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Critical Care Reviews Newsletter

July 14th 2013



Welcome to the 84th Critical Care Reviews Newsletter, bringing you the best critical care research published in the past week, plus a wide range of free full text review articles and guidelines from over 300 clinical and scientific journals.

It's been another quiet week for critical care research, with no major adult studies being published. The highlight is the latest negative surfactant study, this time in the paediatric setting. There is a pilot study of L-carnitine in septic shock, a meta analysis examining oral decontamination, as well as observational studies into ARDS, perioperative hypotension, and seizure prophylaxis. The future of critical care moves a little closer, with a proof-of-concept study reporting the development of a vascularised and functional human liver from pluripotent stem cells.

There is just one guideline this week, adressing how to utilise the microbiological laboratory to best diagnose infection. Additionally, there are editorials on failed intubation and fluid resuscitation, plus a commentary on medical billing in the USA.

Amongst the clinical review articles are papers on traumatic brain injury, subarachnoid haemorrhage, ketamine, balanced crystalloids, cardiac regeneration, lung injury, asthma, liver disease monitoring, babeiosis, sepsis biomarkers, aspergillus, and surgical decision making. There is one non-clinical review paper on medical writing.

The topic for This Week's Papers is coagulopathy, starting with a paper on trauma-induced coagulopathy in tomorrow's Paper of the Day.



Randomized Controlled Trial

Journal of Parenteral and Enteral Nutrition:     Septic Shock

Puskarich et al completed a phase II double-blind randomized control trial comparing levocarnitine (n=16) with 0.9% saline (n=15) in the management of vasopressor-dependent septic shock. There was no difference in the primary outcome of serious adverse events (L-carnitine 2.1 SAEs vs saline 1.8 SAEs per patient; P = 0.44), or in the secondary efficacy outcome of a decrease of 2 points or more in SOFA score at 24 hours (L-carnitine 53% vs saline 44%; P = 0.59). Interestingly, L-carnitine was associated with a significantly lower 28 day mortality (4/16 vs 9/15; P = 0.048), and a trend for improved survival at 1 year (P=0.06).

Abstract:  Puskarich. Preliminary Safety and Efficacy of L-carnitine Infusion for the Treatment of Vasopressor-Dependent Septic Shock: A Randomized Control Trial. JPEN J Parenter Enteral Nutr 2013;epublished July 12th


Pediatric Critical Care Medicine:     ARDS

Willson and colleagues performed a blinded, randomized, placebo-controlled trial investigating calfactant, an exogenous surfactant derived from calf surfactant, in paediatric ARDS. The trial was stopped for futility after the second interim analysis, with 110 patients recruited. There was no effect on oxygenation, mortality (calfactant group 7 deaths versus placebo group 5 deaths), or other endpoints, apart from a reduction in hospital free days with the intervention (10.4 +/- 7.8 placebo vs 6.4 +/- 7.8 surfactant; p = 0.01).

Abstract:  Willson. Pediatric Calfactant in Acute Respiratory Distress Syndrome Trial. Pediatr Crit Care Med 2013;epublished July 10th


Systematic Review and Meta Analysis

Journal of Hospital Infection:     Oral Decontamination

In a systematic review and meta analysis, comprising 16 trials and 2,399 patients, oral topical antiseptics significantly reduced the incidence of ventilator-associated pneumonia (risk ratio 0.66; 95% CI 0.49–0.88) in adult patients receiving mechanical ventilation for more than 48hours. Excluding studies using iseganan, antibiotics also demonstrated a reduced incidence of VAP (RR: 0.27; 95% CI: 0.18–0.42). Neither antiseptics nor antibiotics affected all-cause mortality, duration of ventilation, or duration of intensive care unit stay.

Abstract:  Li. Oral topical decontamination for preventing ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials. J Hosp Infect 2013;epublished July 8th


Prospective Observational Study

The Lancet Respiratory Medicine:     ARDS

In a prospective observational study, comprising autopsy data from 159 patients with histologically confirmed ARDS, Thille et al sought to determine the chronology of histological lesions in ARDS. Exudative changes occurred early in the course of ARDS and decreased over time, being present in 90% (74/82) of patients with ARDS < 1 week duration, 74% (40/54) with disease of 1—3 week duration, and only 17% (4/23) with disease > 3 weeks' duration (p<0·0001). Proliferative changes occurred in an opposite manner and increased over time, being present in 54% (44/82) of patients with ARDS < 1-week duration, 78% (42/54) with disease duration of 1—3 weeks, and 100% (n=23) with disease duration > 3 weeks (p<0·0001). Fibrosis occurred in a similar manner, being present in 4% (3/82) with ARDS of < 1 weeks duration, 24% (13/54) with ARDS of 1—3-weeks' duration, and 61% (14/23) with ARDS > 3-week duration (p<0·0001). Also, patients with ARDS of pulmonary origin, in comparison to those with ARDS of non-pulmonary origin, more frequently had fibrosis.

Abstract:  Thille. Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies. Lancet Respiratory Medicine 2013;1(5):395-401


Journal of Trauma and Acute Care Surgery:     Seizure Prophylaxis

Inaba completed a two-centre observational study, comparing levetiracetam with phenytoin for early seizure prophylaxis in 813 patients with traumatic brain injury, with choice of therapy being determined by local protocol. Both groups were similar in profile. There was no difference in seizure rate (1.5% vs.1.5%; P = 0.997), adverse drug events (7.9% vs. 10.3%;, P = 0.227), or mortality (5.4% vs. 3.7%; P = 0.236).

