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Critical Care Reviews Newsletter

July 21^st 2013

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Welcome to the 85th 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 randomized research studies include an interesting Greek trial reporting improved outcomes in cardiac arrest with a cocktail of vasopressin and steroids, reductions in traumatic brain associated intracranial hypetension with half-molar sodium lactate, a lack of superiority of 1:1:1 transfusion ratios in trauma in addition to increased plasma wastage, reduced cerebral vasospasm with lumbar CSF drainage post aneurysm clipping in subarachnoid haemorrhage plus improved sedation with early goal-directed sedation compared with standard sedation. A mete analysis reports a possible effect of blood purification on sepsis outcomes and observational studies report the effects of prone positioning on mechanicl ventilation, the association of diaphragmatic dysfunction on outcome, reduced mortality in mechanically ventilated patients over the past 15 years and the complication rate of intra-hospital transfers.

There is a simple position statement from the European Society of Cardiology on the management of myocarditis and a critique on the Early TIPS study.

Amongst the clinical review articles are papers on thiopentone cerebroprotection, cerebral vasospasm, fluid optimization, pulmonary hypertension, estimating renal function in the critically ill, melatonin, antifungal therapy, and inflammation in burns. My favourite paper regards the possibility of head transplantation - a therapeutic option to ponder for your next impossible case. The latest set of articles recently made freely available from the major journals are also included.

The topic for This Week's Papers is blood components, starting with a paper on red cell concentrates in tomorrow's Paper of the Day.

Research

Randomized Controlled Trial

Journal of the American Medical Association: Cardiac Arrest

Mentzelopoulos and colleagues completed a randomized, double-blind, placebo-controlled, parallel-group trial in 268 consecutive patients with cardiac arrest and compared a regimen of adrenaline (1mg/CPR cycle of approximately 3 minutes), plus vasopressin (20 IU/CPR cycle for the first 5 cycles) plus methylprednisolone (40 mg in the first cycle only) {VSE group, n=130) with adrenaline (1mg/CPR cycle) plus saline placebo {control group, n=138). In survivors, post resuscitation shock was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73). VSE therapy was associated with both a higher probability for return of spontaneous circulation of 20 minutes or longer (primary outcome) (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio 2.98; 95% CI 1.39-6.40; P = 0.005) and survival to hospital discharge with cerebral performance category score of 1 or 2 (18/130 [13.9%] vs 7/138 [5.1%]; OR 3.28; 95% CI 1.17-9.20; P = 0.02). Post resuscitation patients with shock and treated with VSE had higher probability for survival to hospital discharge with cerebral performance category scores of 1 or 2 (16/76 [21.1%] vs 6/73 [8.2%]; OR 3.74; 95% CI 1.20-11.62; P = 0.02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. There was no difference in adverse events.

Abstract: Mentzelopoulos. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2013;310(3):270

Intensive Care Medicine: Intracranial Hypertension

Ichai completed a double-blind, randomized controlled trial comparing the efficiency of half-molar sodium lactate (SL) versus saline serum solutions in preventing episodes of raised intracranial pressure (ICP) in 60 patients with severe traumatic brain injury. Within the 48-h study period, half molar sodium lactate therapy was associated with less episodes of intracranial hypertension (23 versus 53 episodes, p < 0.05). Similarly, less patients treated with half-molar sodium lactate had episodes of intracranial hypertension {11 (36 %) versus 20 patients (66 %), p < 0.05}. Cumulative 48-h fluid and chloride balances were reduced in the sodium lactate group compared to the control group (both p < 0.01).

Abstract: Ichai. Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial. Intensive Care Med 2013;39(8):1413-1422

Stroke: Minocycline

In a multi-center prospective randomized open-label blinded pilot study comparing minocycline 100 mg IV (n=47), commenced within 24 hours of onset of stroke and continued 12 hourly for a total of 5 doses, with no minocycline (n=48), the intervention was not associated with improved survival free of handicap (29/47 (65.9%) versus 33/48 (70.2%); rate ratio 0.94; 95% CI 0.71–1.25; odds ratio 0.73; 95% CI 0.31–1.71). In a meta-analysis of 3 heterogenous human trials, minocycline was associated with an increased odds of handicap-free survival (odds ratio 2.99; 95% CI 1.74–5.16).

