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Critical Care Reviews Newsletter

August 19th 2013



Welcome to the 89th 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.

This week's research studies include interventional studies on magnesium therapy for subarachnoid haemorrhage, restrictive transfusion practice, vasopressors for hepatorenal syndrome, and an intriguing study challenging the dogma of avoiding beta blockade during vasopressor therapy. There are meta analyses on cardiac arrest anti-dysrhythmics, colloid fluid resuscitation, noninvasive ventilation post extubation and extracorporeal membrane oxygenation. Observational studies include investigations into oxygenation during COPD and coma progostication. This week I've changed the way the data are presented in an effort to make it clearer to read.

This week's guidelines address regional anaesthesia during coagulopathy, post cardiac arrest PCI and endovascular therapy for cerebrovascular disease. There are editorials on the speciality of critical care, lung transplantation allocation, post-operative nausea and vomiting, and plagiarism, as well as commentaries on thrombocytopaenia, spinal cord injury and the definition of death.

Amongst the clinical review articles are papers on neurophysiological monitoring, traumatic brain injury, crystalloid fluid therapy, heart-lung interactions, pharmacological management of ARDS, airway ultrasound, GI bleeding, cardiorenal syndrome, ICU skin conditions, and a review paper on major recent studies. Two basic science papers, each with a commentary, report on cardiac engineering and functional activity in the dying brain. There are non-clinical review articles on teaching and open educational resources.

The topic for This Week's Papers is severe hypoxaemic respiratory failure, starting with the first article of a two-part series from Chest, in today's Paper of the Day.



Randomized Controlled Trials

Critical Care Resuscitation:     Subarachnoid Haemorrhage

Bradford et al randomized 162 patients within 72 hours of aneurysmal SAH to either a high serum magnesium concentration (n=81; 1.60-2.50 mmol/L) or a low concentration (n=81; 0.65-1.05 mmol/L) and determined

  1. high concentration therapy was associated with a non-significant reduction in the rate of angiographically confirmed cerebral arterial vasospasm (50.6% versus 64.1%; adjusted OR 0.51; 95% CI 0.26-1.02; P = 0.06).
  2. no difference in neurological recovery between groups
  3. patients treated with high concentration therapy required more noradrenaline and had lower serum calcium concentrations (1.9 [0.2] mmol/L v 2.1 [0.2] mmol/L, P < 0.001).

Abstract:  Bradford. A randomised controlled trial of induced hypermagnesaemia following aneurysmal subarachnoid haemorrhage. Crit Care Resusc 2013;15(2):119-25


Critical Care Medicine:     Restrictive Transfusion

In a parallel-group randomized multicenter pilot trial, Walsh et al compared a restrictive (Hb trigger 70 g/L; target 71-90 g/L) with a liberal (Hb trigger 90 g/L; target 91-110 g/L) blood transfusion strategy to treat anemic (Hb ≤ 90 g/L) critically ill patients aged ≥ 55 years and requiring ≤4 days of mechanical ventilation and found:

  1. the restrictive group had a lower mean Hb concentration ( 81.9 (SD 5.1) versus 95.7 (SD 6.3) g/L), with 21.6% fewer patients being transfused postrandomization (p < 0.001).
  2. this group also received a median of 1 fewer RBC units (95% CI 1-2; p = 0.002).
  3. there were no major differences in organ dysfunction, duration of ventilation, infections, or cardiovascular complications during intensive care or hospital follow-up.
  4. mortality at 180 days post randomization trended toward higher rates in the liberal group (55%) than in the restrictive group (37%), (RR 0.68, 95% CI 0.44-1.05; p = 0.073).

Abstract:  Walsh. Restrictive Versus Liberal Transfusion Strategies for Older Mechanically Ventilated Critically Ill Patients: A Randomized Pilot Trial (RELIEVE Study). Crit Care Med 2013;epublished August 9th


Critical Care Medicine:     Beta Blockade in Septic Shock

In a single-centre, prospective, observational study, in 25 tachycardic patients (heart rate >95 bpm) suffering from septic shock and requiring norepinephrine to maintain mean arterial pressure ≥ 65 mm Hg, and 24 hours after initial hemodynamic optimization, Morelli and colleagues titrated an esmolol infusion to maintain heart rate less than 95 bpm and reported:

  1. heart rate reduced to between 80 and 94 bpm in all patients.
  2. comparing measurements at baseline and 24 hours after esmolol administration, selective β blockade was associated with a decrease in cardiac index (4.0 [3.5; 5.3] vs 3.1 [2.6; 3.9] L/min/m2; p < 0.001), without a change in stroke volume (34 [37; 47] vs 40 [31; 46] mL/beat/m2; p = 0.32), an increase in microcirculatory small vessel blood flow (2.8 [2.6; 3.0] vs 3.0 [3.0; 3.0]; p = 0.002), increases in PaO2 and pH (both p < 0.05), plus a decrease in PaCO2 (p < 0.05).
  3. noradrenaline requirements were significantly reduced (0.53 [0.29; 0.96] vs 0.41 [0.22; 0.79] μg/kg/min; p = 0.03).

