Trials Flashcards
ALBIOS
2014 n= 1800 Italian
Severe sepsis or septic shock
Does keeping albumin >30g/L improve mortality
No difference in 28 or 90 day mortality
Albumin group less time on vasoactive drugs and improved CVS parameters earlier in admission
No difference in SOFA score
Higher incidence on coag and liver dysfunction in albumin group
TRICS III
cardiac surgery patients
restrictive vs liberal transfusion practices
Restrictive was non inferior
- patients ok with Hb down to 75
LeoPARDS
2017
n = 500, multicentre
use of levo in sepsis
No improvement in mortality or SOFA scores
increased risk of arrythmias and longer MV
EAT ICU
2017
does early goal-directed nutrition (EGDN) during ICU stay compared to standard care nutrition delivery result in improved physical quality of life at 6 months
n = 200, single centre
used indirect calorimetry and urinary urea excretion to calculate needs, and 100% provided (with EN +PN as needed)
No difference in outcomes at 6/12
RECONNECT
OUtcome - In critically ill patients who pass a spontaneous breathing trial, reconnection to a ventilator for 1-hour compared with immediate extubation, significantly reduced the rate of re-intubation within 48 hours.
However - very underpowered
DETO2X - AMI - use of oxygen in suspected MI patients
n =>6000
Question - In patients with suspected myocardial infarction with no baseline hypoxia (sats >90%), does oxygen therapy or room air improve all-cause mortality at 1 year?
patients given 6l/min for 6-12hrs vs air
- supplemental oxygen made no difference to outcomes in normoxic patients with suspected AMI
- This result combined with other recent studies that have suggested potential harm from oxygen, plus the fact oxygen is not free, suggests that oxygen therapy in this population is no warranted
IVC collapsability in spont breathing critically ill and fluid responsiveness
Background - Assessing the collapsibility (or distensibility if the patient is mechanically ventilated) of the IVC during respiration using point of care ultrasound (POCUS) has been recommended by some clinicians as a means to assess fluid responsiveness, however this is controversial
Did find it identified patients who resonsded, BUT was a poorly deigned study with bad methodology
Use of HFNP in high risk patients following extubation
Background -
Hernandez has previously demonstrated that in low risk patients the risk of re-intubation can be decreased with the use of high-flow nasal oxygen post-exubation
Nava and Ferrer reported that in high risk patients, the use of post extubation non-invasive ventilation can reduce re-intubation rates and respiratory failure
Bottom line -
- This randomised controlled trial demonstrated that in patients that are high risk for re-intubation the use of high flow nasal oxygen was non-inferior to non-invasive ventilation
My practice -
In patients that are high risk for re-intubation I will use non-invasive ventilation, and if this not tolerated then change to high flow nasal oxygen
TRICOP
Restrictive vs liberal transfusion in cancer patients
No difference in 28 or 60 day mortality, but a difference in 90 days (BUT fragility index of 0)
ATHOS III
NEJM 2017
In patients with refractory vasodilatory shock does the addition of angiotensin II improve blood pressure compared with standard vasopressor therapy?
Bottom line -
Angiotensin II increases blood pressure in patients with vasodilatory shock
Numerically patients were less likely to have adverse events and die compared with the control group
This trial is likely to make angiotensin II available (the trial was conducted in consultation with the FDA)
DESIRE
Question - In ventilated patients with sepsis, does a sedation strategy with dexmedetomidine compared with no dexmedetomidine improve mortality and number of ventilator-free days?
The Bottom Line
In ventilated patients with sepsis or pancreatitis, this study fails to demonstrate a significant impact of dexmedetomidine on 28-day survival or ventilator-free days but was likely underpowered for mortality.
