April 21st 2013
Welcome to the 72nd 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 has been a busy week for critical care research publications, with the headline study being the long awaited REDOXS trial, which unfortunately reports increased mortality with glutamine use, and no effect from anti-oxidants in the critically ill. Also, there are positive studies on selenium, linezolid, subglottic stenosis and copper surfaces for the prevention of hospital acquired infections and colonizations. Balancing this are negative studies, demonstrating a lack of efficacy of sodium bicarbonate for the prevention of post-operative acute kidney injury, and an interesting physiological study showing no increase in renal blood flow with a fluid bolus. The era of organogenesis slow approaches, with a report in Nature Medicine of a successfully engineered rat kidney.
There are a number of guidelines published this week, with the standout article being an updated version of the European haemorrhage guideline. Similarly, there are several commentaries, including discussions on mechanical ventilation, high frequency oscillation, H7N9 influenza and carbapenam resistant bacteria.
Amongst the clinical review articles are papers on septic encephalopathy, levosimendan, Takosubo cardiomyopathy, inhalation injury, rapid sequence induction, tissue engineering for small intestine and liver, protein requirements in the critically ill, thromboelastography, and a critical care update paper.
New England Journal of Medicine: Pharmaconutrition
Heyland and colleagues performed a blinded 2-by-2 factorial trial in 1223 critically ill adults with multiorgan failure and receiving mechanical ventilation, to receive supplements of glutamine, antioxidants (selenium, zinc, beta carotene, vitamin E, and vitamin C), both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. Glutamine therapy was associated with a trend toward increased mortality at 28 days (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% CI 1.00 - 1.64; p=0.05) and with increased in-hospital (37.2% versus 31.0, p=0.02) and 6 month mortality (43.7% versus 37.2%, p=0.02). Antioxidants had no effect on 28-day mortality (anti-oxidants 30.8%, versus no anti-oxidants 28.8%; adjusted odds ratio, 1.09; 95% CI 0.86 - 1.40; p=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).
PLoS Medicine: Bicarbonate for Kidney Injury Prevention
Haase et al performed a multicenter, double-blind, randomized controlled trial in 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass, comparing 24 hours of intravenous infusion of sodium bicarbonate (n=174, 5.1 mmol/kg) or sodium chloride (n=176, 5.1 mmol/kg) on the incidence of post-operative acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL), initiation of acute renal replacement therapy, and mortality. The study was stopped early due to a likely lack of efficacy and possible harm. At baseline, a greater proportion of patients in the sodium bicarbonate group presented with preoperative chronic kidney disease compared to control (38% versus 25%; p = 0.009). Sodium bicarbonate therapy was associated with a higher incidence of AKI (47.7% versus 36.4%, odds ratio 1.60, 95% CI 1.04–2.45; unadjusted p = 0.032). After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90–2.33], p = 0.120]). A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p = 0.011). The incidence of postoperative renal replacement therapy was similar but hospital mortality was increased in patients receiving sodium bicarbonate compared with control (6.3% versus 1.7%, OR 3.89 [1.07–14.2], p = 0.031).
Full Text: Haase. Prophylactic Perioperative Sodium Bicarbonate to Prevent Acute Kidney Injury Following Open Heart Surgery: A Multicenter Double-Blinded Randomized Controlled Trial. PLoS Med 2013;10(4):e1001426
Intensive Care Medicine: Hypothermia for Cardiac Arrest
Vaahersalo completed a prospective observational study evaluating all 548 adult out-of-hospital cardiac arrest (OHCA) patients admitted to 21 ICUs in Finland from March over a one year period. 311 patients (56.8%) had a shockable initial rhythm (incidence of 7.4/100,000/year) and 237 patients (43.2%) had a non-shockable rhythm (incidence of 5.6/100,000/year). At ICU admission, 504 (92%) patients were unconscious. Therapeutic hypothermia was given to 241/281 (85.8 %) unconscious patients resuscitated from shockable rhythms, with unfavourable 1-year neurological outcome (cerebral performance categories, CPC 3–4–5) in 42.0% with therapeutic hypothermia versus 77.5 % without therapeutic hypothermia (p < 0.001). Therapeutic hypothermia was given to 70/223 (31.4 %) unconscious patients resuscitated from non-shockable rhythms, with 1-year CPC of 3–4–5 in 80.6% (54/70) with therapeutic hypothermia versus 84.0 % (126/153) without therapeutic hypothermia (p = 0.56). This lack of difference remained after adjustment for propensity to receive therapeutic hypothermia in patients with non-shockable rhythms.
