March 24th 2013
Welcome to the 68th 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 has seen a plethora of interesting research studies published across NEJM, JAMA, AJRCCM and other journals. In addition to these high powered primary randomized controlled trials, there are secondary analyses from SAFE and EDEN. There are two reports from the Brussels meeting, including an update from the Italian ALBIOS study, partly presented at Lisbon last October.
This week's guidelines cover acute kidney injury, thallium poisoning and surgical antimicrobial prophylaxis.
Amongst the clinical review articles are two superb series from Critical Care. The first, "A selective look back and a glimpse forward" has just been featured as our topic of the week. The second, the "Annual Update in Intensive Care and Emergency Medicine 2013" features 10 reviews from this yearly update book which accompanies the Brussels meeting. As well as these series, there are neurological, respiratory, sepsis and circulatory review articles, including a great set of papers on embolic conditions from the International Journal of Critical Illness and Injury Science. There are also a couple of review articles on anaesthetic related topics - safety in anaesthesia and the postanaethetic unit.
The topic for This Week's Papers is the latest series from Critical Care, starting with a paper on recent advances in assessing volume responsiveness in mechanically ventilated patients in tomorrow's Paper of the Day.
American Journal of Respiratory and Critical Care Medicine: Activated Protein C
Annane and colleagues performed a multi-centre placebo-controlled, double-blind, 2x2 factorial design trial in 411 patients with persistent septic shock. Patients were randomly assigned to activated protein C alone, hydrocortisone and fludrocortisone alone, their respective combinations or their respective placebos. The trial was suspended in October 2011, after the worldwide withdrawal of activated protein C following the PROWESS Shock study (APC: n=208 and placebo: n=203). There was no significant interaction between APC and low-dose steroids (P=0.47). There was no difference in 90 day mortality (APC: 47.6% versus placebo: 46.3%; P=0.79). Similarly, there was no difference in any secondary outcomes or serious adverse events. Conclusion: In adults with persistent severe septic shock, APC was neither efficacous nor harmful.
American Journal of Respiratory and Critical Care Medicine: Research Recruitment
Burns et al completed a prospective, observational study of all critically ill adults eligible to participate in research studies at 23 Canadian ICUs. 8.9% of eligible patients made decisions for themselves. In 453 eligibility events, consent was not required in 14 (3.1%), missed in 131 (28.9%), infeasible due to operational reasons in 129 (28.5%), obtained in 140 (30.9%) and declined in 39 (8.6%). Over half (57%) of all opportunities to recruit patients were missed or infeasible largely due to research team workload, limited availability, narrow time windows for inclusion, difficulties in contacting families, non-existent substitute decision makers (SDMs), physician refusals and protocols prohibiting co-enrollment. The rationale for providing consent differed between patients and SDMs. Greater research coordinator experience and site research volume were significant predictors of fewer declined consents. Conclusion: Recruitment for research is problematic, with approximately 60% of possible opportunities missed; especially considering less than 10% of approaches for consent are declined.
American Journal of Respiratory and Critical Care Medicine: Weaning
Burns and colleagues undertook a pilot randomized trial comparing automated weaning (n=49) with protocolized weaning (n=43) in critically ill adults who tolerated at least 30 minutes of pressure support and either failed or were not yet ready to undergo a spontaneous breathing trial. Both groups utilized pressure support and spontaneous breathing trials, used a common PEEP/FiO2 chart, sedation protocol and criteria for extubation, reintubation and noninvasive ventilation. Patients treated with automated weaning had significantly shorter median times to first successful breathing trial (1.0 vs. 4.0 d, p<0.0001), extubation (3.0 vs. 4.0 d, p=0.02), successful extubation (4.0 vs. 5.0 d, p=0.01) and underwent fewer tracheostomies and episodes of protracted ventilation. Conclusion: In a small pilot study, automated weaning was superior to protocolized weaning with regard to ventilation outcomes.