Abstract: Kohler. Intravenous Minocycline in Acute Stroke: A Randomized, Controlled Pilot Study and Meta-Analysis. Stroke 2013;epublished July 18th

Canadian Medical Association Journal: Trauma Transfusion

Nascemento et al undertook a single centre randomized controlled trial to compare a fixed-ratio (1:1:1) transfusion protocol (n = 40) with a laboratory-results-guided transfusion protocol (control; n = 38) in bleeding, hypotensive patients expected to undergo massive transfusion. The primary outcome was the success in achieving a 1:1:1 transfusion ratio, with secondary safety outcomes being mortality and ARDS. A transfusion ratio of 1:1:1 was achieved in 57% (21/37) of patients in the fixed-ratio group and 6% (2/32) in the control group, with a greater plasma wastage seen with the intervention protocol (22% [86/390] of FP units v. 10% [30/289] in the control group). A ratio of 1:1 (RBC:FP) was achieved in 73% (27/37) in the fixed-ratio group and 22% (7/32) in the control group. There was no difference in the 28-day mortality or number of days free of acute respiratory distress syndrome.

Full Text: Nascimento. Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results-guided transfusion in patientswith severe trauma: a randomized feasibility trial. CMAJ 2013;epublished July 15th

Neurosurgery: Subarachnoid Haemorrhage

In a randomized controlled trial in 60 subarachnoid haemorrhage patients having undergone cerebral artery aneurysm clipping, lumbar cerebrospinal fluid drainage (n=30) was associated with reduced vasospasm (30% versus 63%; p=0.01) and a lesser incidence of vasospasm related cerebral infarction (20% versus 53%; p = 0.007). There was no difference in mean duration of hospital stay, although lumbar drainage was associated with a higher Glasgow Outcome Score at 1 and 3-months.

Abstract: Borkar. Spinal cerebrospinal fluid drainage for prevention of vasospasm in aneurysmal subarachnoid haemorrhage: a prospective randomized controlled study. Neurosurgery 2013 Aug;60 Suppl 1:180-1

Critical Care Medicine: Sedation

Shehabi and colleagues perfromed a pilot prospective, multicenter, randomized, controlled trial to assess the feasibility and safety of early goal-directed sedation (n=21) compared with standard sedation (n=16). Early goal-directed sedation was associated with more patients being lightly sedated on days 1 (63.2% vs 14.3%), 2 (90.5% vs 53.3%) and 3 (90.5% vs 60%), more richmond agitation sedation scale assessments between –2 and 1 at 48 hours (203/307 [66%] versus (74/197 [38%]; p = 0.01), more delirium free days (101/175 (58%) versus 54/114 (47%); p = 0.27) and less requirement for physical restraints (1 (5%) versus 5 (31%); p = 0.03).

Abstract: Shehabi. Early Goal-Directed Sedation Versus Standard Sedation in Mechanically Ventilated Critically Ill Patients: A Pilot Study (SPICE study). Critical Care Medicine 2013;41(8):1983-1991

Stroke: Stroke Craniotomy

In a 3 year follow up in the HAMLET study, comparing surgical decompression (n=32) for space occupying cerebral infarction with best medical therapy (n=32), standard therapy, results at 1 year were sustained at 3 years, with surgery having no effect on risk of poor functional outcome (absolute risk reduction 1%; 95% CI −21 to 22), but reducing case fatality (absolute risk reduction 37%; 95% CI 14–60). Sixteen surgically treated patients and 8 controls lived at home (absolute risk reduction 27%; 95% CI 4–50%).

Abstract: Geurts. Surgical Decompression for Space-Occupying Cerebral Infarction: Outcomes at 3 Years in the Randomized HAMLET Trial. Stroke 2013;epublished July 18th

Lancet Neurology: Stroke Thrombolysis

In an 18 month followup of the IST-3 cohort, an open-label, international, multicentre, randomised, controlled trial in 3035 patients evaluating the effect of alteplase thrombolysis within 6 hours of ischaemic stroke, there was no difference in mortality (alteplase 408/1169 (34.9%) versus control 414/1179 (35.1%), p=0.85), but an improvement in disability (Oxford handicap scale of 0-2, 35% versus 31.4%; adjusted odds ratio 1·28, 95% CI 1·03—1·57; p=0·024). Alteplase therapy wasalso associated with a favourable shift in the distribution of OHS grades (adjusted common OR 1·30, 95% CI 1·10—1·55; p=0·002) and a high higher self-reported health (adjusted mean difference in EuroQoL utility index 0·060; p=0·019).

