If you just want the final verdict on all our reviews, you have come to the right place. Here is the catalogue of all our 'Bottom Line' conclusions. The links will direct you to the full summary and critique of the papers and access to the manuscripts (abstract or full text), commentaries and further learning resources.

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The implementation of an early rehabilitation program is associated with reduced length of stay: A multi-ICU study
Wahab. Journal of the Intensive Care Society. 2016, Vol. 17(1) 2–11
Early rehabilitation for patients on ICU makes logical sense and this retrospective study supports the implementation of a critical care rehabilitation programme. However, with less than half a day reduction in ICU stay (which might also be attributed to other factors), it would be difficult to justify such a large scale recruitment of therapists. The descriptive statistics are however informative and perhaps it can be used to compare against our own therapy provision. Future RCT studies looking at longer term outcome measures (physical, psychological and patient experience) would be helpful, particularly in formulating larger scale programmes and cost analysis through QUALY data
BLISS: Beta-Lactam Infusion in Severe Sepsis: a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis
Abdul-Aziz. ICM 2016; doi:10.1007//s00134-015-4188-0
This study confirms that CI has a superior PK/PD profile compared to IB regiments. The higher clinical cure rate, ventilator free days and faster resolution of white cell count in the CI group did not translate to a mortality benefit at both 14 and 30 days. Given the weakness in this study and the simplicity of IB regiment, I will continue to use this in my daily practice
Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock
Ventura. Crit Care Med. 2015;43(11):2292-302
The single centre randomised controlled trial in Brazil, demonstrated an increased mortality when dopamine, compared with adrenaline, was used to treat paediatric patients with septic shock. Patients treated with dopamine had a longer time until they were fully resuscitated, they had a greater need for renal replacement therapy, and greater number of hospital acquired infections. Further multi-centre trials are urgently needed to confirm these findings.
APPAC: Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis
Salminen. JAMA 2015; 313:2340-2348. doi:10.1001/jama.2015.6154
There may be a subset of patients with uncomplicated appendicitis that can be safely treated by antibiotics and not surgery. This trial is based on a different treatment paradigm to the UK; here diagnostic laparoscopy is more common (as is ultrasound) and the risk of removing a normal appendix is accepted. Overall I would not use this paper alone to change practice in this country, but it could be useful in other countries, where the diagnostic process is different
Eurotherm3235 Trial: Hypothermia for Intracranial Hypertension after Traumatic Brain Injury
Andrews. NEJM Published first on line Oct 2015. DOI: 10.1056/NEJMoa1507581
In patients with elevated intracranial pressure after TBI, therapeutic hypothermia, in addition to standard treatment, results in a greater risk of death and worse neurological outcomes in survivors compared to standard measures
AVOID: Air Versus Oxygen in ST-Segment Elevation Myocardial Infarction
Stub. Circulation 2015; 131:2143-2150. DOI: 10.1161/circulationaha.114.014494
This trial fails to show any benefit in giving oxygen to normoxic patients with STEMI undergoing PCI and may in fact cause harm
The results should be interpreted cautiously as the endpoints are surrogate outcomes only. However, there is sound physiological evidence to suggest hyperoxia is harmful. We await results of An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction (DETO2X-AMI) which has clinical meaningful morbidity and mortality outcomes
Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial
Appleboam. The Lancet 2015; published online first 25th August 2015. DOI 10.1016/S0140-6736(15)61485-4
The modified Valsalva technique is a simple, effective, cost-free and well tolerated postural modification to the standard Valsalva technique. This study supports the use of the modified Valsalva technique, over the standard approach, as an early treatment for haemodynamically stable patients presenting with a supraventricular tachycardia
Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial
Motov. 2015;Annals of Emergency Medicine;66(3)222-229
In patients with acute moderate to severe pain, the use of subdissociative ketamine achieved a similar reduction in pain scores compared with morphine. It resulted in an increased number of minor side effects post-injection, that had resolved by 30 minutes. Further evidence will be required for me to change from my current standard of morphine.
BLING2: A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis
Dulhunty. Am J Respir Crit Care Med. First published online 22 Jul 2015. DOI: 10.1164/rccm.201505-0857OC
In ICU patients, with underlying pathophysiological changes of sepsis and organ dysfunction, there appears to be no benefit from continuous infusion of beta-lactam antibiotics compared to intermittent bolus infusion. Given the simplicity of an intermittent bolus infusion, this should be the preferred method for these antibiotics in this patient group
HEAT Trial: Acetaminophen for Fever in Critically Ill Patients with Suspected Infection
Young P. NEJM 2015; published on line first 5th October 2015. DOI: 10.1056/NEJMoa1508375

Early administration of paracetamol to ICU patients to treat fever due to probable infection results in a moderate reduction in temperature but does not effect mortality at 28 or 90 days. The observation that it may result in a longer ICU stay in nonsurvivors and shorter ICU stay in survivors should be interpreted cautiously and only as hypothesis generating.
Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomised clinical trial
Young P. JAMA. Published online October 07, 2015. doi:10.1001/jama.2015.12334
There was no difference in the incidence of acute kidney injury in patients receiving Plasma-Lyte 148 compared to 0.9% saline. Whilst more data from the trial is awaited, I will continue to use balanced solutions.
The study does provide reassurance that in elective or moderately sick intensive care patients, giving up to 2L 0.9% sodium chloride results in no increased risk of kidney injury compared with Plasma-Lyte 148
FELLOW trial: Randomized Trial of Apneic Oxygenation during Endotracheal Intubation of the Critically Ill
Semler. Am J Respire Care Med; published online first 1st October 2015.
In this medical ICU, where patients were being intubated by experienced fellows, and where the operator did not think that video laryngoscopy was essential, apneic oxygenation did not increase lowest arterial oxygen saturation compared to usual care. No harm was demonstrated
Litigation associated with intensive care unit treatment in England: an analysis of NHSLA data 1995–2012
In 17 years, £20 million has been spent on claims relating to ICU care in NHS hospitals in England. The most common claims related to pressure sores followed by infection, including the acquisition of MRSA. The clinical category with the highest number of claims related to patient death was respiratory/airway followed by missed/delayed diagnosis. Intensive care units should review their practice to ensure that they have guidelines, staffing and environments that minimise the risks identified. This study highlights the importance of good quality note keeping to enable staff to write statements on events that occurred ≥four years previously
Intravascular Complications of Central Venous Catherization by Insertion Site
JJ Parient et al. on behalf of 3SITES Study Group. 2015; NEJM 373:1220-1229
This study confirmed conventional wisdom that the use of subclavian veins for CVC catheterisation was associated with low risk of infection but highest risk of pneumothoraces. However, in this study, the use of ultrasound for subclavian CVC was relatively low.