Annals of the American Thoracic Society: Noninvasive Ventilation
Walkey et al identified 11,659,668 cases of acute respiratory failure from the American Nationwide Inpatient Sample during years 2000 to 2009 and evaluated NIV utilization trends and failure rates.The proportion of patients with COPD who received NIV increased from 3.5% in 2000 to 12.3% in 2009 (250% increase), and the proportion of patients without COPD who received NIV increased from 1.2% in 2000 to 6.0% in 2009 (400% increase). The rate of increase in the use of NIV was significantly greater for patients without COPD (18.1% annual change) than for patients with COPD (14.3% annual change; P = 0.02). Patients without COPD were more likely to have failure of NIV requiring endotracheal intubation (adjusted odds ratio, 1.19; 95% CI 1.15–1.22; P < 0.0001). Patients in whom NIV failed had higher hospital mortality than patients receiving mechanical ventilation without a preceding trial of NIV (adjusted odds ratio, 1.14; 95% CI 1.11–1.17; P < 0.0001). Conclusion: NIV usage has increased at a similar rate for all causes of respiratory failure, but is more likely to fail in patients without COPD, with NIV failure being associated with increased mortality.
British Medical Journal: Feeding in ALI
Needham and colleagues completed a prospective longitudinal follow-up evaluation of the randomized EDEN trial, to evaluate, for up to six days, the effect of initial low energy permissive underfeeding (“trophic feeding”) versus full energy enteral feeding (“full feeding”) on physical function and secondary outcomes in 525 patients with acute lung injury. Survivors had substantial physical, psychological, and cognitive impairments, reduced quality of life, and impaired return to work. Initial trophic versus full feeding did not affect mean SF-36 physical function at 12 months (55 (SD 33) v 55 (31), P=0.54), survival to 12 months (65% v 63%, P=0.63), or nearly all of the secondary outcomes. Conclusion: In survivors of acute lung injury, there was no difference in physical function, survival, or multiple secondary outcomes at 6 and 12 month follow-up after initial trophic or full enteral feeding.
Journal of Neurotrauma: Thromboprophylaxis in Traumatic Brain Injury
Aimun completed a systematic review and meta analysis (5 retrospective studies, n=1624) to assess the safety and efficacy of pharmacological prophylaxis within 72 h of traumatic brain injury. Pharmacological prophylaxis was dichotomized to early (n=713) or late (n=911) at 72 h post-injury. There were less venothromboembolic events in the early group (43 versus 106; risk ratio 0.52; 95% CI: 0.37 - 0.73), without an increase in the relative risk of intracranial hemorrhage progression 0.64 (95% CI: 0.35 - 1.14). Conclusion: In a systematic review and meta analysis of 5 retrospective studies, early pharmacological prophylaxis reduced the risk of venothromboembolism without affecting progression of intracranial hemorrhage.
Journal of Neurotrauma: Albumin in Traumatic Brain Injury
Cooper and colleagues performed a secondary analysis of the SAFE study, investigating 321 patients with traumatic brain injury who underwent intracranial pressure monitoring. There was a significant linear increase in mean ICP (1.30±0.33 vs. −0.37±0.36, p=0.0006) and significantly more deaths (34.4% vs. 17.4%; p=0.006) in the albumin group (n=164) compared with saline (n=157) when ICP monitoring was discontinued during the first week; but not when monitoring ceased during the second week (−0.08±0.44 vs. −0.23±0.38, p=0.79; and 18.6% vs. 12.1%; p=0.36 respectively). There were statistically significant differences in the mean total daily doses of morphine (−0.42±0.07 vs. −0.66±0.0, p=0.0009), propofol (−0.45±0.11 vs. −0.76±0.11; p=0.034) and noradrenaline (−0.50±0.07 vs. −0.74±0.07) and in temperature (0.03±0.03 vs. 0.16±0.03; p=0.0014) between the albumin and saline groups when ICP monitoring ceased during the first week. Conclusion: The most likely cause of increased mortality associated with albumin use in traumatic brain injury is an increase in intracranial pressure.