Abstract:  Inaba. A prospective multicenter comparison of levetiracetam versus phenytoin for early posttraumatic seizure prophylaxis. J Trauma Acute Care Surg 2013;74(3):766-71


Nature:     Liver Engineering

Takebe report a proof-of-concept study demonstrating the in vitro growth of a vascularized human liver from human induced pleuripotent stem cells. The organ was functional, producing proteins and metabolising human-specific drug.

Abstract:  Takebe. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013;epublished July 3rd 


Retrospective Observational Study

Anesthesiology:     Intra-Operative Hypotension

Using perioperative data from 33,330 noncardiac surgeries at the Cleveland Clinic, Ohio, USA, Walsh and colleagues sought to examine the relationship between intraoperative hypotension (mean arterial pressure < 55 to 75 mmHg) and postoperative acute kidney injury and myocardial injury. AKI and myocardial injury developed in 2,478 (7.4%) and 770 (2.3%) surgeries, respectively, with a MAP threshold where the risk for both outcomes increased being less than 55 mmHg. The greater the duration of hypotension < 55 mmHg, the greater the risk of acute kidney injury and/or myocardial infarction.

Abstract:  Walsh. Relationship between Intraoperative Mean Arterial Pressure and Clinical Outcomes after Noncardiac Surgery: Toward an Empirical Definition of Hypotension. Anesthesiology 2013;epublished July 3rd


JAMA Neurology:     Stroke Thrombolysis

Using data on 29,618 patients from the Stroke International Stroke Thrombolysis Register (SITS-ISTR), Ahmed et al compared the outcomes of patients with acute ischaemic stroke, and treated with intravenous thrombolysis with alteplase, based on whether this therapy was administered within 3 hours (85.4%), 3 to 4.5 hours (13.7%) or 4.5 to 6 hours (1%) after stroke onset. There was no difference between groups with respect to incidence of symptomatic intracerebral hemorrhage (within 3 hours: 1.5%, 3 - 4.5 hours: 1.8%, 4.5 - 6 hours: 2.6%), functional independence at 3 months (within 3 hours: 58.4%, 3 - 4.5 hours: 62.7%, 4.5 - 6 hours: 61.3%), or mortality at 3 months (within 3 hours: 11.8%, 3 - 4.5 hours: 11.1%, 4.5 - 6 hours: 11.8%).

Abstract:  Ahmed. Results of Intravenous Thrombolysis Within 4.5 to 6 Hours and Updated Results Within 3 to 4.5 Hours of Onset of Acute Ischemic Stroke Recorded in the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis Register (SITS-ISTR). An Observational Study. JAMA Neurol 2013;70(7):837-844


JAMA Internal Medicine:     Cardiac Arrest

In a large national registry study including 102,153 cases from 358 hospitals, Chen and colleagues aimed to describe the association between inpatient cardiac arrest incidence and survival. The median hospital cardiac arrest incidence was 4.02 per 1000 admissions (IQR 2.95-5.65 per 1000 admissions), with a median hospital case-survival rate of 18.8% (IQR 14.5%-22.6%). In crude analyses, hospitals with higher case-survival rates also had lower cardiac arrest incidence (r, −0.16; P = .003), with this association persisting after adjusting for patient characteristics (r, −0.15; P  = 0 .004), but not after adjusting for hospital characteristics (r −0.07; P = 0.18). The modifiable hospital factor that most attenuated this relationship was a hospital’s nurse-to-bed ratio (r −0.12; I = 0.03).

Abstract:  Chen. Association Between a Hospital’s Rate of Cardiac Arrest Incidence and Cardiac Arrest Survival. JAMA Intern Med. 2013;173(13):1186


Preclinical Study

Nature:     Liver Engineering

Takebe report a proof-of-concept study demonstrating the in vitro growth of a vascularized human liver from human induced pleuripotent stem cells. The organ was functional, producing proteins and metabolising human-specific drug.

Abstract:  Takebe. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 2013;epublished July 3rd 




Anaesthesia:     Failed Intubation


Current Opinion in Critical Care:     Fluid Resuscitation



Journal of the American Medical Association:     Medical Billing


Review - Clinical


Annals of Intensive Care:     Traumatic Brain Injury


NeuroRehabilitation:     Neuroimaging post Critical Illness

Anesthesiology Clinics:     Traumatic Brain Injury


Current Opinion in Critical Care:     Crystalloids


Journal of Cellular and Molecular Medicine:     Cardiac Regeneration


Research Reports in Clinical Cardiology:     Coronary Artery Disease


ANZ Journal of Surgery:     Aortacaval Fistula


Pharmaceuticals:     Congestive Heart Failure



Journal of Cellular and Molecular Medicine:     Acute Lung Injury

International Journal of General Medicine:     Asthma


Pulmonary Circulation:    Chronic Thromboembolic Pulmonary Hypertension


International Journal of Nutrition, Pharmacology and Neurological Disorders:     Probiotics



Liver International:     Coagulation Tests in Liver Disease



Core Evidence:     Lixivaptan


American Journal of Nephrology:     Electrolyte Disorders





Journal of the American Heart Association:     Testosterone



Journal of Clinical Investigation:     Mitochondria



PLoS Pathogens:     Babeiosis


Vascular Health and Risk Management:     Dabigatran



Annals of Intensive Care:     Sepsis Biomarkers


Journal of Antimicrobial Chemotherapy:     Aspergillus



International Journal of Research in Pharmacy and Science:     Sepsis



ANZ Journal of Surgery:     Limb Reconstruction



Nursing Research and Practice:     Epigenetics


International Journal of Inflammation:     Metabolic Acidosis


ANZ Journal of Surgery:     Surgical Decision Making


Review - Non-Clinical

ANZ Journal of Surgery:     Medical Writing



I hope you find these brief summaries and links useful.

Until next week