This study has not changed my practice and I will continue using ultrasound guided internal jugular lines as my first choice technique. I would choose the femoral route over subclavian. If a subclavian line is needed, I would continue using ultrasound to guide insertion accepting that the risk might be higher
EPO-TBI: Erythropoietin in traumatic brain injury: a double-blind randomised controlled trial
Nichol A. The Lancet 2015; Online Oct 6 2015
This trial does not support the use of Erythropoietin for patients with moderate or severe TBI. It does alert the neurointensivist to the high incidence of proximal DVT in this patient group, although the clinical significance of this is not explored in this trial
Heyland: Recovery after critical illness in patients aged 80 years or older
Heyland. Intensive Care Medicine 2015; 41:1911-1920. doi:10.1007/s00134-015-4028-2

Patients over 80 years old admitted to ICU for more than 24 hours have a poor recovery profile: 25% return to baseline after a year, 25% are alive but significantly worse than baseline and 50% are dead. These data appear reliable and generalisable to most developed healthcare systems, and this might help guide communication and decision making with patients, families and referring clinicians
ROC-CCC: Trial of Continuous or Interrupted Chest Compressions during CPR
Nichol. NEJM 2015; published online first (accessed 19th November 2015). doi:10.1056/NEJMoa1509139
This complex trial attempted to test a subtle modification to the early phase of resuscitation care in out-of-hospital cardiac arrests and did not demonstrate any convincing benefit from continuous chest compressions over conventional interrupted chest compressions
THAPCA-OH: Therapeutic hypothermia after out-of-hospital cardiac arrest in children
Moler. NEJM 2015; 372:1898-1908. doi:10.1056/NEJMoa1411480
Therapeutic hypothermia after out-of-hospital cardiac arrest in children cannot be recommended based on the results of this trial. Although this trial demonstrated no difference between normothermia and hypothermia, a false negative conclusion is possible and the confidence intervals are wide. The longer survival over time observed with hypothermia may indicate that children treated with therapeutic hypothermia are at similar risk of death but it is delayed due to alterations in the pathophysiology
BRIDGE Study: Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation
Douketis and the BRIDGE Investigators. NEJM 2015. Published on line first 22nd June 2015. doi:10.1056/NEJMoa1501035
In patients with chronic (permanent or paroxysmal) atrial fibrillation or atrial flutter, stopping warfarin peri-operatively for a short duration does not result in an increased risk of thromboembolism and reduces the incidence of minor bleeding. Patients with mechanical heart valves were excluded from this study
Therapeutic Hypothermia in Deceased Organ Donors and Kidney-Graft Function
Niemann NEJM;2015;,373(5)405-14; DOI: 10.1056/NEJMoa1501969
In organ donors, following death by neurological criteria, the use of therapeutic hypothermia vs. normothermia, significantly decreased the recipient's requirement for dialysis during the 1st week post-transplant. This benefit was more marked for patients at a higher risk of graft failure. Further studies are required to confirm this finding, to demonstrate the longterm outcomes, and to investigate the outcomes for other organs that are transplanted.
PermiT: Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults
Arabi. NEJM 2015; 372:2398-2408. doi:10.1056/NEJMoa1502826
This study confirms an association between weekend day admissions and increased mortality within 30-days. However, in-patients are less likely to die on a weekend day than on a week day. The many confounding variables limit the conclusions that can be drawn and it should be considered hypothesis generating only. It is likely that differences in baseline characteristics between patients who are admitted at the weekend vs. weekday, account for at least part of the mortality difference found. There is no evidence presented in this study to firmly support the hypothesis that increasing senior presence and elective weekend work will reduce mortality.
Paracetamol therapy and outcome of critically ill patients: a multicenter retrospective observational study
Suzuki et al. Critical Care 2015; 19:162: 1-11 doi: 10.1186/s-015-0865-1
In critically ill patients, paracetamol was associated with a decreased mortality. There are many potential confounding variables that may account for this. A RCT is required to determine any outcome benefit. I eagerly await the results of the HEAT trial
STOP-IT: Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection
Sawyers et al. N Engl J Med 2015: 372:1996-2005
An important study addressing antibiotic stewardship. In the UK, antibiotic courses are usually 5 - 7 days when adequate source control has been achieved. This study demonstrates that it might be reasonable to reduce this course even further in patients with low severity illness scores. Certainly in this underpowered study, prolonged courses of antibiotic therapy do not seem to have any additional benefit in this patient group
Age of Transfused Blood in Critically Ill Adults
Lacroix et al. Canadian Critical Care Trials Group. NEJM 2015; 372:1410-1418. doi:10.1056/NEJMoa1500704
This study shows that fresh blood which has been stored for < 8 days is no better than blood stored up to 42 days. Transfusion triggers and processes for safe administration of blood are probably more important
A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters
Loubani. Journal of Critical Care 2015; 30(3):654
This narrative review provides no firm conclusion. From the distribution of events described, it is reasonable to conclude that the use proximal venous catheters for not more than 6 hours in emergencies, whilst a central venous catheter is inserted, is acceptable. This work should form a base for subsequent trials if the question remains clinically relevant
FLORALI: High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure
Frat. NEJM 2015; first published on line on May 17th 2015
This study demonstrates that high-flow oxygen via nasal cannula is non-inferior to oxygen delivered by a non-rebreather facemask and BiPAP in reducing the subsequent need for intubation.
High flow oxygen reduces ICU and 90 day mortality compared with the other strategies. It also subjectively improves dyspnoea and respiratory discomfort at one hour compared with the other oxygen delivery devices. Further studies are required to confirm whether high flow oxygen is beneficial in pulmonary and extra pulmonary causes of hypoxaemia and to determine its efficacy in ARDS
PREOXYFLOW: High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomised controlled clinical trial
Vourc'h M. Intensive Care Medicine 2015; published online first April 2015
In this study, using high-flow nasal cannula, without discontinuation during an apnoeic period, was not any more effective than using a high FiO2 facemask at 15 l/min for preventing desaturation during RSI. Given the methodological and statistical concerns, this cannot be concluded with certainty, and if the question is still of interest then a larger RCT is needed.