Surgical Infections: Tracheostomy
Park et al undertook an 8 year prospective single-institution study in 640 ICU patients to compare the incidence of surgical site infection (SSI) after open versus percutaneous tracheostomy and to discern whether there were any differences in outcome.The majority of patients were male (56.1%) and white (62.5%) with a mean age of 43.2±20.2 years, ISS of 30.7±13.2 points, and APACHE score of 13.3±6.3 points. The majority of patients were admitted for blunt trauma (85.1%). A total of 330 open and 310 percutaneous tracheostomies were performed, with 36 SSIs (5.3%) occuring. There was a lower rate of SSIs with percutaneous tracheostomy (3.4% versus 7%; p=0.04). There was no difference in hospital or ICU lengths of stay, or duration of mechanical ventilation. Conclusion: The risk of SSI is significantly lower after percutaneous than open tracheostomy.
New England Journal of Medicine: Cortisol Metabolism
Boonen and colleagues completed an observation study in 158 critically ill patients and 64 matched controls, testing five aspects of cortisol metabolism: (1) daily levels of corticotropin and cortisol; (2) plasma cortisol clearance, metabolism, and production during infusion of deuterium-labeled steroid hormones as tracers; (3) plasma clearance of 100 mg of hydrocortisone; (4) levels of urinary cortisol metabolites; and (5) levels of messenger RNA and protein in liver and adipose tissue, to assess major cortisol-metabolizing enzymes. Total and free circulating cortisol levels were consistently higher in the patients than in controls, whereas corticotropin levels were lower (P<0.001 for both comparisons). Cortisol production was 83% higher in the patients (P=0.02). There was a reduction of more than 50% in cortisol clearance during tracer infusion and after the administration of 100 mg of hydrocortisone in the patients (P≤0.03 for both comparisons). All these factors accounted for an increase by a factor of 3.5 in plasma cortisol levels in the patients, as compared with controls (P<0.001). Impaired cortisol clearance also correlated with a lower cortisol response to corticotropin stimulation. Reduced cortisol metabolism was associated with reduced inactivation of cortisol in the liver and kidney, as suggested by urinary steroid ratios, tracer kinetics, and assessment of liver-biopsy samples (P≤0.004 for all comparisons). Conclusion: During critical illness, reduced cortisol breakdown, related to suppressed expression and activity of cortisol-metabolizing enzymes, contributed to hypercortisolemia and hence corticotropin suppression.
- Editorial: Gomez-Sanchez. Adrenal Dysfunction in Critically Ill Patients. N Eng J Med 2013; epublished March 19th
Journal of the American Medical Association: Severe Sepsis
Opal and colleagues performed a randomized, double-blind, placebo-controlled, multinational phase 3 trial investigating whether eritoran, a TLR4 antagonist which blocks lipopolysaccharide-TLR4 binding, would significantly reduce sepsis-induced mortality. Patients with severe sepsis (n = 1961) were randomized and treated within 12 hours of onset of first organ dysfunction in a 2:1 ratio with a 6-day course of either eritoran tetrasodium (105 mg total) or placebo. Baseline characteristics of the 2 study groups were similar. In the modified intent-to-treat analysis (randomized patients who received at least 1 dose) there was no significant difference in the primary end point of 28-day all-cause mortality with 28.1% (366/1304) in the eritoran group vs 26.9% (177/657) in the placebo group (P = 0.59; hazard ratio 1.05; 95% CI 0.88-1.26; difference in mortality rate, −1.1; 95% CI −5.3 to 3.1) or in the key secondary end point of 1-year all-cause mortality with 44.1% (290/657) in the eritoran group vs 43.3% (565/1304) in the placebo group, Kaplan-Meier analysis of time to death by 1 year, P = 0.79 (hazard ratio 0.98; 0.85-1.13). No significant differences were observed in any of the prespecified subgroups. Adverse events, including secondary infection rates, did not differ between study groups. Conclusion: Among patients with severe sepsis, eritoran did not result in reduced 28-day mortality.