Levosimendan for Hemodynamic Support after Cardiac Surgery
Landoni. NEJM 2017
In patients undergoing cardiac surgery with peri-operative left ventricular dysfunction, it appears that a low-dose infusion of levosimendan is not beneficial
NB - didn’t use bolus, used much smaller doses for infusion
Levo CTS
Used prophylactically in CTS patients with LVEF <35%
Levosimendan does not have any clinical outcome benefit, when used as a prophylactic agent, in patients with poor left ventricular ejection fraction undergoing cardiac surgery on bypass
- used a low dose infusion and small bolus
Use of NIV upto 7 days after abdominal surgery in those who develop respiratory failure
Patient with hypoxia and acute resp distress up to 7 days after surgery
In this trial, 6 hours of low-level non-invasive ventilation in patients with acute hypoxic respiratory failure after major abdominal surgery reduced the need for re-intubation compared to standard oxygen therapy
no clinically relevant harm or intolerance was identified and therefore this paper will change my practice
Further studies comparing this strategy to high-flow nasal oxygen therapy are urgently needed
PRESERVE
NEJM 2017
high risk patients having interventional radiology
Does NAC or bicarb improve outcome
NO
terlipressin in cirrhosis and septic shock
In patients with cirrhosis and septic shock, this single centre non-blinded RCT demonstrated that terlipressin in comparison with noradrenaline improved haemodynamics and had a mortality benefit. Due to a number of methodological flaws and baseline differences I would want further evidence before this becomes standard practice.
Hybernatus
Hypothermia for Neuroprotection in Convulsive Status Epilepticus NEJM 2016
Intervention
Target core temperature of 32 to 34°C as rapidly as possible post randomisation
Target temperature maintained for 24 hours
Conclusions
In critically ill patients with convulsive status epilepticus receiving mechanical ventilation, the addition of therapeutic hypothermia to standard antiepileptic therapy showed no significant benefit with respect to good functional outcome
Dexmedetomidine for prevention of delirium in elderly (>65 yrs) patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial
Study drug started - low dose Dexmedetomidine
0.1mcg/kg/hr
If extubated: usually within 1 hour of admission to ITU post-operatively
If intubated: once sedation titrated to Richard-Agitation Sedation Score (RASS) -2 or higher
This study demonstrates an impressive reduction in post op delirium with low dose Dexmedetomidine infusion. Further studies needed to clarify if these results can be applied to a wider range of patients, and also to rule out possible safety concerns.
Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients – RENAL trial NEJm 2009
Delivering higher intensity dialysis dosing is not without risk. Some of the potential disadvantages are; disturbance in electrolyte concentrations, increased costs and nursing workload, micronutrient depletion and subtherapeutic levels of antibiotics.
This is the best trial examining ‘dose’ of dialysis in critically ill patients and stands the test of time, even 8 years after publishing. I will continue my practice of dialysing critically ill patients with AKI at 25ml/kg/hr.
Normal Oxygenation Versus Hyperoxia in the Intensive Care Unit (ICU) (OXYGEN-ICU)
Giradis. JAMA 2016
Question - In critically ill adults, does conservative oxygen therapy compared to liberal oxygen therapy reduce mortality?
94-98% vs >97%
Significantly lower mortality in conservative group
- need a larger RCT, avoid hyperoxia?
PATCH lancet 2016
In patients with acute intracerebral haemorrhage, associated with antiplatelet therapy, does platelet transfusion compared with standard care reduce death or dependence?
No - worse outcomes (small trial, but still…)
RESCUE ICP
Inclusion: patients with a TBI with an abnormal brain CT and raised intracranial pressure of >25mmHg for 1-12 hours, despite stage 1 and 2 measures; aged between 10 and 65 years
Intervention
Decompressive craniectomy
Continued stage 1 and 2 treatments plus decompressive craniectomy
Either large unilateral fronto-temporoparietal craniectomy (hemicraniectomy) for patients with unilateral hemispheric swelling or bifrontal craniectomy for patients with diffuse brain swelling
Improved mortality but worse functional outcome
EUROtherm3235
NEJM 2015
Clinical Question
In patients with traumatic brain injury (TBI), does hypothermia (32-35°C) and standard care compared to standard care alone reduce death and major disability at 6 months after injury?