STOPAH: Prednisolone or Pentoxifylline for Alcoholic Hepatitis
Thursz. NEJM 2015; 372:1619-28
This study was under-powered to demonstrate clinically relevant effects. However, it suggests strongly with a low risk of bias that pentoxifylline 400mg daily for 28 days has no beneficial effect whilst prednisolone 40mg daily for 28 days may be beneficial for short-term outcomes but not for medium or long-term outcomes. From these data (with wide confidence intervals that cross the null hypothesis line) Prednisolone NNT (28-day mortality) is 23; Prednisolone NNH (serious adverse infection) is 16
Gu: Single-Dose Etomidate Does Not Increase Mortality in Patients with Sepsis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Studies
Chest 2015;147(2):335-346
This meta-analysis did not find evidence of harm from single-dose etomidate, but the trials on which it is based are small and the comparators are not clearly defined. Therefore, whilst there are alternative agents for cardio-stable induction, this trial does not provide evidence to support etomidate use over and above these other agents. Of note, the conclusion in this paper contradicts other recent meta-analyses
Lilja: Cognitive Function in Survivors of Out-of-Hospital Cardiac Arrest After Target Temperature Management at 33ºC Versus 36ºC
Lilja et al. Circulation.2015, Published online February 13
In patients that have basic life support quickly initiated following an OOH cardiac arrest the use of targeted temperature management of 33°C vs. 36°C does not affect cognitive function at six months
Significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia
Lyon. Critical Care 2015; 19:134
In this service evaluation, an association between induction with fentanyl + ketamine + rocuronium and a favourable clinical course was shown. Methodological weaknesses limit the strength of what can be concluded from this. The study design prevents conclusions of causation from being drawn
TITRe2: Liberal or Restrictive Transfusion after Cardiac Surgery
Murphy. NEJM 2015;372(11):997-1008. doi:10.1056/NEJMoa1403612
In a group of patients with cardiovascular disease that have recently undergone cardiac surgery, a transfusion threshold of 75 g/l demonstrated no benefit over a transfusion threshold of 90 g/l. There is possibly a trend towards increased morbidity, and an (unexplained) statistically significant increase in mortality from a 75 g/l transfusion threshold. Global interpretation of this study is "in this group of patients, a transfusion threshold of 90 g/l is most appropriate", but this RCT does not conclusively show this in my opinion. It does suggest that clinicians are justified in tailoring transfusion thresholds of between 75 and 90 g/l to individual patients, as there is no definite harm and no cost difference (in the UK) from these two limits
Torres: Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients with Severe Community-Acquired Pneumonia and High Inflammatory Response
Torres et al. JAMA 2015; 313(7):677-687. doi:10.1001/jama.2015.88
This study raises an interesting question, and the methodology to answer this is reasonable. However, the small numbers and composite, surrogate primary outcome limit the generalisability. The authors are conducting a larger trial to investigate this further. Clinical practice should not be changed based upon this trial alone
Monitor trial: Protocolized fluid therapy in brain-dead donors: the multicenter randomized
A Ali-Khafaji et al. ICM 2015 Online First January 1-9
The use of protocolised fluid therapy resulted in the use of more fluids in the intervention arm but no difference in the use of vasoactive drugs. The lack of benefit may be a result of a number of reasons including being under-powered and protocol violation. I will continue to adhere to local guidelines develop in collaboration with regional transplant teams
PROPPR: Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma. JAMA. 2015;313(5):471-482
JAMA. 2015;313(5):471-482
Among patients with severe trauma and major bleeding there was no significant difference in 24 hour or 30 day mortality in patients who received a blood product transfusion at a ratio of 1:1:1 compared to a ratio of 1:1:2. However the study was significantly underpowered for the observed difference in mortality found. A ratio of 1:1:1 resulted in reduced mortality from exsanguination within the 1st 24 hours, with similar complication rates to a lower ratio protocol. Therefore, I will continue to aim for a 1:1:1 ratio in this population
ProMISe: Trial of Early, Goal-Directed Resuscitation for Septic Shock
ProMISe Trial Investigators. 2015; published on line published on March 17 DOI: 10.1056/NEJMoa1500896
ProMISe does not demonstrate any difference in 90-day survival between usual care and strict EGDT in hospitals in England. Importantly, this study also demonstrates that EGDT is not cost effective. This is a landmark paper and completes the international triumvarate of sepsis studies. ProMISE, ARISE and ProCESS have shown no benefit (or harm) with EGDT over 'usual care', unlike the Rivers study. Both groups in this study were actually well matched for most interventions. The main difference was in the use of continuous SCVO2 measurement and CVP to guide management. Perhaps we should not completely dismiss the term 'EGDT'. Afterall, our 'usual care' consists of early intervention and goal directed therapy. The goal... to continue to reduce mortality with high standard and consistent quality care.
CHEER: Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion. Resuscitation January 2015. Volume 86, Pages 88–94
Stub D, et al. Resuscitation January 2015. Volume 86, Pages 88–94 (first published on line Oct 2014) doi:10.1016/j.resuscitation.2014.09.010
The CHEER protocol has been shown to improve survival with favourable neurological outcome following cardiac arrest compared with historical data. It works and works very well in this experienced ECMO centre, with engagement of pre-hospital services and as part of a bundle. A multi-centre RCT is now required to determine if these impressive results can be replicated.