Journal of the American Medical Association: Heart Failure
Gheorghiade et al completed an international, double-blind, placebo-controlled study investigating whether aliskiren (150 mg, increased to 300 mg as tolerated), a direct renin inhibitor, when added to standard therapy, would reduce the rate of cardiovascular death or heart failure rehospitalization among hospitalized heart failure patients. 1639 patients were randomized, with 1615 patients included in the final efficacy analysis cohort (808 aliskiren, 807 placebo). Mean age was 65 years; mean LVEF, 28%; 41% of patients had diabetes mellitus, mean estimated glomerular filtration rate, 67 mL/min/1.73 m2. At admission and randomization, median NT-proBNP levels were 4239 pg/mL and 2718 pg/mL, respectively. In total, 24.9% of patients receiving aliskiren (77 cardiovascular deaths, 153 heart failure rehospitalizations) and 26.5% of patients receiving placebo (85 cardiovascular deaths, 166 heart failure rehospitalizations) experienced the primary end point at 6 months (hazard ratio 0.92; 95% CI 0.76-1.12; P = 0.41). At 12 months, the event rates were 35.0% for the aliskiren group (126 cardiovascular deaths, 212 heart failure rehospitalizations) and 37.3% for the placebo group (137 cardiovascular deaths, 224 heart failure rehospitalizations; HR 0.93; 95% CI 0.79-1.09; P = 0.36). The rates of hyperkalemia, hypotension, and renal impairment/renal failure were higher in the aliskiren group compared with placebo. Conclusion: Among patients hospitalized for HF with reduced LVEF, initiation of aliskiren in addition to standard therapy did not reduce CV death or HF rehospitalization at 6 months or 12 months after discharge.
Abstract: Gheorghiade. Effect of Aliskiren on Postdischarge Mortality and Heart Failure Readmissions Among Patients Hospitalized for Heart Failure: The ASTRONAUT Randomized Trial. JAMA 2013;309(11):1125
Serlipressin in Septic Shock
Vincent et al presented a phase 1 trial of Serlipressin (selective V1 agonist) in septic shock. There is some animal data suggesting serlipressin may reduce vascular permeability & leak, reducing fluid requirements. Ten patients were treated with low dose serlipressin, and 19 at higher dose (2.5 ng/kg/min). Serlipressin therapy was associated with decreased noradrenaline requirements, increased shock resolution at 48 hours, increased ventilator-free days at 7 days, and less positive fluid balance (6.5 vs 9L) at 7 days. A phase II trial is now planned.
Albumin in Severe Sepsis and Septic Shock (ALBIOS Study)
- Early (randomised within 6 hours) - no difference (mortality 40.6% in both groups)
- Late (6-24 hours) - 41.3 vs 45% in favour of albumin (not significant)
- Septic shock 90-day mortality 42.6% vs 48.4% (P=0.03)
- Also benefit in subgroups with higher no of organ failures.
many thanks to JS for forwarding these results
Journal of the Royal College of Physicians of Edinburgh: Acute Kidney Injury
- Feehally. RCPE UK Consensus Conference Statement: Management of acute kidney injury: the role of fluids, e-alerts and biomarkers. J R Coll Physicians Edinb 2013;43(1):37-8
Clinical Journal of the American Society of Nephrology: Thallium Poisoning
Surgical Infections: Antimicrobial Prophylaxis in Surgery
Review - Clinical
Frontiers in Neurology: Traumatic Brain Injury
- Woodcock. The role of markers of inflammation in traumatic brain injury. Front Neurol 2013; epublished March 4th
Frontiers in Neurology: Functional MRI
- Graner. Functional MRI in the investigation of blast-related traumatic brain injury. Front Neurol 2013; epublished March 4th
International Journal of Critical Illness and Injury Science: Embolic Disease
- Thongrong. Amniotic fluid embolism. Int J Crit Illn Inj Sci 2013;3:51-7
- Stawicki. Septic embolism in the intensive care unit. Int J Crit Illn Inj Sci 2013;3:58-63
- Kwiatt. Fat embolism syndrome. Int J Crit Illn Inj Sci 2013;3:64-8
- Tarbox. Pulmonary embolism. Int J Crit Illn Inj Sci 2013;3:69-72
- Gordy. Vascular air embolism. Int J Crit Illn Inj Sci 2013;3:73-6
- Lyaker. Arterial embolism. Int J Crit Illn Inj Sci 2013;3:77-87
Clinical Cardiology: Cardiac Valve Disease
Electrolytes and Blood Pressure: Cardio-Renal Syndrome
InTech: Cardiac Output Monitoring
- Critchley. Minimally Invasive Cardiac Output Monitoring in the Year 2012. Book Chapter in "Artery Bypass"; Aronow (Ed.), ISBN: 978-953-51-1025-5, InTech 2013
InTech: Biomarkers of Cardiac Ischaemia
- Gaze. Biomarkers of Cardiac Ischemia.Book Chapter in "Ischemic Heart Disease". Gaze (Ed.), ISBN: 978-953-51-0993-8, InTech 2013.