In patients with ICP >20mmHg after TBI Cooling leads to worse mortality and functional outcome
VANISH NEJM 2016
Clinical Question
Does early vasopressin use reduce the risk of kidney failure in patients with septic shock compared with norepinephrine?
Study drug 1
Vasopressin (titrated up to 0.06 U/min) or Norepinephrine (titrated up to 12 μg/min)
Study drug 2
Hydrocortisone (50mg 6 hourly and then weaned) or Placebo
Bottom line -
- vasopressin does not reduce the number of renal replacement free days or mortality rate, and there was no clinical interaction with corticosteroids
Procainamde vs amioderone in tretment of HD tolerated wide complext tachycardia
The results of this trial suggest an improved safety profile and efficacy of 10mg/kg intravenous procainamide over 20mins when compared with 5mg/kg intravenous amiodarone over 20mins in tolerated wide complex tachycardia.
Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage
NEJM 2016
Clinical Question
In patients with acute intracerebral haemorrhage and who are hypertensive, does rapid lowering of systolic blood pressure compared to standard therapy improve patient outcomes ?
Target systolic BP 110 to 139 mmHg throughout the 24 hours after randomisation
vs
Target systolic BP 140 to 179 mmHg throughout the 24 hours after randomisation
The Bottom Line
The results of this trial and that of the INTERACT2 trial do not support an early, intensive control of systolic blood pressure in patients with acute intracranial haemorrhage
ELAIN-
Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury
JAMA 2016
Intervention
Initiation of RRT within 8 hours of confirmation of KDIGO stage 2
Control
- Inititation of RRT within 12 hours of either
KDIGO stage 3 criteria
Creatinine rise >3 fold increase from baseline, or oliguria <0.3ml/kg/hr for ≥24 hours or serum creatinine > 4mg/dl (353.6 μmol/l) with an acute increase of at least 0.5mg/dl (44.2μmol/l) within 24 hours
Absolute indication for RRT
Urea >100mg/dl
Potassium >6mmol/l and or ECG abnormalities
Magnesium >4mmol/l and/or anuria/absence of deep tendon reflexes
Blood pH <7.15
Urine production <200ml/12hr or anuria
Organ oedema in the presence of AKI resistant to diuretic treatment (defined as one trial of furosemide)
This single centre study demonstrates a significant reduction in 90 day mortality with early (stage 2 KDIGO) initiation of RRT, in a group of almost entirely surgical patients.
However, other evidence is conflicting
AKIKI NEJM 2016
Initiation Strategies for Renal-Replacement
Therapy in the Intensive Care Unit
Clinical Question
In critically ill patients with acute kidney injury does delayed compared with early initiation of renal replacement therapy (RRT) reduce mortality at 60 days?
The Bottom Line
In critically ill patients with severe acute kidney injury, an early approach to RRT did not provide a mortality benefit compared to a delayed approach; when the RRT modality was predominately intermittent RRT.
~50% of the patients in the delayed group did not receive RRT
There was a significantly higher rate of catheter related nosocmial infections in the early group
DahLIA
Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients with Agitated Delirium. A Randomized Clinical Trial
. JAMA 2016
Inclusion: Adult ICU patients who needed to remain mechanically ventilated because their degree of agitation was considered so severe as to make lessening their sedation and extubation unsafe
Bottom line -
This underpowered study showed potential benefits of using dexmedetomidine, in addition to standard care, for ventilated patients with agitated delirium, who are otherwise ready for extubation. In particular, there was a modest reduction in time for liberation from the ventilator, more rapid resolution of delirium and sedation and opioid sparing effects.
ART
Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial JAMA 2017
In patients with moderate-to-severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality
These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients.