Critical Care: ECMO
Aubron and colleagues completed an analysis of a 5 year prospective ECMO database consisting of 158 ECMO therapies in 151 patients. Two thirds were treated with veno-arterial ECMO and one-third with veno-venous ECMO. VV ECMO was associated with a significantly shorter duration of ECMO (median/IQR: 7/5-10 versus 10/6-16) with over 70% of ECMO cases successfully weaned in each group. The overall mortality was 37.3% (VA ECMO 37.1% and VV ECMO 37.7%). Haemorrhagic events, assessed by the total of red blood cells units received during ECMO were associated with hospital mortality for both ECMO types.
Intensive Care Medicine: ECMO
In 10 mechanically ventilated ARDS patients receiving femoro–jugular vv-ECMO blood gases and hemodynamic parameters were evaluated after changing one of three ECMO settings: circuit blood flow, FiO2ECMO (fraction of inspired oxygen in circuit), or sweep gas flow ventilating the membrane, while leaving the other two parameters at their maximum setting. Bood flow was the main determinant of arterial oxygenation, while CO2 elimination depended on sweep gas flow through the oxygenator. An ECMO flow/cardiac output >60 % was constantly associated with adequate blood oxygenation and oxygen transport and delivery.
Critical Care: Enoxaparin Dosing
Robinson et al completed a double-blind randomized controlled trial in 80 critically ill patients weighing 50 - 90 kilograms, comparing different regimes of subcutaneous (sc) enoxaparin: 40 mg once daily (QD), 30 mg twice daily (BID), 40mg BID, or 1mg/kg QD, each administered for three days. On day 1, mean peak anti-Xa levels were similar with 40 mg QD (n= 20, 0.20 IU/ml) and 40 mg BID (n=19, 0.17 IU/ml), lower with 30 mg BID (n= 20, 0.08 IU/ml) and higher with 1 mg/kg QD (n=19, 0.34 IU/ml). At steady state (day 3), mean peak anti-Xa levels were: 40 mg QD (0.13 IU/ml), 30 mg BID (0.15 IU/ml), 40 mg BID (0.33 IU/ml) and 1 mg/kg QD (0.40 IU/ml), with these difference being statistically significant (p <0.0001). Doses of 40 mg BID and 1mg/kg QD enoxaparin yielded target anti-Xa levels for over 80% of the study period. There were no adverse effects.
Nature Medicine: Renal Organogenesis
Song et al performed a proof-of-concept study, engineering a kidney and successfully transplanting into a rat. Rat, porcine and human kidneys were decellularized by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. These scaffolds were seeded with rat epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo.
British Journal of Anaesthesia: Perioperative Anaphylaxis
Gibbs and colleagues analysed the 2000–2009 database of the West Australian Anaesthetic Mortality Committee for perioperative anaphylaxis events. From approximately 3 million anaesthetics there were 264 cases, giving a perioperative anaphylaxis rate of ∼1:11 000. There were no anaphylaxis-related deaths (95% CI: 0–1.4%).
Intensive Care Medicine: Sedation
Shehabi et al conducted a multicentre prospective longitudinal cohort study in 259 patients sedated and mechanically ventilated ≥24 h. Midazolam was the main sedative prescribed. Adjusted multivariable Cox proportional hazard regression analysis showed that early deep sedation was independently associated with longer time to extubation (hazard ratio 0.93, 95% CI 0.89–0.97, p=0.003), increased hospital mortality (HR 1.11, 95 % CI 1.05–1.18, P < 0.001) and increased 180-day mortality (HR 1.09, 95 % CI 1.04–1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44 %) of patients.