Abstract: Morelli. Microvascular Effects of Heart Rate Control With Esmolol in Patients With Septic Shock: A Pilot Study. Crit Care Med 2013;epublished July 18th


Lancet:     Ischaemic Preconditioning & CABG

In a single-centre, double-blind, randomised controlled trial, in 329 patients undergoing elective isolated first-time CABG under cold crystalloid cardioplegia and cardiopulmonary bypass, patients who received remote ischaemic preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia), in contrast to no ischaemic preconditioning (control):

  1. had reduced myocardial injury, as evidence by a lesser cardiac toponin I concentration at 72 hours (266 ng/mL (95% CI 237—298) versus 321 ng/mL (287—360); intention-to-treat population RR 0·83 (95% CI 0·70—0·97, p=0·022); per-protocol analysis RR 0·79, (95% CI 0·66—0·94, p=0·001).
  2. reduced all-cause mortality at 1·5 years with remote ischaemic preconditioning (RR 0·27, 95% CI 0·08—0·98, p=0·046).

Abstract:  Thielman. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 2013;382(9892):597-604    


Lancet:     STEMI

In a secondary, prespecified analysis of the TRILOGY ACS trial (n=7243), a large international multi-centre evaluating whether aspirin plus prasugrel was superior to aspirin plus clopidogrel for long-term therapy in patients with non-ST-segment elevation acute coronary syndrome who did not undergo revascularization, Wivott et al assessed outcomes based on whether or not patients had coronary angiography before anti-platelet treatment and showed:

  1. the 3085 (43%) patients who had angiography at baseline, in comparison with the 4158 (57%) who had not, fewer patients reached the primary composite endpoint of cardiovascular death, myocardial infarction, or stroke at 30 months (281/3085 [12·8%] versus 480/4158 [16·5%], adjusted hazard ratio 0·63, 95% CI 0·53—0·75; p<0·0001);
  2. in those who underwent angiography, fewer prasugrel treated patients reached the primary endpoint (122/1524 [10·7%] versus 159/1561 [14·9%], HR 0·77, 95% CI 0·61—0·98; p=0·032);
  3. in those who did not undergo angiography, there was no difference in outcome between the 2 antiplatelet agents (242/2096 [16·3%] versus 238/2062 [16·7%], HR 1·01, 0·84—1·20; p=0·94)
  4. bleeding tended to be nonsignificantly higher with prasugrel

Abstract:  Wivott. Prasugrel versus clopidogrel for patients with unstable angina or non-ST-segment elevation myocardial infarction with or without angiography: a secondary, prespecified analysis of the TRILOGY ACS trial. Lancet 2013;382(9892):605 - 613    


Liver International:     Hepatorenal Syndrome

In a single-centre, randomized pilot study comparing noradrenaline (n=23) with terlipressin (n=23)  in the treatment of type 2 hepatorenal syndrome, Ghosh and colleagues showed:

  1. There was no difference in reversal of hepatorenal syndrome (n=17 (73.9%) each group, p=1.0)
  2. There was no difference in 90 day mortality (terlipressin 8 deaths versus noradrenaline 9 deaths; p> 0.05)
  3. Noradrenaline was less expensive
  4. There were no major adverse effects
Abstract:  Ghosh. Noradrenaline vs terlipressin in the treatment of type 2 hepatorenal syndrome: a randomized pilot study. Liver Int 2013:33:1187–1193

Annals of Surgery:     Cholecystectomy Timing

In a multicentre, randomized, prospective, open-label, parallel group trial, in 618 patients with acute cholecystitis, comparing early laparoscopic cholecystectomy shortly after hospital admission (n=304) with delayed elective laparoscopic cholecystectomy after a conservative treatment with antibiotics (moxifloxacin), Carsten et al demonstrated superiority with the immediate surgery approach:

  1. a significant reduction in the primary endpoint of predefined morbidity within 75 days (11.8% versus 34.4%)
  2. reduced hospital stay (5.4 days vs 10.0 days; P < 0.001)
  3. reduced total hospital costs (€2919 vs €4262; P < 0.001)
  4. no difference in conversion to an open procedure between the approaches

Abstract:  Carsten. Acute Cholecystitis: Early Versus Delayed Cholecystectomy, A Multicenter Randomized Trial. Annals of Surgery 2013;258(3):385–393


Meta Analysis

Critical Care:     Cardiac Arrest Anti-Dysrhythmics

In a systematic review and meta analysis, totaling 10 randomized controlled and 7 observational studies, evaluating the effects of anti-arrhythmics during cardiopulmonary resuscitation:

  1. compared to placebo, amiodarone, lidocaine and nifekalant increased the rate of return of spontaneous circulation during initial resuscitation and survival to hospital admission
  2. amiodarone was superior to lidocaine (RR 1.28, 95% 0.57 - 2.86) and nifekalant (RR 0.50, 95% 0.19 - 1.31) for this initial resuscitation
  3. compared to placebo, amiodarone (RR 0.82, 95% 0.54 - 1.24), lidocaine (RR 2.26, 95% 0.93 - 5.52), magnesium (RR 0.82, 95% 0.54 - 1.24) and nifekalant did not improve survival to hospital discharge
  4. bretylium and sotalol were not beneficial

Full Text:  Huang. Anti-arrhythmia drugs for cardiac arrest: a systemic review and meta-analysis. Critical Care 2013;17:R173


Journal of Emergency Medicine:     Colloid Fluid Resuscitation

Using data from 17 randomized clinical trials (n=1281) to investigate the best colloid for fluid resuscitation in sepsis, Zhong et al determined there was no difference in mortality in studies comparing:

  1. albumin with hydroxyethyl starch (RR 0.98, 95% CI 0.74 - 1.30)
  2. albumin with gelatin (RR 2.4, 95% CI 0.31−18.35)
  3. gelatin versus hydroxyethyl starch (RR 1.02, 95% CI 0.79−1.32)
  4. hydroxyethyl starch with dextran (RR 1.38, 95% CI 0.28−6.78)

Abstract:  Zhong. Colloid Solutions for Fluid Resuscitation in Patients with Sepsis: Systematic Review of Randomized Controlled Trials. J Emer Med 2013;epublished August 9th


Emergency Medicine Journal:     Pulmonary Embolism

Pooling data from 12 studies including 13 cohorts (three retrospective, 10 prospective) (n=14 844) to evaluate the accuracy of pulmonary embolism rule-out criteria (PERC) in ruling out pulmonary embolism, Singh and colleagues demonstrated:

  1. sensitivity 0.97 (0.96 to 0.98)
  2. specificity 0.22 (0.22 to 0.23)
  3. positive liklihood ratio 1.22 (1.16 to 1.29)
  4. negative liklihood ratio 0.17 (0.13 to 0.23)
  5. diagnostic odds ratio 7.4 (5.5–9.8)

The authors concluded the combination of high sensitivity and low negative likelihood ratio allowed the PERC rule to be confidently applied in clinically low probability population settings.

Full Text:  Singh. Pulmonary embolism rule-out criteria (PERC) in pulmonary embolism—revisited: A systematic review and meta-analysis. Emerg Med J 2013;30:701-706


Critical Care & Resuscitation:     Non-Invasive Ventilation Post Extubation

Examining data from 14 studies (n=1211) to estimate the effects of non-invasive mechanical ventilation on the rate of reintubation among patients undergoing cardiothoracic surgery, Olper et al found:

  1. NIV reduced reintubation rates (RR 0.29; 95% CI 0.16 - 0.53; p < 0.0001; I2 = 0)
  2. NIV reduced hospital length of stay
  3. NIV reduced mortality
  4. Based on subgroup analysis, NIV was most beneficial in patients with ongoing acute respiratory failure (RR 0.25; 95% CI 0.07 - 0.89) and at high risk of developing postoperative pulmonary complications (RR 0.19; 95% CI 0.04 - 0.84)
  5. Prophylatic studies in low risk patients did not demonstrate a significant effect of NIV on reintubation rate (RR = 0.42; 95% CI 0.12 - 1.48)

Abstract:  Olper. Effects of non-invasive ventilation on reintubation rate: a systematic review and meta-analysis of randomised studies of patients undergoing cardiothoracic surgery. Crit Care Resusc 2013;15(3):220-7


Critical Care & Resuscitation:     Extracorporeal Membrane Oxygenation  

Zangrillo et al assessed data from 12 studies (n=1763) evaluating ECMO (mostly venoarterial) and reported:

  1. ECMO indications were varied but were usually respiratory failure, cardiogenic shock or both
  2. At 30 days, mortality was 54% (95% CI 47% - 61%), with 45% (95% CI  42% - 48%) of fatal events occurring during ECMO and 13% (95% CI 11% - 15%) after it
  3. The most common ECMO complications were: renal failure requiring continuous venovenous haemofiltration (occurring in 52%), bacterial pneumonia (33%), any bleeding (33%), oxygenator dysfunction requiring replacement (29%), sepsis (26%), haemolysis (18%), liver dysfunction (16%), leg ischaemia (10%), venous thrombosis (10%), central nervous system complications (8%), gastrointestinal bleeding (7%), aspiration pneumonia (5%), and disseminated intravascular coagulation (5%).