PYTHON: Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis
Bekker. N Engl J Med 2014; 371:1983-93
Allowing patients with severe pancreatitis three to four days to initiate oral intake appears to be safe and effective. This can reduce the discomfort, cost and complications associated with tube feeding in these patients. Although well-conducted this was a relatively small trial, and future data may change this picture
DESTINY II: Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke
DESTINY II Investigators. NEJM 2014;370:1091-1100
In older patients with malignant MCA infarction an early decompressive hemicraniectomy significantly improves mortality but leaves the vast majority of survivors with moderately severe or severe disability. This therefore leaves us with the difficult question of whether this treatment should be offered or performed
CALORIES: Trial of the Route of Early Nutritional Support in Critically Ill Adults
NEJM 2014; 371:1673-1684
Early nutritional support through the parenteral route is neither more harmful nor more beneficial than through the enteral route. Enteral feeding does increase episodes of vomiting and hypoglycaemia but with no evidence of harm or nosocomial infection. Daily calorific targets were rarely achieved in this study (< 40% in both groups). This reflects a possible deficiency in our feeding protocols and adherence within UK and highlights the need for this to be addressed
VITdAL-ICU: Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients with Vitamin D Deficiency
Amrein. JAMA 2014; 312:1520-30. doi:10.1001/jama.2014.13204
This well designed trial suggests that severe vitamin D deficiency in critically ill patients may benefit from high-dose supplementation, but as a single-centre and relatively small trial the findings need to be validated by further trials before a treatment recommendation can be made
Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation 2014;(85),1337-1341
Driver. Resuscitation 2014;(85),1337-1341
The use of esmolol for refractory VF was associated with a dramatic, but non significant, improvement in mortality. This association may be due to a causal effect of esmolol. However, the small sample size or confounding variables such as the use of therapeutic hypothermia and emergent cardiac catheterisation may also account for the differences found. Further studies are required. In the mean time, if I have a patient with refractory VF, with no other treatment options available such as cardiac catheterisation I will use esmolol prior to stopping resuscitation. Survival with good neurological outcome can be achieved with prolonged CPR (56-68 minutes)
Weingart: Delayed Sequence Intubation: A Prospective Observational Study
Weingart. Annals of Emergency Medicine 2014
In a prospective observational study of patients requiring emergency intubation who did not tolerate pre-oxygenation with traditional methods, the practice of DSI significantly improved oxygen saturations prior to intubation. A RCT is warranted, comparing the use of DSI with the use of other techniques for achieving pre-oxygenation, when traditional methods have failed. In the mean time, on the basis of this level 4 evidence I will use the practice of DSI in selected cases
Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock
TRISS Trials Group. N Engl J Med 2014; 371:1381-1391
In patients with septic shock and managed in an ICU setting, a transfusion threshold of 7g/dl compared with 9g/dl resulted in no difference in mortality or ischaemic events. This paper supports my current practice. Avoiding unnecessary blood transfusion removes the risk of infectious, immune and non-immune related complications as well as conserving this limited resource. However, in this study 10% of patients, in the low threshold group, received transfusions despite being above the treatment threshold, therefore there may be times when the threshold needs to be modified. Patients with acute coronary syndromes were excluded from this trial. Further research is needed to assess the safety of lower haemoglobin thresholds for transfusion in these patients.
Sun: Continuous venovenous hemofiltration versus extended daily hemofiltration in patients with septic acute kidney injury: a retrospective cohort study
Critical Care 2014; 18:R70
This study does not identify any significant reasons to consider EDHF as more beneficial than the conventional CVVHF.
A large randomised, controlled trial will be needed to explore this further if the clinical question remains relevant (roughly 120 patients per group will be needed - at 80% power and alpha level of 0.05 based upon the observed primary outcome values in this study)
ARISE: Australasian Resuscitation In Sepsis Evaluation Randomised Controlled Trial
ARISE Investigators. NEJM Oct 1 2014 (ePub); DOI: 10.1056/NEJMoa1404380
Another nail in the coffin for EGDT and specifically continuous central venous co-oximetry, liberal blood transfusion policy and probably dobutamine. Despite the stark difference between ProCESS & ARISE compared with the Rivers paper, it is essential that we continue to recognise the importance of high standard of care in sepsis. Early recognition, source control, antimicrobial therapy, fluid resuscitation and escalation remain the fundamental treatment goals. I eagerly await the results of ProMISe to complete the triumvirate of modern EGDT in sepsis trials.
Chlorhexidine-Impregnated Dressing for Prevention of Catheter-Related Bloodstream Infection: A Meta-Analysis
Safdar et al. Crit Care Med 2014; 42(7): 1703-13
This meta-analysis indicates that chlorhexidine impregnated dressing may reduce CRBSI's. However, the analysis was limited by significant clinical and statistical heterogeneity. For adult ICU patients, this meta-analysis was rather unhelpful. Only two studies may be directly comparable to the generic ICU population and had low baseline CRBSI rates. However, both of these publications were by the same group with different preparations of chlorhexidine dressings. In one study, the initial skin preparation was either alcoholic chlorhexidine or alcoholic povidone- iodine based but, no subgroup analysis was made to differentiate any difference between these two skin preparations. Other study only used alcoholic providone-iodine based skin preparation. It is difficult to translate these results to centres with a lower baseline CRBSI rate (<1 per 1000 catheter days), using 2% chlorhexidine-based skin preparation.
Ferrer: Empiric Antibiotic Treatment Reduces Mortality in Severe Sepsis and Septic Shock From the First Hour: Results From a Guideline-Based Performance Improvement Program
Ferrer. Crit Care Med 2014; 38:367-374
This larger and broader observational study addresses a question that cannot ethically be answered by a randomised, controlled trial. It provides strong evidence that the time between diagnosis of severe sepsis or septic shock and the first dose of antibiotics is critical. Whether there exists a difference between 0–1 hour and 1–2 hours could be debated, but greater than 2 hours is almost certainly associated with a higher rate of hospital mortality.
Chatterjee. Thrombolysis for Pulmonary Embolism and Risk of All Cause Mortality, Major Bleeding, and Intracranial Hemorrhage - A Meta-analysis
JAMA 2014:311(23);2414-2421
Thrombolysis for PE is associated with a lower all cause mortality when compared to anticoagulation. This improvement is maintained in the subgroup of 'intermediate risk' PE with a NNT of 65. This is despite a significant increase in major bleeding in the thrombolysis group, with a NNH of 18. Of note, patients who were less than 65 years of age had no increase in major bleeding with thrombolysis.

If I have a submassive PE, I want thrombolysis (I am under 65 years of age). I would want half-standard dose as per MOPETT trial. If my Dad (he is over 65 years of age) had a submassive PE, I would not recommend thrombolysis as the 12.9% chance of major bleeding means that the risks outweigh the benefits.
PEITHO: Fibrinolysis for Patients with Intermediate Risk Pulmonary Embolism
NEJM 2014:370;1402-11
In patients with submassive PE, the administration of a bolus of tenectaplase results in only a modest haemodynamic benefit and no reducetion in 30 day mortality. Furthermore, it's use is associated with a 10-fold increase in intracranial haemorrhage (2% vs. 0.2%) and a 5-fold increase in major haemorrhage (6.3% vs. 1.2%). This study does not support the use of thrombolysis in submassive PE
TOPCOAT: Treatment of submissive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months: multicenter, double-blind, placebo controlled, randomized trial
Journal of Thrombosis and Haemostasis 2014;12:459-468
In patients with submassive PE, the use of tenecteplase resulted in a reduction in adverse outcomes based on a complicated composite outcome. However, the only independent variable that reached statistical significance was related to a self assessment of overall health at 90 days. This was simply the patients' response to being asked 'how would you rate your overall health?' (mean was 2.4 vs 3.3 out of 10). The study was small, under powered and incomplete, which limits any conclusions that can be made. I would not be persuaded to thrombolyse a patient with submassive PE based on this study.