Full Text: Shehabi. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study (SPICE study). Intensive Care Med 2013;39(5):910-918
Critical Care Medicine: Outcomes post ICU
In a cohort study of 91,203 Dutch ICU survivors discharged alive from hospital, the mortality risk at 1, 2, and 3 years was 12.5%, 19.3%, and 27.5%, respectively. The 3-year mortality after hospital discharge in ICU patients was higher than the weighted average of the gender and age-specific death risks of the general Dutch population (27.5% versus 8.2%). In comparison with general ICU patients, elective and cardiac surgical patients had lower adjusted hazard ratios for mortality (0.73 and 0.28, respectively), while medical and cancer patients had higher adjusted hazard ratios for mortality (1.41, 1.94, respectively).
Critical Care Medicine: ECMO in Cardiac Arrest
Maekawa et al perfomed a post hoc analysis of a Japanese prospective observational database to compare neurologic outcome following extracorporeal cardiopulmonary resuscitation (n=53) with conventional cardiopulmonary resuscitation (n=109) in adults with witnessed cardiac arrest of cardiac origin who had undergone cardiopulmonary resuscitation for longer than 20 minutes. Propensity score matching was used to reduce selection bias and balance the baseline characteristics and clinical variables that could potentially affect outcome (n=24 both groups). Intact survival rate was higher in the matched extracorporeal cardiopulmonary resuscitation group than in the matched conventional cardiopulmonary resuscitation group (29.2% [7/24] vs. 8.3% [2/24], log-rank p = 0.018). According to the predictor analysis, only pupil diameter on hospital arrival was associated with neurologic outcome (adjusted hazard ratio, 1.39 per 1-mm increase; 95%CI 1.09–1.78; p = 0.008).
Abstract: Maekawa. Extracorporeal Cardiopulmonary Resuscitation for Patients With Out-of-Hospital Cardiac Arrest of Cardiac Origin: A Propensity-Matched Study and Predictor Analysis. Crit Care Med 2013;41(5):1186-1196
Critical Care Medicine: Effects of Fluid Challenge on Renal Perfusion
Schnell and colleagues performed a prospective cohort study in 35 patients in 3 French ICUs to assess renal resistive index variations in response to fluid challenge. 17 (49%) were fluid responsive (had at least a 10% increase in aortic blood flow). After fluid challenge, mean arterial pressure increased from 73 mm Hg (IQR 68–79) to 80 mm Hg (75–86; p < 0.0001) and stroke volume from 50 mL (30–77) to 55 mL (39–84; p < 0.0001). Stroke volume changes after fluid challenge were +28.6% (+18.8% to +38.8%) in fluid challenge responders and +3.1% (–1.6% to 7.4%) in fluid challenge nonresponders. Renal resistive index was unchanged after fluid challenge in both nonresponders (0.72 [0.67–0.75] before and 0.71 [0.67–0.75] after fluid challenge; p = 0.62) and responders (0.70 [0.65–0.75] before and 0.72 [0.68–0.74] after fluid challenge; p = 0.11). Stroke volume showed no correlations with resistive index changes after fluid challenge in the overall population (r2 = 0.04, p = 0.25), in fluid challenge responders (r2 = –0.02, p = 0.61), or in fluid challenge nonresponders (r2 = 0.08, p = 0.27). Stroke volume did not correlate with resistive index changes after fluid challenge in the subgroups without acute kidney injury, with transient acute kidney injury, or with persistent acute kidney injury.