Abstract:   Zangrillo. A meta-analysis of complications and mortality of extracorporeal membrane oxygenation. Crit Care Resusc 2013;15(3):172-8


Observational Studies

Respiratory Care:     Oxygenation in Hypercapnoea

Savi and colleagues completed a prospective study evaluating the effects of 40 minute periods of administration of a high inspired oxygen concentration (FIO2=1) to 17 COPD patients during noninvasive ventilation and found:

  1. an increase in Pa02 (from  101.4 ± 21.7 mmHg to 290.5 ± 35.7 mmHg; p <0.001) (mean (±SD))
  2. no change in PaCO2 (from 52.6 ± 10.4 mmHg to 51.5 ± 12.3 mmHg)
  3. no change in respiratory rate (17.8 ± 3.7 breaths/min to 17.5 ± 2.8 breaths/min)
  4. no change in tidal volume (VT) (from 601 ± 8 mL to 608 ± 8 mL)
  5. no change in Glasgow coma scale (from 14.8 ± 0.3 to 14.8 ± 0.3 )

Full Text: Savi. Influence of inspired oxygen concentration on PaCO2 during noninvasive ventilation in patients with chronic obstructive pulmonary disease.Respir Care 2013;epublished August 13th

Journal of Anesthesia:     Coma Prognostication

To predict clinical outcome (dead or alive within 2 weeks), Miao and colleagues measured bispectral index (BIS), serum neuron-specific enolase (NSE) and S100 protein levels within the first 3 days of admission in 90 comatose patients with severe brain injuries and determined:

  1. BIS values were negatively correlated with serum NSE and S100 levels.
  2. the ability of the three measurements for the prediction of death (AUC) were:  BIS  0.841 (95 % CI  0.751–0.931, p < 0.001,), with an optimal cutoff of 32.5, NSE 0.713 (95 % CI  0.582–0.844, p = 0.002) and S100 0.790 (95 % CI  0.680–0.899, p < 0.001).
  3. patients with a BIS value >32.5 had significantly lower serum NSE and S100 protein levels, and a lower mortality, than patients with a BIS value ≤32.5.

Abstract:  Miao. Bispectral index predicts deaths within 2 weeks in coma patients, a better predictor than serum neuron-specific enolase or S100 protein. J Anesth 2013;epublished August 11th



Circulation:     Post-Cardiac Arrest PCI


Interventional Neurology:    Cerebral Vascular Disease



New England Journal of Medicine:     Speciality of Critical Care


New England Journal of Medicine:     Lung Transplant Allocation


Anaesthesia:     Post-Operative Nausea & Vomiting


Journal of Medical Society:     Plagiarism



Blood:     Thrombocytopaenia 


The Lancet Neurology:     Spinal Cord Injury


Anesthesiology News:     Death Definition


Review - Clinical


South Africian Journal of Anaesthesia & Analgesia:     Neurophysiological Monitoring


Asian Journal of Neurosurgery:     Subarachnoid Haemorrhage


Frontiers in Human Neuroscience:     Traumatic Brain Injury



Perioperative Medicine:     Crystalloid Fluid Therapy


Netherlands Heart Journal:     Heart-Lung Interactions


Frontiers in Physiology:     VO2 Max


Clinical Medicine Insights: Cardiology:     Dronedarone


Dimensions of Critical Care Nursing:     Genetic Cardiovascular Conditions


European Journal of Clinical Investigation:     Coronary Artery Assessment


European Journal of Clinical Investigation:     Myocardial Infarction Inflammation



Annals of Intensive Care:     Pharmacological Management of ARDS


Anesthesiology News:    Airway Ultrasound


Anesthesiology News:    Paediatric Supraglottic Airways




Thrombosis & Haemostasis:     Gastrointestinal Bleeding



Electrolytes and Blood Pressure:      Cardiorenal Syndrome


Thrombosis & Haemostasis:     Intrinsic Pathway Anticoagulation



Indian Journal of Allergy, Asthma and Immunology:     Allergen Immunotherapy 



Journal of Medical Society:     ICU Skin Conditions



Tuberculosis and Respiratory Diseases:     Critical Care Medicine Review 2013


Basic Science

Nature Communications

Abstract:  Lu. Repopulation of decellularized mouse heart with human induced pluripotent stem cell-derived cardiovascular progenitor cells. Nature Communications 2013;4:2307


Proceedings of the Natural Academy of Science:     Cerebral Activity at Cardiac Arrest

Abstract:  Borjigin. Surge of neurophysiological coherence and connectivity in the dying brain. Science 2013;epublished August 12th


Review - Non-Clinical

Journal of Experimental Neuroscience:     Teaching


European Journal of Education:     Open Educational Resources



I hope you find these brief summaries and links useful.

Until next week