Abstract: The IST-3 collaborative group. Effect of thrombolysis with alteplase within 6 h of acute ischaemic stroke on long-term outcomes (the third International Stroke Trial [IST-3]): 18-month follow-up of a randomised controlled trial. Lancet Neurology 2013;12(8):768-776

Interventional Non-Randomized Controlled Trial

Journal of the American College of Cardiology: Pulmonary Arterial Hypertension

Chen and colleagues performed a pilot non-randomized controlled study, evaluating the effect of pulmonary artery denervation in patients with pulmonary arterial hypertension resistant to medical therapy. The intervention (n=13), in comparison with medical therapy (n=8), was associated with a reduction of mean pulmonary artery pressure (from 55±5 mmHg to 36±5 mmHg, p<0.01), echocardiographic improvement, with tricuspid excursion increase (from 0.3±0.04 to 0.50±0.04, p<0.001) and functional improvement in 6 minute walk test (from 324±21 m to 491±38 m, p<0.006).Abstract: Chen. Pulmonary artery denervation to treat pulmonary arterial hypertension: a single-center, prospective, first-in-man PADN-1 study. JACC 2013;epublished July 10th

Systematic Review & Meta Analysis

Critical Care Medicine: Blood Purification

Zhou et al performed a systematic review and meta analysis of randomized trials (16 trials, n = 827) to determine the association between various blood purification techniques, including hemofiltration, hemoperfusion and plasma exchange, in comparison with hemodialysis with no blood purification, on all-cause mortality in sepsis. Blood purfication was associated with decreased mortality (35.7% vs 50.1%; risk ratio 0.69, 95% CI 0.56-0.84; p < 0.001). This result was largely driven by Japanese trials of polymyxin B hemoperfusion, with removal of these trials resulting in loss of this survival effect (risk ratio 0.89, 95% CI 0.71-1.13; p = 0.36; eight trials, n = 457).

Abstract: Zhou. Blood Purification and Mortality in Sepsis: A Meta-analysis of Randomized Trials. Crit Care Med 2013;epublished July 15th

Observational Studies

American Journal of Respiratory and Critical Care Medicine: Prone Positoning

Using whole-lung computed tomography during breath-holding sessions at airway pressures of 5, 15, and 45-cmH₂O, Cornejo et al completed an observational study investigating the protective effects of prone positioning in 24 patients with ARDS. In the supine position, increasing PEEP from 5 to 15 cm H₂0 decreased non-aerated tissue (501±201 to 322±132grs, p<0.001) and increased tidal-hyperinflation (0.41±0.26 to 0.57±0.30%, p=0.004). Prone positioning further decreased non-aerated tissue (322±132 to 290±141grs, p=0.028), and reduced tidal-hyperinflation observed at PEEP 15 in supine (0.57±0.30 to 0.41±0.22%). Cyclic recruitment/derecruitment only decreased when high PEEP and prone were applied together (4.1±1.9 to 2.9±0.9%, p=0.003), particularly in patients with high lung recruitability.

Abstract: Cornejo. Effects of Prone Positioning on Lung Protection in Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2013;epublished July 10

American Journal of Respiratory and Critical Care Medicine: Diaphragmatic Dysfunction

Demoule et al completed a dual centre prospective, observational cohort study investigating the incidence, risk factors, and prognostic impact of diaphragmatic impairment in 85 consecutive patients at ICU admission and 2 days later, with diaphragmatic function assessed by twitch tracheal pressure in response to bilateral anterior magnetic phrenic nerve stimulation (Ptr,stim).On Day 1, Ptr,stim was 8.2 (5.9–12.3) cm H₂O and 64% of patients had Ptr,stim less than 11 cm H₂O. Independent predictors of low Ptr,stim were sepsis and Simplified Acute Physiology Score II. Compared with nonsurvivors, both ICU survivors (9.7 [6.3–13.8] vs. 7.3 [5.5–9.7] cm H₂O; P = 0.004) and hospital survivors (9.7 [6.3–13.5] vs. 7.8 [5.5–10.1] cm H₂O; P = 0.004) had higher Ptr,stim versus nonsurvivors. Day 1 and Day 3 Ptr,stim were similar.