Critical Care Medicine: Selenium
Alhazzani and colleagues performed a systematic review and meta analysis to determine the efficacy and safety of high-dose selenium supplementation compared to placebo for the reduction of mortality in patients with sepsis. Nine trials (n=792) were included. Selenium supplementation in comparison to placebo was associated with lower mortality (odds ratio, 0.73; 95% CI, 0.54, 0.98; p = 0.03; I2 = 0%). Among patients receiving and not receiving selenium, there was no difference in ICU length of stay (mean difference, 2.03; 95% CI, -0.51, 4.56; p = 0.12; I2 = 0%) or nosocomial pneumonia (odds ratio, 0.83; 95% CI, 0.28, 2.49; p = 0.74; I2 = 56%).
Abstract: Alhazzani. The Effect of Selenium Therapy on Mortality in Patients With Sepsis Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Crit Care Med 2013; epublished April 12th
Australian Critical Care: Subglottic Suctioning
In a systematic review and meta analysis, consisting of 9 randomized trials, subglottic drainage was estimated to reduced the risk of ventilator-associated pneumonia (fixed-effect relative risk0.52, 95% CI, 0.42–0.65), but not of ICU mortality (RR 1.05 (95% CI, 0.86–1.28) or for hospital mortality was 0.96 (95% CI, 0.81–1.12). Subglottic drainage was associated with a reduced duration of mechanical ventilation was −1.04 days (95% CI, −2.79–0.71).
International Journal of Antimicrobial Agents: MRSA Therapy
An and colleagues undertook a meta analysis (9 RCTs, n=5249) to compare the efficacy and safety of linezolid with vancomycin for meticillin-resistant Staphylococcus aureus (MRSA)-related infections. Linezolid was associated with superior efficacy compared with vancomycin for MRSA-related infection in terms of clinical treatment success [8 RCTs, 2174 patients, odds ratio =1.77, 95% CI 1.22–2.56] and microbiological treatment success (9 RCTs, 1555 patients, OR=1.78, 95% CI 1.22–2.58). Although no difference was found regarding the overall incidence of drug-related adverse events and serious AEs between the linezolid and vancomycin therapy groups (drug-related AEs, 8 RCTs, 5034 patients, OR=1.20, 95% CI 0.98–1.48; SAEs, 5 RCTs, 2072 patients, OR=1.00, 95% CI 0.74–1.36), the linezolid therapy group was associated with significantly fewer patients experiencing abnormal renal function (4 RCTs, 2531 patients, OR=0.39, 95% CI 0.28–0.55).
Abstract: An. Linezolid versus vancomycin for meticillin-resistant Staphylococcus aureus infection: a meta-analysis of randomised controlled trials. International Journal of Antimicrobial Agents 2013;41(5):426-433
Infection Control and Hospital Epidemiology: ICU-Acquired Infections
Salgado and colleagues undertook a randomized control trial in 614 patients placed randomly in available rooms with or without copper alloy surfaces, to determine the effect of copper surfaces on rates of hospital-acquired infections and/or colonization with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant Enterococcus (VRE). HAIs and MRSA or VRE colonization rates were significantly lower in patients treated in rooms with copper surfaces than standard rooms (0.071 versus 0.123, p=0.020). For HAI only, the rate was reduced from 0.081 to 0.034 (p=0.013).
Mayo Clinic Proceedings: L-Carnitine in Acute Myocardial Infarction
DiNicolantonio and colleagues completed a systematic review and meta-analysis (13 controlled trials, n=3629) to evaluate the effects of L-carnitine in the setting of acute myocardial infarction.
This intervention was associated with reductions in all-cause mortality (odds ratio 0.73; 95% CI 0.54-0.99; p=0.05; risk ratio 0.78; 95% CI 0.60-1.00; p=.005), incidence of ventricular arrthymias (RR 0.35; 95% CI 0.21-0.58; P<.0001), and development of angina (RR 0.60; 95% CI 0.50-0.72; p<.00001), with no reduction in the development of heart failure (RR 0.85; 95% CI 0.67-1.09; p=0.21) or myocardial reinfarction (RR 0.78; 95% CI 0.41-1.48; p=0.45).