Done is south america
Use very high recruitment (upto 45cmH2O of PEEP)
ATACAS TXA
Tranexamic Acid in patients Undergoing Coronary-Artery Surgery
N Engl J Med 2017
TXA 100mg/kg
Administered intravenously
30 minutes after induction
Dose reduced to 50mg/kg in January 2012 (1392 patients enrolled, 758 given TXA) as seizures reported and this was felt to be dose related
This trial provides valid reason to consider using TXA in elective patients undergoing elective coronary artery surgery to reduce the blood product requirements, however it may increase post-operative seizure incidence
SHENFU critical care medicine 2017
This large multi-centre randomised controlled trial demonstrated a significant reduction in mortality with the use of Shenfu following in-hospital cardiac arrest, with a number needed to treat of 8
This compares to a NNT of 6 for the original HACA therapeutic hypothermia trial
The sceptic in me tells me that if something appears too good to be true then it probably is
My concerns regarding the lack of blinding, the differences in baseline characteristics, the variation in compliance with the post-resuscitation bundle and the fact that the study was performed in a single country means that I want to see more evidence before I start using Shenfu in my practice.
TTM 48 JAMA 2017
In adults with out of hospital cardiac arrest (OOHCA) due to a presumed cardiac cause, who are post ‘return of spontaneous circulation’ (ROSC), does cooling to 33°C for 48 hours, compared with 24 hours, improve improved neurological outcomes at 6 months?
No improved outcome
High incidnce of hypotension and longer length of stay
I will continue to control temp for 24 hours following OOHCA
INSTINCT intensive care medicine 2017
Clinical Question
In patients with necrotising soft tissue infection (NSTI), does the use of intravenous immunoglobulin (IVIG) compared to placebo improve patient reported physical outcomes?
Background
IVIG consists of pooled plasma from 2000-10000 donors with the IVIG fraction
IVIG has anti-infective and immunomodulatory properties. It inhibits the activity of streptococcal and staphylococcal virulence factors
NSTI’s are characterised clinically by fulminant tissue destruction, systemic signs of toxicity, and high mortality
Type 1: Polymicrobial: Anaerobic e.g. clostridium, non GAS, E Coli, klebsiella etc.
Type 2: Monomicrobial (GAS most common), staphylococcus, MRSA
Prior to INSTINCT, The effects of IVIG vs placebo have been assessed in only one small RCT. This was stopped early because of slow recruitment rate (21 patients). The evidence base for IVIG therefore comes mainly from retrospective studies
Negative study
This study does not demonstrate a statistically significant difference in patient centred outcomes when IVIG is used in combination with surgery, antimicrobials and hyperbaric oxygen
Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ Failure
Timsit J-F. JAMA 2016
Clinical Question
In critically ill patients with non-neutropenic sepsis, multiple Candida colonisation and multi organ failure, does empirical micafungin therapy increase invasive fungal infection-free survival at day 28 compared with placebo?
This study does not support empirical anti-fungal therapy with micafungin in a select group of intensive care patients at high risk of invasive candidiasis
Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy
The Lancet 2017
Clinical Question
In high-risk patients receiving contrast medium, does prophylactic hydration with normal saline compared to no prophylaxis impact the rate of contrast-induced nephropathy?
Intervention - Hydration Group:
3–4 ml/kg/hr of normal saline for 4 hours before and after contrast OR 1 ml/kg/hr of normal saline for 12 hours before and after contrast
Control - No hydration
Authors’ Conclusions
No hydration was non-inferior to hydration in the prevention of contrast induced nephropathy. Hydration is more expensive and can cause problems in itself. HOWEVER - does not specify ICU patients; therefore, at this stage, intravenous hydration in this population should continue especially if the patient has haemodynamic instability, nephrotoxic drugs and high contrast doses. Patients with GFR < 30 should still receive peri-procedure hydration. With patients at risk of pulmonary oedema, hydration should be used judiciously.
Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial
. Lancet Resp Med 2015
Intervention - Restricted caloric management group
20 kcal/h for at least 2 days and then a gradual return to normal intake protocol over the following 2-3 days
Restrictive caloric intake for refeeding syndrome did not statistically increase the number of days alive after ICU. However it did increase two clinically important components of this composite measure, survival time and 60-day mortality. In addition there were fewer respiratory infections. I will continue to use a restrictive caloric feeding regimen whilst treating refeeding syndrome
Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock
Crit Care Med. 2015
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.