Pearce. OPTIMISE: Effect of a Perioperative Cardiac Output-Guided Haemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal Surgery
JAMA 2014; online first 19th May
In patients undergoing major GI surgery who are over 50 years old, with risk factors for increased preoperative mortality and morbidity, using CO monitoring with an algorithm directing fluid and dopexamine therapy probably reduces the likelihood of mortality and morbidity by about 7% and possibly up to 14%, but based on this study alone there may be no clinically significant effect or no effect at all.
It is difficult to know how to generalise and apply these findings on a day-to-day basis, especially if laparoscopic surgical techniques are used.

I do not believe this provides sufficient grounds to introduce routine dopamine and 6 hours of post-operative stroke volume optimisation, but I shall continue to use CO monitoring to guide fluid therapy intra-operatively.
Waldman. Topical Tetracaine Used for 24 Hours is Safe and Rated Highly Effective by Patients for the Treatment of Pain Caused by Corneal Abrasions: A Double-blind, Randomized Clinical Trial
Emergency Medicine, 2014, 21(4):374-382
Based on this study, patients with a corneal abrasion rated topical tetracaine as being more effective than saline in providing analgesia, with no complications or delayed wound healing at 48 hours. However, the reduction of pain as measured by VAS was no different and importantly this study was not adequately powered to determine tetracaine safety. I won't be using tetracaine as routine treatment. However in situations where pain management is proving ineffective, with appropriate patient consent and local agreement, I would consider its use.
ALBIOS Study Investigators. Albumin in Patients with Severe Sepsis or Septic Shock
NEJM 2014;370(15):1412-21
The use of 20% albumin in adults with severe sepsis will improve haemodynamic indices, but will not reduce mortality. It's use is safe but not recommended for routine fluid resuscitation. Targeting a serum albumin of 30g/dl or more does not appear to confer a survival advantage
Body. The Manchester Acute Coronary Syndromes (MACS) decision rule for suspected cardiac chest pain: derivation and external validation
Heart 2014; online first 29.04.14
The Manchester Acute Coronary Syndromes (MACS) decision rule looks very promising and has the potential to help identify patients presenting with suspected cardiac chest pain that can be immediately discharged. The Manchester team are currently planning a randomised trial to compare the MACS rule with standard treatment. We eagerly await these results!
Than. A 2-hour diagnostic protocol for possible cardiac chest pain the emergency department
JAMA Internal Medicine 2014.174(1):51-58
A rapid diagnostic pathway for patients with suspected cardiac chest pain allowed earlier discharge of some low risk patients. However, further work is necessary before we can tell if this is a safe strategy, and therefore currently this strategy cannot be recommended.
Morelli. Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock – A Randomized Clinical Trial. JAMA 2013; 310(16):1683-1691
JAMA 2013; 310(16):1683-1691
The use of esmolol for tachycardic patients in septic shock resulted in good control of heart rate, and a reduction in noradrenaline dose, without any significant side effects. A large mortality benefit was reported with the use of esmolol; but with a number of study limitations, further evidence is required before a change in practice is justified
Bradford: A randomised controlled trial of induced hypermagnesaemia following aneurysmal subarachnoid haemorrhage
2013. Crit Care Resusc.15(2):119-125
This underpowered study found a non-significant reduction in vasospasm post SAH in patients treated with hypermagnesaemia. Larger trials will be required to determine if there is a significant difference and if this is results in improvements in patient-orientated outcomes.
Effect of video laryngoscopy on trauma patient survival: A randomised controlled trial
Yeatts. J Trauma Acute Care Surg 2013; 75(2):212-9
These data will help guide future research design and planned statistical analyses. The unclear risk of bias, poor compliance with recruitment and under-powered statistics means no conclusion should be drawn from these results. Further research is required to answer this important clinical question
PROSEVA Study Group. Prone Positioning in Severe ARDS
NEJM 2013;368:2159-68
Proning in severe ARDS reduces mortality without an increase in adverse outcomes. Further studies are required to confirm these findings but in the mean time these results are difficult to ignore
HOPE-ICU: Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients: a randomised, double-blind, placebo-controlled trial
Page, 2013, Lancet Respiratory Medicine, 1:7,515-523
The use of early regular haloperidol did not prevent patients developing delirium. It did reduce agitation and there was a trend towards decreased use of sedatives and analgesics when haloperidol was given. Other studies will need to tell us if haloperidol is a useful treatment once delirium has developed.
TracMan: Effect of Early vs Late Tracheostomy Placement on Survival in Patients Receiving Mechanical Ventilation
Young et al. JAMA 2013; 309:2121-2129
This trial does not provide evidence supporting early tracheostomies performed around day 4 compared to day 10 (no evidence of difference). Tracheostomy procedures are associated with a 6.3% incidence of complications requiring interventions, which must be weighed against any potential benefit. Many commentators have interpreted this trial to mean there is no benefit from performing early tracheostomies (evidence of no difference), as many will not need it if we wait until day 10. However, some patients need tracheostomies for good reasons (e.g. neurological disease) and they were not included in this study.
MOPETT: Moderate pulmonary embolism treated with thrombolysis
American Journal of Cardiology 2013:111(2);273-77
The addition of low dose thrombolysis in moderate PE decreased pulmonary artery pressure by an average of 15mmHg at 28 months. Other studies will need to tell us if this is clinically relevant. A larger study is also required to determine if this benefit is offset by the potential risks from thrombolysis
Villanueva. Transfusion strategies for acute upper gastrointestinal bleeding
NEJM 2013;368(1):11-21
Among patients with an upper GI bleed, a restrictive strategy for blood transfusion can be the standard treatment, providing, early source control with an endoscopy is achievable. The study findings are as much about highlighting the importance of 24 hour endoscopy facilities as the resuscitation management of patients with upper GI bleeding.