Respirology: Pulmonary Mesenchymal Stem Cells
Surgical Infections: Silver as an Antimicrobial
- Politano. Use of Silver in the Prevention and Treatment of Infections: Silver Review. Surgical Infections 2013;14(1):8-20
Perioperative Medicine: Postanaesthetic Care Unit
Swiss Medical Weekly: Anaesthetic Safety
- Haller. Improving patient safety in medicine: is the model of anaesthesia care enough? Swiss Med Wkly 2013;143:w13770
Review - Basic Science
The Open Biochemistry Journal: Nitric Oxide
- Mian. Nitric Oxide and its Metabolites in the Critical Phase of Illness: Rapid Biomarkers in the Making. The Open Biochemistry Journal 2013;7:24-32
Critical Care Series
Critical Care: Annual Update in Intensive Care and Emergency Medicine 2013
- Schneider. Measurement of kidney perfusion in critically ill Patients. Critical Care 2013;17:220
- Ricksten. Renal oxygenation in clinical acute kidney injury. Critical Care 2013;17:221
- Cortes. Two steps forward in bedside monitoring of lung mechanics: transpulmonary pressure and lung volume. Critical Care 2013;17:219
- Meybohm. Point-of-care coagulation management in intensive care medicine. Critical Care 2013;17:218
- Monnet. Assessment of volume responsiveness during mechanical ventilation: recent advances. Critical Care 2013;17:217
- Schmid. Patient monitoring alarms in the ICU and in the operating room. Critical Care 2013;17:216
- Sandroni. Therapeutic hypothermia: is it effective for non-VF/VT cardiac arrest? Critical Care 2013;17:215
- Giraud. Cardiac index during therapeutic hypothermia: which target value is optimal? Critical Care 2013;17:214
- Guarracino. Ventriculo-arterial decoupling in acutely altered hemodynamic states. Critical Care 2013;17:213
- Lipp. Analgesia in the emergency department: a GRADE-based evaluation of research evidence and recommendations for practice. Critical Care 2013;17:212
Critical Care: A selective look back and a glimpse forward
- Marini. Mechanical ventilation: past lessons and the near future. Critical Care 2013, 17(Suppl 1):S1
- Vincent. Critical care - where have we been and where are we going? Critical Care 2013, 17(Suppl 1):S2
- Singer. Advancing critical care: time to kiss the right frog. Critical Care 2013, 17(Suppl 1):S3
- Gattinoni. Supporting hemodynamics: what should we target? What treatments should we use? Critical Care 2013, 17(Suppl 1):S4
- Donati. Towards integrative physiological monitoring of the critically ill: from cardiovascular to microcirculatory and cellular function monitoring at the bedside. Critical Care 2013, 17(Suppl 1):S5
- Bartels. Rational fluid management in today's ICU practice. Critical Care 2013, 17(Suppl 1):S6
- Wischmeyer. The evolution of nutrition in critical care: how much, how soon? Critical Care 2013;17(Suppl 1):S7
- Westphal. Get to the point in intensive care medicine - the sooner the better? Critical Care 2013;17(Suppl 1):S8
- Marini. Our favorite unproven ideas for future critical care. Critical Care 2013;17(Suppl 1):S9
I hope you find these brief summaries and links useful.
Until next week