Abstract: Demoule. Diaphragm Dysfunction on Admission to the Intensive Care Unit. Prevalence, Risk Factors, and Prognostic Impact—A Prospective Study. Am J Respir Crit Care Med 2013;188(2):213-219

JAMA Surgery: Trauma Transfusion

Kutcher and colleagues undertook a single centre prospective observational study in 174 trauma patients receiving a massive transfusion (>10 units of RBCs in 24 hours) or requiring the activation of the massive transfusion protocol, to evaluate whether reduced crystalloid and higher red cell to plasma transfusion ratios are associated with improved outcomes. Over the 7 year study period, both crystalloid and blood product administration reduced in the first 24 hours (P < 0.05). The red cell to plasma ratio non-significantly decreased (1.84:1 in 2007 to 1.55:1 in 2011, P = 0.20). When adjusted for age and injury characteristics using Cox regression, each decrease of 0.1 achieved in the massive transfusion protocol’s red cell to plasma ratio was associated with a 5.6% reduction in mortality (P = 0.005). Despite these changes, injury severity and mortality remained unchanged.

Abstract: Kutcher. A Paradigm Shift in Trauma Resuscitation: Evaluation of Evolving Massive Transfusion Practices. JAMA Surg 2013;epublished July 17th

American Journal of Respiratory and Critical Care Medicine: Mechanical Ventilation

As the characteristics of mechanically ventilated patients, plus their management, has changed over time, Esteban and colleagues sought to determine whether mortality in mechanically ventilated patients has changed over time by comparing data from prospective cohort studies conducted in 1998, 2004, and 2010, including 18,302 patients from 927 units in 40 countries. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in PEEP (mean 4.2 cm H₂O [SD = 3.8] in 1998 to 7.0 cm of H₂O [SD = 3.0] in 2010). Comparing 1998 with 2010, both crude ICU mortality (28 versus 31%; odds ratio 0.87; 95% CI 0.80–0.94), and hospital mortality decreased, despite a similar complication rate. After adjusting for baseline and management variables, this difference remained significant (odds ratio 0.78; 95% CI 0.67–0.92).

Abstract: Esteban. Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation. Am J Respir Crit Care Med 2013;188(2):220-230

Critical Care Medicine: Obesity

In an observational cohort study including 154,308 patients from the Dutch National Intensive Care Evaluation registry, Pickkers et al demonstrated body mass index to be associated with hospital mortality. Patients with the lowest BMI ( < 18.5 kg/m²) had the greatest mortality, while obese and seriously obese patients (30–39.9 kg/m²) had the lowest risk of death, with an adjusted odds ratio of 0.86 (0.83–0.90).

Abstract: Pickkers. Body Mass Index Is Associated With Hospital Mortality in Critically Ill Patients: An Observational Cohort Study. Crit Care Medicine 2013;41(8):1878-1883

Critical Care Medicine: Intrahospital Transport

Schwebel et al performed a prospective observational multicenter cohort study, evaluating intrahospital transport complications in 3,006 transfers from 1,782 critically ill mechanically ventilated patients. Using propesity analysis, matching 1,659 intrahospital transport patients to 3,344 nonintrahospital transport patients, intrahospital transport was associated with a higher complication risk (odds ratio 1.9; 95% CI 1.7–2.2; p < 10^–4), including pneumothorax, atelectasis, ventilator-associated pneumonia, hypoglycemia, hyperglycemia, and hypernatremia. Intrahospital transport was associated with a longer ICU length of stay (mean 12 days [IQR 6–23] vs 5 [3–11] d, p < 10^–4), but had no effect on mortality.

Abstract: Schwebel. Safety of Intrahospital Transport in Ventilated Critically Ill Patients: A Multicenter Cohort Study (OUTCOMEREA Study). Crit Care Med 2013;41(8):1919-1928

Critical Care Medicine: Acute Lung Injury

In a single centre prospective, observational study in 256 patients with bilateral opacities on a chest radiograph, and without isolated left atrial hypertension, Levitt and colleagues showed oxygen requirement, maximal respiratory rate, and baseline immune suppression were independent predictors of progression to acute lung injury, and that a simple three-component early acute lung injury score (1 point for oxygen requirement > 2–6 L/min or 2 points for > 6 L/min; 1 point each for a respiratory rate ≥ 30 and immune suppression) accurately identified patients who progressed to acute lung injury requiring positive pressure ventilation (AUC 0.86). An early acute lung injury score ≥ 2 identified patients who progressed to acute lung injury with 89% sensitivity and 75% specificity. 25% of he cohort progressed to ALI requiring positive pressure ventilation in a median time of 20 hours.

Abstract: Levitt. Early Acute Lung Injury: Criteria for Identifying Lung Injury Prior to the Need for Positive Pressure Ventilation. Crit Care Med 2013;41(8):1929-1937