VSE: Vasopressin, Steroids and Epinephrine and Neurologically Favourable Survival After In-Hospital Cardiac Arrest A Randomized Clinical Trial
Mentzelopoulos. JAMA.2013;310(3):270-279
This study has shown a significant improvement for survival to discharge with a good neurological outcome following cardiac arrest when treated with combination steroids/vasopessin/epinephrine in comparison to epinephrine alone. Of note, no RCT has shown this improvement when using epinephrine alone compared with placebo. However, before introducing this into routine practice I am waiting for a validation study in a different setting. This is a single study, set in only 3 centres in 1 country. There were only 18 patients who survived with a good outcome in the intervention group. We know that a number of promising treatments have been disproven when studies have been repeated in larger trials. I hope that someone takes up the challenge of attempting to validate this trial on an urgent basis so that a more evidenced based decision can be made.
REDUCE: Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease The REDUCE Randomized Clinical Trial
JD Leuppi. JAMA 2013; 309(21): 2223-2231
It has always been my practice to prescribe short courses of steroids in COPD exacerbations and this study reinforces it.
TTM Trial Investigators. Targeted Temperature Management at 33c vs 36c after Cardiac Arrest
NEJM 2013;369:2197-206
The trial has a negative outcome and fails to show any benefit of therapeutic hypothermia at 36c over 33c after OOH cardiac arrest. Not everyone agrees this is the same as "36c is equivalent to 33c"
My conclusion: if cooling a patient to the conventional 33c induces unwanted effects, aim for 36c instead and it probably will make no difference to the patients outcome
Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial
Goodacre. Lancet Respir Med 2013; 1: 293–300
This is the largest trial looking at the role of MgSO4 in the treatment of acute severe asthma in adults. I have never used nebulised MgSO4 to treat asthma in adults and this won’t change. The use of intravenous MgSO4 in severe acute asthmatics is not without its side effects but I would still continue to use it in patients with life-threatening asthma. My expectation of achieving any significant clinical impact by giving 2g magnesium will remain low
OSCAR Study Group. High-Frequency Oscillation for Acute Respiratory Distress Syndrome
NEJM 2013;368:806-813
HFOV improved oxygenation but did not improve 30 day mortality when compared with conventional ventilation (CV) in patients with ARDS. HFOV should not be used for routine care in ARDS. The OSCILLATE trial which was published concurrently reported a lower mortality in the CV group (35% vs. 41%). One of the reasons may be that ARDSnet ventilation was mandated in OSCILLATE rather than suggested in OSCAR. Before selling your oscillator on e-bay, some may still consider it an option for rescue therapy in ARDS whilst making an ECMO referral
OSCILLATE. High Frequency Oscillation in Early Acute Respiratory Distress Syndrome
NEJM 2013.368;795-805
Patients treated with HFOV had a significantly higher mortality and therefore it should not be used as standard treatment. Refractory hyperaemia was significantly less common in the HFOV group. Further studies specifically focusing on patients with refractory hyperaemia might be beneficial, although I suspect most of us at present would prone and consider ECMO at this stage.
EUSOS: Mortality after surgery in Europe
Pearse et al. Lancet 2012; 380:1059-65
This landmark cross-sectional survey demonstrated that in-hospital mortality is higher than perceived, that unexpected variation exists across Europe, and Critical Care is poorly resourced given that many deaths happened in those that did not attend Critical Care or attended as an unplanned admission
Weekend hospitalization and additional risk of death: an analysis of inpatient data
Freemantle. J R Soc Med 2012; 105: 74-84. doi: 10.1258/jrsm.2012.120009
This study confirms an association between weekend day admissions and increased mortality within 30-days. However, in-patients are less likely to die on a weekend day than on a week day. The many confounding variables limit the conclusions that can be drawn and it should be considered hypothesis generating only. It is likely that differences in baseline characteristics between patients who are admitted at the weekend vs. weekday, account for at least part of the mortality difference found. There is no evidence presented in this study to firmly support the hypothesis that increasing senior presence and elective weekend work will reduce mortality.
Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock
IABP-SHOCK II Trial Investigators.NEJM;2012,367(14)1287-96, DOI: 10.1056/NEJMoa1208410
In patients with cardiogenic shock following acute MI, the use of IABP did not improve mortality or any longterm secondary outcome. The use of IABPs resulted in no significant increase in complications.
BEST:TRIP: A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury
Chestnut. NEJM 1012;367(26)
In patients with severe traumatic brain injury, care guided by ICP monitoring did not improve outcomes compared with management based on clinical and examination findings. Therefore I would not recommend the introduction of ICP monitoring in a resource limited setting. However, in countries such as the UK where ICP monitoring is already standard practice, I would not change practice based on this study as no harm was found, and there are significant differences in the health care provided between the UK and Bolivia/Ecuador
Prognosis of coma after therapeutic hypothermia: a prospective cohort study
Bouwes.A.,Ann Neurol. 2012 Feb;71(2):206-12. doi: 10.1002/ana.22632
In patients treated with therapeutic hypothermia following cardiac arrest the use of clinical examination at 72 hours, neuronspecific enolase and somatosensory-evoked potentials can help predict a poor outcome. The methodological limitations and wide confidence intervals mean that I would not use a single test to predict a poor outcome and will continue to use a multimodal approach as recommended by the ERC/ESICM
CHEST: Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care
Myburgh et al for the ANZICS Clinical Trials Group. NEJM 2012; 367:1901-11
This trial adds to the existing data: starch-based fluids do not provide a mortality benefit and lead to increased renal dysfunction requiring renal replacement therapy.In the context of critically ill medical and surgical patients, starch-based fluids should not be used for volume resuscitation
Davies. A multicenter, RCT computing early NJ with NG nutrition in critical illness
Critical Care Medicine 2012;40(8):2342-2348
In patients with mildly elevated gastric volumes, who are receiving ~70% of their target nutrition via a nasogastric tube, there is no advantage, and there may be harm from introducing nasojejunal feeding
PROWESS-SHOCK: Drotrecogin Alfa (Activated) in Adults with Septic Shock. N Engl J Med 2012;366:2055-64
N Engl J Med 2012;366:2055-64
DrotAA doesn’t reduce mortality in patients who are septic and you can no longer get it anyway – the drug has been withdrawn
Hagihara. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest
JAMA 2012;(307)11:1165-1168
This study found an association between the use of adrenaline for cardiac arrest, and decreased survival as well as a poor neurological outcome. It is a non-randomised study, but with >400,000 patients included it needs to be taken seriously. If this was a 'new drug' it would not be included in any guidelines and is perhaps currently still only in the guidelines because it is something that we have always done!
