Richmond Agitation-Sedation Scale [RASS] 0 to
-3).
The Committee noted that dexmedetomidine was as effective as propofol and midazolam in maintaining the
target depth of sedation in ICU patients. The median duration of mechanical ventilation was numerically
shorter with dexmedetomidine than with propofol and significantly shorter than with midazolam.
RCT: Effect of empirical treatment with moxifloxacin and meropenem vs.
meropenem on sepsis-related organ dysfunction
Reference: JAMA published early online on 13 June 2012
Source: JAMA
Date published: 13/06/2012 17:04
Summary
by: Hina Radia
According to research published in the Journal of the American Medical Association, among adults with
severe sepsis, treatment with combined meropenem and moxifloxacin compared with meropenem alone
does not result in less organ failure.
Early appropriate antimicrobial therapy leads to lower mortality rates associated with severe sepsis. The role
of empirical combination therapy comprising at least 2 antibiotics of different mechanisms remains
controversial, and this randomised controlled trial was conducted to compare the effect of moxifloxacin in
combination with meropenem, with the effect of meropenem alone on sepsis-related organ dysfunction.
The open-label parallel group trial involved 600 patients who fulfilled criteria for severe sepsis or septic
shock who received monotherapy with moxifloxacin 400 mg every 24 hours (n=298) or combination therapy
with meropenem 1g every 8 hours and moxifloxacin 400mg every 24 hours (n=302). The trial was
performed at 44 intensive care units in Germany from October 16, 2007, to March 23, 2010. The number of
evaluable patients was 273 in the monotherapy group and 278 in the combination therapy group. The
intervention was recommended for 7 days and up to a maximum of 14 days after randomisation or until
discharge from the intensive care unit or death, whichever occurred first.
The primary outcome measure was degree of organ failure (mean of daily total Sequential Organ Failure
Assessment [SOFA] scores over 14 days; score range: 0-24 points with higher scores indicating worse
organ failure), Secondary outcome included 28-day and 90-day all-cause mortality. Survivors were followed
up for 90 days. The following results were reported:
• There was no statistically significant difference in mean SOFA scores between the meropenem and
moxifloxacin group (8.3 points; 95% CI, 7.8-8.8 points) and the meropenem alone group (7.9 points; 7.5-8.4
points) (P = 0.36).
• By day 28, there were 66 deaths (23.9%; 19.0%-29.4%) in the combination therapy group compared with
59 deaths (21.9%; 17.1%-27.4%) in the monotherapy group (P = 0.58).
• By day 90, there were 96 deaths (35.3%; 29.6%-41.3%) in the combination therapy group compared with
84 deaths (32.1%; 26.5%-38.1%) in the monotherapy group (P = 0.43).
• At least 1 adverse event occurred in 85 patients (28.1% 23.1%-33.5%]) in the combination therapy group
and in 71 patients (24.2% [19.4%- 29.6%]) in the monotherapy group (P=0.31).
The researchers conclude by highlighting several limitations of the study, although state that no beneficial
effect of combination therapy including meropenem and moxifloxacin with regard to the 14- day mean SOFA
score, or with regard to any secondary end point was observed.
Presence and accuracy of drug dosage recommendations for continuous
renal replacement therapy in tertiary drug information references
Original article by: SK Gorman, RS Slavik, S Lam
Reference: Canadian Journal of Hospital Pharmacy Jun 2012;65(3):
Source: Canadian Journal of Hospital Pharmacy
Keywords: Accuracy; Databases; Dose Calculation; Drug Administration Schedule; Haemodialysis; Kidney
Function-Impaired; Reference Books;
Date published: 25/06/2012 11:17
Summary
by: Pharm-line
Background: Clinicians commonly rely on tertiary drug information references to guide drug dosages for
patients who are receiving continuous renal replacement therapy (CRRT). It is unknown whether the
dosage recommendations in these frequently used references reflect the most current evidence.
Objective: To determine the presence and accuracy of drug dosage recommendations for patients
undergoing CRRT in 4 drug information references.
Methods: Medications commonly prescribed during CRRT were identified from an institutional medication
inventory database, and evidence-based dosage recommendations for this setting were developed from the
primary and secondary literature. The American Hospital Formulary System-Drug Information (AHFS–DI),
Micromedex 2.0 (specifically the DRUGDEX and Martindale databases) and the 5th edition of Drug
Prescribing in Renal Failure (DPRF5) were assessed for the presence of drug dosage recommendations in
the CRRT setting. The dosage recommendations in these tertiary references were compared with the
recommendations derived from the primary and secondary literature to determine concordance.
Results: Evidence-based drug dosage recommendations were developed for 33 medications administered in
patients undergoing CRRT. The AHFS-DI provided no dosage recommendations specific to CRRT,
whereas the DPRF5 provided recommendations for 27 (82%) of the medications and the Micromedex 2.0
application for 20 (61%) (13 (39%) in the DRUGDEX database and 16 (48%) in the Martindale database,
with 9 medications covered by both). The dosage recommendations were in concordance with evidencebased recommendations for 12 (92%) of the 13 medications in the DRUGDEX database, 26 (96%) of the 27
in the DPRF5 and all 16 (100%) of those in the Martindale database.