Critical Care: European Haemorrhage Guideline
- Spahn. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Critical Care 2013;17:R76
Journal of the American College of Cardiology: Type B Aortic Dissection
- Fattori. Interdisciplinary Expert Consensus Document on Management of Type B Aortic Dissection. J Am Coll Cardiol 2013;61(16):1661
Nephrology: Initiating Renal Replacement Therapy at End of Life
- Crail. Renal Supportive and Palliative Care: Position Statement. Nephrology 2013;epublished April 15th
Annals of Internal Medicine: Social Medicine
- Farnan. Medical Professionalism: Patient and Public Relationships: Policy Statement From the American College of Physicians and the Federation of State Medical Boards. Ann Intern Med 2013;Epublished April 11th
New England Journal of Medicine: Mechanical Ventilation
- Klompas. Complications of Mechanical Ventilation — The CDC's New Surveillance Paradigm. N Engl J Med 2013;368:1472-1475
Journal of the American Medican Association: Bacterial Resistance
- Notes from the Field: Hospital Outbreak of Carbapenem-Resistant Klebsiella pneumoniae Producing New Delhi Metallo-Beta-Lactamase—Denver, Colorado, 2012. JAMA 2013;309(15):1582
- Kuehn. “Nightmare” Bacteria on the Rise in US Hospitals, Long-term Care Facilities. JAMA 2013;309(15):1573
Journal of the American Medican Association: Leading Causes of Death in the USA 2010
Nature: H7N9 Influenza
- Butler. H7N9 bird flu poised to spread.Cases reported in new regions of China. Nature 2013; epublished April 15th
Critical Care: High-Frequency Oscillation
- Goligher. Re-evaluating high-frequency oscillation for ARDS: Would a targeted approach be successful? Critical Care 2013;17:133
Review - Clinical
Brazilian Journal of Intensive Care: Septic Encephalopathy Biomarkers
- Zenaide. Biomarkers in septic encephalopathy: a systematic review of clinical studies. Rev Bras Ter Intensiva 2013;25(1):56-62
Journal of Clinical Pharmacology: Levosimendan
- Pathak. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther 2013 April 18th
Clinical and Experimental Pharmacology and Physiology: Ticagrelor
- Steiner. Ticagrelor: positive, negative and misunderstood properties as a new antiplatelet agent. Clin Exp Pharmacol Physiol 2013; epublished April 16th
Clinical Pharmacology: Advances and Applications: Ticagrelor
- Davis. Advances in antiplatelet technologies to improve cardiovascular disease morbidity and mortality: a review of ticagrelor. Clinical Pharmacology: Advances and Applications 2013;5(1):67-83
Swiss Medical Weekly: Cardiac Arrest
- Hunziker. Importance of leadership in cardiac arrest situations: from simulation to real life and back. Swiss Med Wkly 2013;143:w13774
Vascular Health and Risk Management: Takosubo Cardiomyopathy
- Redfors. Stress-induced cardiomyopathy (Takotsubo) – broken heart and mind? Vascular Health and Risk Management 2013;9:149–154
Annals of Cardiothoracic Surgery: Type A Aortic Dissection
- Iturra. Should the dissected aortic arch be replaced in acute type A dissection? The Mayo Clinic perspective. Ann Cardiothorac Surg 2013;2(2):202-204
- Appoo. Strategies in the surgical treatment of type A aortic arch dissection. Ann Cardiothorac Surg 2013;2(2):205-211
- Grabenwoger. Type A aortic dissection: the extent of surgical intervention. Ann Cardiothorac Surg 2013;2(2):212-215
- Roselli. We should replace the aortic arch and more in DeBakey type I dissection - A perspective from the Cleveland Clinic. Ann Cardiothorac Surg 2013;2(2):216-221
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine: Inhalational Injury
- Dries. Inhalation injury: epidemiology, pathology, treatment strategies. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2013;21:31