FEAST: Mortality after Fluid Bolus in African Children with Severe Infection
Maitland and the FEAST Trial Group, 2011, NEJM;364(26)2483-95
In an African setting, febrile children with impaired perfusion, had an increased mortality if they were treated with a fluid bolus compared with no fluid bolus. The population studied had a high incidence of malaria and severe anaemia. They were managed with a low transfusion threshold and without critical care facilities. This is very different to the population that I manage. Therefore I do not think that these results can be applied to my patients
Jacobs. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial
Resuscitation 2011;(82):1138-1143
Adrenaline increased ROSC following cardiac arrest. However there was no improvement in survival to hospital discharge or neurological outcome. Other trials have provided some evidence that neurological outcome is worse in patients receiving adrenaline. Therefore we need to support a larger trial to determine the final answer
PRORATA: Use of procalcitonin to reduce patients' exposure to antibiotics in Intensive Care Units
Bóuadma. Lancet 2010; 375:463-74. doi:10.1016/S0140-6736(09)61879-1
This trial suggests that procalcitonin-guided antibiotic therapy can reduce antibiotic administration without a significant effect on mortality outcomes
Ramachandran. Apneic oxygenation during prolonged laryngoscopy in obese patients: a randomized, controlled trial of nasal oxygen administration
Ramachandran. Journal of Clinical Anesthesia 2010;22:164-168
The addition of nasal oxygen from pre-oxygenation until post-intubation significantly prolonged the duration that oxygen saturations remained ≥95% in simulated difficult airways. There are some methodological limitations, in particular the lack of blinding. However, as those treated with nasal oxygen had such significant gains and the treatment has minimal side effects, this will become my standard practice for critically ill patients. If during RSI you have an episode of hypoxia and you have not applied nasal O2 the question should be asked as to why not.
Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury
Determann et al. Critical Care 2010; 14:R1
This intriguing and important clinical question is not sufficiently answered by this study, but it provides a suggestion that preventative lower tidal volume ventilation is best clinical practice. Further larger trials are required if clinicians feel equipoise still exists.
Strom: A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010;375:475-480
Lancet 2010;375:475-480
This study should make clinicians question the dogma of sedation in ICUs, but clinical practice should not change immediately because of this study alone. A strategy of 'no sedation' may be feasible in ICUs, but may require additional staffing. Further multi-centre trials are required with patient-centred outcomes and cost-analyses.
Initiation of Inappropriate Antimicrobial Therapy Results in a Fivefold Reduction of Survival in Human Septic Shock
Kumar. A. Chest. 2009 Nov;136(5):1237-48
In adult patients with septic shock inappropriate initial choice of empiric antibiotic therapy is associated with ~5-fold absolute reduction in survival, even after correction for co-morbidities, clinical presentation and organism. The effect size is greatest in patients with primary blood stream infections, urinary tract infections, and infections due to anaerobes or yeasts.
KETASED: Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial
Jabre et al for the KETASED Collaborative Study Group. Lancet 2009; 374:239-300
This study investigates an interesting clinical dilemma and does not demonstrate any important clinical difference in organ failure scores between ketamine and etomidate when used as a single bolus for induction. It is my impression that the likelihood of a type II error (false negative) is high in this study and there is a trend suggesting benefit from ketamine in patients with sepsis compared against etomidate
CESAR: Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure. A multicenter randomised controlled trial
Lancet 2009;374:1351-1363
The CESAR study supports ECMO as a valid treatment option for the management of patients with severe respiratory failure. However, it does not show that ECMO is better than conventional ventilation. With incomplete follow up data in nearly half of the patients and 24% of patients in the ECMO group not actually receiving ECMO, we are left with insufficient evidence as to whether ECMO is better or worse than protcolised ARDSnet ventilation in adult patients with severe respiratory failure. The study does highlight the importance of involving specialist units, effective lung protective ventilation and ECMO as an option in refractory respiratory failure.
Olasveengen. Intravenous drug administration during out-of-hospital cardiac arrest
JAMA 2009;302(20):2222-2229
The use of intravenous resuscitation medications (adrenaline, atropine and amiodarone) to patients with OOH cardiac arrest led to an increased rate of ROSC only in patients presenting in PEA/asystole. There was no improvement in survival to discharge or neurological outcome in either the shockable or non-shockable rhythm groups. A larger trial is required to determine if there is any benefit from this 'standard treatment'. This is even more important to do when other trials have found an association between the use of adrenaline and a poor neurological outcome.
NICE-SUGAR: Intensive versus Conventional Glucose Control
NEJM 2009;360:1283-97
This trial demonstrates better survival if a conventional blood glucose target of less than 10.0 mmol/L (180mg/dL) is used in critically ill patients. This trial's strong internal validity and external generalisability suggests this should be used in clinical practice in developed countries for all adult patients.
CORTICUS. Hydrocortisone Therapy in Patients with Septic Shock
NEJM 2008.;358:111-24
This study did not demonstrate survival benefit from administering hydrocortisone to adult patients with severe septic shock. It may lead to harm from superinfection. It does lead to reversal of shock quicker than placebo. Based on this study alone, hydrocortisone should not be routinely given to adult patients with severe septic shock. It may be worth considering when all else fails.
CATS Study: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial
Lancet 2007;676-84
There was no significant difference found between the use of adrenaline vs. noradrenaline ± dobutamine in patients with septic shock. However, the study was under-powered and with a trend towards harm in the adrenaline group, highlights the need to conduct larger studies before considering adrenaline as the first agent for the management of septic shock. I will continue to reach for noradrenaline for patients with septic shock. The study does provide some reassurance that adrenaline infusion is a reasonable alternative in the early phase of shock or in resource limited settings.
ABC trial: Efficacy and Safety of a Paired Sedation and Ventilator Weaning Protocol for Mechanically Ventilated Patients
Girard. The Lancet 2008; 371:126-134
The use of SATs during this trial appears to expedite weaning from mechanical ventilation, but the study findings may potentially reflect greater levels of oversedation in the control group or a bias towards early extubation in the intervention group. Their use may be associated with greater risk of self-extubation and increased nursing workload
Meduri. Methylprednisilone Infusion in Early Severe ARDS
Chest 2007;131:954-63
Patients with ARDS should not be given early methylprednisilone on this study alone due to methodological concerns
Kumar. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock
Kumar. Crit Care Med 2006; 34 (6):1589-1596.
This study is a landmark paper in critical care practice. The message is powerful. Early and appropriate antibiotic therapy saves lives. The methodology of the paper is not without some significant limitations but a randomised controlled trial is not likely to ever occur now. Source control and early appropriate antibiotics will remain an integral part of the Surviving Sepsis Campaign.