Recovery after critical illness in patients aged 80 years or older
] Intensive Care Medicine 2015
Prospective cohort study in canada
The Bottom Line
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.
Air Versus Oxygen in ST-Segment Elevation Myocardial Infarction
AVOID. Circulation 2015
Clinical Question
In patients with ST-elevation-myocardial infarction (STEMI), without hypoxia, does receiving supplemental oxygen compared with no supplemental oxygen reduce early myocardial injury?
Intervention - Oxygen group; Patients received supplementary oxygen via face mask at 8L/min
Control group - no oxygen until sats <94%
The Bottom Line
This trial fails to show any benefit in giving oxygen to normoxic patients with STEMI undergoing PCI and may in fact cause harm
PermiT: Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults
NEJM 2015
40–60% vs 70-100% of caloric requirement
- both had full protein diet
The bottom line -
Permissive underfeeding with full protein requirement appears safe in critically ill patients
FLORALI: High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure
NEJM 2015
Clinical Question
In patients with acute hypoxaemic respiratory failure, does high-flow oxygen through nasal cannula, compared with standard oxygen delivered through a facemask or non-invasive positive-pressure ventilation, prevent intubation?
The Bottom Line
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.
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. The PROPPR Randomized Clinical Trial
PROPPR Study Group*, JAMA. 2015
The Bottom Line
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.
Refractory cardiac arrest treated with mechanical CPR, hypothermia, ECMO and early reperfusion (the CHEER trial)
Resuscitation January 2015
Clinical Question
In patients who are in refractory cardiac arrest (>30mins, VF arrest if OOH, anything if in hospital), does protocolised management involving mechanical CPR, Hypothermia, ECMO and early reperfusion improve survival rate?
Single centre, australia
54% survival with good neurological outcome
The Bottom Line
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
N Engl J Med 2014
Clinical Question
In patients with severe pancreatitis, does early enteral feeding compared with on-demand feeding reduce death or major infection?
Intervention - “Early” group:
Nasojejunal tube placed within 24 hours of randomisation and feeding commenced
Tubes placed endoscopically or radiologically
Feeding was started at 20ml/hr for the first 24 hours, then 45ml/hr from 24-48 hours, then 65ml/hr from 48-72 hours, and full feeding based on actual body weight after this
Control - “On-demand” group:
Oral diet was provided at 72 hours
Supplementation by tube feeding after further 24 hours if unable to tolerate oral intake
Prior to this received only IV fluids unless they requested oral food
The Bottom Line
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
Clinical Question
In older patients with malignant middle cerebral artery infarction does early hemicraniectomy, compared with standard care, improve survival without severe disability?
The Bottom Line
In older patients (>61) 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.
Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock
TRISS Trials Group. N Engl J Med 2014
The Bottom Line
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.
Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage – A Meta-analysis
2014 JAMA
The Bottom Line
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 ≤65 years had no increase in major bleeding with thrombolysis.
With the MOPETT and TOPCOAT studies finding improved longterm outcomes with regards to pulmonary hypertension, and self assessment of overall health in the thrombolysis groups, this meta-analysis provides a convincing argument for the use of thrombolysis in submassive PE.
If I have a submassive PE, I want thrombolysis. (I am under 65 years). I would want half-standard dose as per the MOPETT trial. If my dad (he is over 65 years) had a sub-massive PE I would not recommend thrombolysis as the 12.9% chance of major bleeding means that the risks may outweigh the benefits.
SEPSISPAM: High versus low Blood-Pressure Target in Patients with Septic Shock
NEJM. 2014;
Intervention - target MAP 80-85, for maximum of 5 days or until weaned from vasopressor support
Control - target MAP 65-70
The Bottom Line
For the majority of patients in septic shock a target MAP of 65-70 is a good starting point. However, in patients with chronic hypertension I will target a higher MAP. This is because, even though this did not improve mortality, it did reduce the need for renal replacement therapy with a NNT of 9.5. A number of studies have previously demonstrated that the need for renal replacement therapy is associated with mortality.