Columbian Journal of Anaesthesiology: Rapid Sequence Intubation
- Jaramillo. Rapid sequence intubation in the intensive care unit. Rev Colomb Anestesiol 2013;41(1):24–33
Current Opinion in Anesthesiology: Thoracic Ultrasound
- Piette. Basic concepts in the use of thoracic and lung ultrasound. Curr Opin Anesthesiol 2013;26:20–30
Respiratory Research: Pulmonary Fibrosis
- Kaarteenaho. The current position of surgical lung biopsy in the diagnosis of idiopathic pulmonary fibrosis. Respiratory Research 2013;14:43
Respirology: Lung Stem Cells
Clinical Gastroenterology and Hepatology: Small Bowel Tissue Engineering
- Spurrier. Tissue Engineering the Small Intestine. Clinical Gastroenterology and Hepatology 2013;11(4):354-358
Brazilian Journal of Intensive Care: Protein Requirements in the Critically Ill
- da Cunha. Protein requirements, morbidity and mortality in critically ill patients: fundamentals and applications. Rev Bras Ter Intensiva 2013;25(1):49-55
Liver International: Liver Tissue Engineering
- Palakkan. Liver tissue engineering and cell sources: issues and challenges. Liver Int 2013;33:666–676
Clinical and Experimental Pharmacology and Physiology: Renal Oxygenation
- Evans. Haemodynamic influences on kidney oxygenation: Clinical implications of integrative physiology. Clinical and Experimental Pharmacology and Physiology 2013;40:106–122
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine: Thromboelastography
- da Luz. Thrombelastography (TEG(R)): practical considerations on its clinical use in trauma resuscitation. Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine 2013;21:29
Current Opinion in Anesthesiology: Coagulation Management in Cardiac Surgery
- Weber. Perioperative coagulation management during cardiac surgery. Curr Opin Anesthesiol 2013;26(1):60-64
Columbian Journal of Anaesthesiology: Perioperative Paediatric Bleeding
- Giraldo. Pediatric perioperative bleeding – Basic considerations. Rev Colomb Anestesiol 2013;41(1):44–49
- Giraldo. Management of perioperative bleeding in children. Step by step review. Rev Colomb Anestesiol 2013;41(1):50-56
ISRN Cardiology: Troponin Measurement in Sepsis
- Hussain. Elevated Cardiac Troponins in Setting of Systemic Inflammatory Response Syndrome, Sepsis, and Septic Shock. ISRN Cardiology 2013;2013:723435
Journal of Infectious Diseases: Malaria
Journal of Emergency Trauma and Shock: Sternal Fracture
Journal of Emergency Trauma and Shock: Combined Tracheoesophageal Trauma
- Hamid. Combined tracheoesophageal transection after blunt neck trauma. J Emerg Trauma Shock 2013;6:117-22
Journal of Thoracic Diseases: Critical Care Update
Critical Care Nurse: Dogmatic Practice
- Makic. Putting Evidence Into Nursing Practice: Four Traditional Practices Not Supported by the Evidence. Crit Care Nurse 2013;33:28-42
Journal of Pharmacology and Pharmacotherapeutics: Drug Reactions in the Elderly
Review - Non-Clinical
BMC Biology: Open Access Publications
- O Brown. An interview with Patrick O Brown on the origins and future of open access. BMC Biology 2013;11:33
Journal of Pharmacology and Pharmacotherapeutics: Writing and Publishing
- Saxena. Scientific evaluation of the scholarly publications. J Pharmacol Pharmacother 2013;4:125-9
- Balakumar. The critical steps for successful research: The research proposal and scientific writing. J Pharmacol Pharmacother 2013;4:130-8
Journal of Pharmacology and Pharmacotherapeutics: Computer-Assisted Undergraduate Learning
- John. A review of computer assisted learning in medical undergraduates. J Pharmacol Pharmacother 2013;4:86-90
I hope you find these brief summaries and links useful.
Until next week