Conclusions: One prominent tertiary drug information resource provided no drug dosage recommendations
for patients undergoing CRRT. However, 2 of the databases in an Internet-based medical information
application and the latest edition of a renal specialty drug information resource provided recommendations
for a majority of the medications investigated. Most dosage recommendations were similar to those derived
from the primary and secondary literature. The most recent edition of the DPRF is the preferred source of
information when prescribing dosage regimens for patients receiving CRRT.
Hydroxyethyl starch 130/0.4 vs. Ringer's acetate in severe sepsis: RCT
Reference: N Engl J Med published online 27 June 2012
Source: New England Journal of Medicine
Date published: 28/06/2012 18:43
Summary
by: Yuet Wan
Hydroxyethyl starch (HES) 130/0.4 is widely used for fluid resuscitation in intensive care units (ICUs), but its
safety and efficacy have not been established in patients with severe sepsis. The 6S Trial Group and the
Scandinavian Critical Care Trials Group conducted a multicentre, parallel-group, blinded trial to compare
fluid resuscitation in the ICU with 6% HES 130/0.4 or Ringer’s acetate (up to 33 ml/kg/day) in 804 such
patients. The primary outcome measure was either death or end-stage kidney failure (dependence on
dialysis) at 90 days after randomisation.
At 90 days after randomisation, 798 were included in the modified intention-to-treat population, and the
following findings reported:
• 201 of 398 patients (51%) assigned to HES 130/0.4 had died, vs. 172 of 400 patients (43%) receiving
Ringer’s acetate (relative risk, 1.17; 95% CI, 1.01 to 1.36; p = 0.03); 1 patient in each group had end-stage
kidney failure.
• 87 patients (22%) assigned to HES 130/0.4 were treated with renal-replacement therapy vs. 65 patients
(16%) assigned to Ringer’s acetate (1.35, 1.01 to 1.80; p = 0.04)
• 38 patients (10%) and 25 patients (6%) on HES and Ringer’s acetate, respectively, had severe bleeding
(1.52; 0.94 to 2.48; p = 0.09).
• The results were supported by multivariate analyses, with adjustment for known risk factors for death or
acute kidney injury at baseline.
The researchers conclude from these findings that “patients with severe sepsis assigned to fluid
resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require
renal-replacement therapy, as compared with those receiving Ringer’s acetate.”
List of Contributors
Contributor
Nicola Rudall
Newcastle Upon Tyne Hospitals NHS
Foundation
Trust,
Nicola.Rudall@nuth.nhs.uk
Andrew Turton
Princes Royal University hospital
andrew.turton@nhs.net
Jennifer Murphy
Wishaw General Hospital, Lanarkshire
jennifer.murphy@lanarkshire.scot.nhs.
uk
Caroline Hamilton
Derby Hospitals NHSF Trust
c.hamilton18@tiscali.co.uk
Olivia Moswela
Radcliffe Infirmary
olivia.moswela@orh.nhs.uk
Patricia Ging
MMUH
patriciaging@eircom.net
Journal
Critical
Medicine
Intensive
Medicine
Care
Care
American Journal of
Respiratory
and
Critical Care (First
Fortnight)
American Journal of
Respiratory
and
Critical Care (Second
Fortnight) and
Neurosciences
journals
New England Journal
of Medicine
Mark Borthwick
Oxford Radcliffe Hospitals
mark.borthwick@orh.nhs.uk
Circulation
Internet Resources
Emma Graham-Clarke
Sandwell and West Birmingham
Hospitals NHS Trust
Birmingham
emma.graham-clarke@swbh.nhs.uk
Jane Hylands
Wrightington, Wigan and Leigh NHS
Trust
jhylands@fsmail.net
Lancet (Weekly)
(+ Key articles from
clinical nutrition and
e-SPEN)
JAMA (weekly)
Contributor
Annie Egan
Nelson Hospital, NZ
annie_egan2000@hotmail.com
Journal
Critical Care
David Sapsford
West Suffolk Hospital NHS Trust
david.sapsford@wsh.nhs.uk
British
Journal
Anaesthesia
Clare Crowley
Oxford Radcliffe Hospitals
clare.crowley@orh.nhs.uk
Hospital Pharmacy
Quality and Safety in
Healthcare
John Dade
St. James's University Hospital
john.dade@leedsth.nhs.uk
Thorax
Andreas Fischer
Royal Brompton & Harefield. NHS
Trust
A.Fischer@rbht.nhs.uk
Alan Timmins
Queen Margaret Hospital
alan.timmins@nhs.net
Chest
Philip Moore
Bradford Teaching Hospitals NHS
Trust
philip.moore@bradfordhospitals.nhs.
uk
Chris Jay
Hutt Valley Hospital, NZ
chris.jay@huttvalleydhb.org.nz
Anaesthesia
Analgesia
of
Anaesthesia
The
Annals
Pharmacotherapy
Jan Forlow
BMJ (Weekly)
Jane Sheldon
Anaesthesia
North Cumbria Acute Hospitals NHS
Stockport NHS Foundation Trust
Intensive Care
Trust
Jane.Sheldon@stockport.nhs.uk
jan.forlow@ncumbria-acute.nhs.uk
(List last updated 28st May 2010)
This bulletin would not be possible without the valuable help of volunteer contributors. If there is a
journal, article or resource that you would like to contribute a précis for, or just make the newsgroup
aware of, then please e-mail emma.graham-clarke@swbh.nhs.uk
Next Bulletin scheduled to go out on: Friday 27th August 2010 and will be collated
by: Mark Borthwick: mark.borthwick@orh.nhs.uk
and
of
and