PAC-MAN: Pulmonary Artery Catheters in patient Management
PAC-MAN study group, Lancet 2005;366;472-477
In units that practice PACs on a regular basis for critically ill patients, there was no benefit found from the use of a PAC. Complications occurred in 10%, although some of these may have been avoided with the use of ultrasound. Subgroup analysis showed no benefit in any 'major presumptive clinical syndrome,' however like with all studies, subgroup analyses were not sufficiently powered to give us the definite answer. Historically, the majority of ICUs that took part in the study used PACs frequently. Current practice means that a number of units use PACs very infrequently, much less than 5% which was the cut-off in the study for 'low use of PAC'. With unfamiliarity the benefits from the use of a PAC may be less and the complications may be greater.
SAFE Study Investigators. A comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit
NEJM 2004;351:1905-1908
Overall there is no difference when 4% albumin is used for fluid resuscitation when compared with 0.9% sodium chloride. 4% albumin should be avoided in head injuries. A further study in patients with severe sepsis and septic shock would be beneficial - hence the ALBIOS study
CRASH-1: Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury: randomised placebo-controlled trial
Roberts et al for the CRASH trial collaborators. Lancet 2004; 364:1321-28
Corticosteroids should not be given to patients with head injuries, unless other specific indications exist that outweigh the increased risk of death demonstrated by this trial
Bouderka: Early tracheostomy versus Prolonged Endotracheal Intubation in Severe Head Injury
J Trauma: Injury, Infection & Critical Care 2004;57(2): 251-254
This small study found no convincing benefit from early tracheostomy when compared to prolonged endotracheal ventilation in patients with severe head injury. Further larger studies are required. Critical appraisal of trials is paramount - don't just read the abstract and conclusions of trials!
Effects of selective decontamination of digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial.
De Jonge Lancet 2003; 362: 1011–16
The use of SDD continues to divide opinion amongst ICU clinicians – concerns remain over its beneficial effect on patient mortality and the promotion of antibiotic resistance. The fact that the study population had low prevalence of VRE and MRSA would limit its application. My view is exactly that of the SuDDICU study – I would be prepared to introduce SDD in the context of a clinical trial.
MAPPETT 3: Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism
NEJM 2002:347(15);1143-1150
Thrombolysis for sub-massive PE decreased the requirement for rescue thrombolysis but did not affect mortality or adverse events i.e giving thrombolysis early meant that you were less likely to need to give it later. Further evidence if required before this treatment is recommended
Annane: Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock
JAMA 2002; 288:862-871
The two biggest studies regarding the use of steroids for septic shock have found conflicting results. On the basis of these studies I will not use steroids as routine for patients with septic shock due to the potential side effects. However in patients that are not responding to treatment and are at high risk of death, I will continue to use steroids as some benefits have been reported. I will not base my decision on the corticotrophin result as other studies have reported a number of limitations with using this test in critically ill patients. I eagerly await the results of the ADRENAL study which will hopefully allow a more evidenced based decision to be made.
Kress. Daily Interruption of Sedative Infusions in Critically Ill Patients Undergoing Mechanical Ventilation
NEJM 2000;342:1471-1477
In ICUs (especially medical ICUs) that target moderate depths of sedation (Ramsey > 3 or RASS < -1) with continuous infusions of drugs, daily sedative interruptions will probably reduce the period of mechanical ventilation and ICU LOS. I believe the methodological flaws in this study exaggerate the positive effect size, and it is underpowered to say that daily sedative interruptions are safe and without psychological harm
Bellomo: Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial
Bellomo et al. Lancet 2000; 356:2139-2143
There is no place for dopamine to prevent renal dysfunction from getting worse in patients with SIRS
ARDSnet Investigators. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome (ARMA)
NEJM 2000;342:1301-1308
Adult patients with acute lung injury or acute respiratory distress syndrome should be ventilated with tidal volumes of 6ml/kg, limiting plateau pressures to 30cm water
Herbert and TRICC Investigators: A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care
NEJM 1999;340-409-417
The transfusion threshold in critically ill patients can be between 7-9g/dl without adverse effects. Compared with the previously higher (>9g/dl) threshold, this results in less blood transfusions and its associated costs and potential complications. Caution has been advised in patients with evidence of active cardiac ischaemia
Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome
Meduri. JAMA 1998; 280(2):159-165
The use of methylprednisolone in ARDS is controversial. We know that its early use is associated with harm. This study looking at its use from day 7 after diagnosing ARDS was underpowered and included heterogenous causes for the development of ARDS. With improvements in lung protective strategies and overall mortality for ARDS on the decline, the role of steroids is perhaps less relevant. The difficulty is predicting the patient group that end up with established fibrotic lung disease where steroid therapy in theory may have helped. Radiological surveillance, respiratory specialist input and confirming no evidence of infection is essential before considering its use. A RCT which is powered to detect an improvement in one year mortality and lung function is required.
Comparison of rocuronium and suxamethonium for use during rapid sequence induction of anaesthesia
McCourt. Anaesthesia 1998;53:867-871
In patients undergoing a RSI, who were not anticipated to have a difficult airway, 1mg/kg suxamethonium and 1mg/kg rocuronium produced similar clinically acceptable intubating conditions. Suxamethonium was more likely than rocuronium to produce 'excellent' intubating conditions and is one of the reasons it is preferred by some clinicians. Whether this benefit would make a significant difference in patients with anticipated difficult airway and where 'wake up' is not an option is beyond the scope of this study. Rocuronium seems to be increasingly favoured in this situation as it provides similar early onset of muscle relaxation but lasts longer than suxamethonium. This may provide better conditions to allow ongoing airway management and if necessary progression to a surgical airway.
Sellick: Cricoid pressure to control regurgitation of stomach contents during induction of anaesthesia
Sellick BA. The Lancet 1961, Volume 278, Issue 7199, Pages 404-406
There is no empirical evidence supporting the use of cricoid pressure (CP) beyond this single case series and expert opinion (grade 4-5 evidence). Those advocating its use, emphasise the associated high mortality rate if aspiration occurs. Opposition point to the poor evidence for improved safety and potential harm with CP. This includes making it harder to intubate and ventilate if the anatomy of the glottis becomes distorted as well as decreasing oesophageal tone (which may actually increase the risk of regurgitation)
The Difficult Airway Society (DAS) are revising their guidelines for 2015 and I hope will begin to de-emphasise the overstated evidence base for CP use in RSI.
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