In patients without hypertension further studies comparing a MAP of 65 with a lower MAP of e.g. 55 would be beneficial
BEST:TRIP: A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury
Chestnut. NEJM 2012
The Bottom Line
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.
TracMAN JAMA 2013
The Bottom Line
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.
Efect of Intensive vs. Moderate Alveolar Recruitment Strategies Added to
Lung-Protective Ventilation on Postoperative Pulmonary Complications. A
Randomised Clinical Trial. JAMA 2017
PEEP 13 vs 8
CTS patients
Higher PEEP group did better
Should we routinely use recruitment maneuvres as described in this trial to prevent post operative pulmonary complications?
Possibly. In contrast to the open lung strategy employed by the ART trial, a more
conservative approach was successfully used in this trial. Further data is required to
clarify the role of recruitment maneuvres in ventilatory management.
Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med
2017
a single-centre, randomised controlled trial comparing APRV against low tidalvolume
lung protective ventilation (LTV) in patients with ARDS conducted in the West
China Hospital of Sichuan University, China
Patients in the APRV group had signifcantly more VFDs by day 28 than those in the LTV
group
More patients receiving APRV were successfully extubated and fewer required tracheostomy
There was no difference in the incidence of pneumothorax; 3 vs. 7 in the APRV vs LTV groups, respectively (P = 0.199). Neuromuscular blockade, prone
positioning, nitric oxide or HFOV was required in 23 (34%) patients in the LTV arm and 6
(8%) receiving APRV. Length of stay was signifcantly reduced in ICU
NUTRIREA-2 trial
Included more unwell patients than calories (had to be MV)
No differences EXCEPT;
provides new cautionary evidence against early enteral nutrition due to gastrointestinal complications. The rates of vomiting, diarrhoea and psuedo-obstruction were statistically higher, but most alarming was the four-fold increase in bowel ischaemia (5 patients in the parenteral group vs. 19 patients in the enteral group, P = 0.007)
Should we routinely choose initial parenteral rather than enteral nutrition in haemodynamically unstable critically ill patients?
Possibly. Although parenteral nutrition offers no survival beneft over enteral nutrition
in this setting, its use results in less gastrointestinal complications, a fnding seen in two
major randomised controlled trials
CALORIES tria
n = 2,388 patients were randomised to parenteral (n = 1,191) or enteral (n = 1,197) nutrition, commenced within 36 hrs of ICU admission and continued for 5 days
Nutritional targets were set at 25 kcal/kg/day.
Neither group met nutritional targets.
Overall mortality was 33.1% in the parenteral group and 34.2% in the enteral group
Hypoglycemia was less frequent in the parental nutrition group (3.7% vs. 6.2%; P = 0.006), as was vomiting (8.4% vs. 16.2%; P < 0.001).
There were no differences in infectious complications or other outcomes.
Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial.
Lancet Respir Med 2017;5(3):180-190
Trial stopped early due to harm from both internvention
Hyperoxia has shown no beneft and may well be harmful. Hypertonic saline, as used, didn’t reduce overall fuid volumes and was predictably limited by hypernatraemia.
Biomarker based strategy for early discontinuation of empirical antifungal treatment in critically ill patients: a randomised controlled trial. Intensive Care Med
2017;43:1668-1677
- guideline for empirical antifungal prescription stipulated patients had to be suffering a persistent fever, for greater than 48 hours, despite antibiotics and exhibit signs of haemodynamic instability in the last 12 hours, and also had to fulfl at least one major and two minor criteria, as outlined below;
Major Criteria - Systemic antibiotic therapy, Total parenteral nutrition
Minor Criteria - Central venous catheter, Dialysis, Major surgery, Pancreatitis. Use of corticosteroids
Intervention group had serum levels of (1,3)-ß-D-glucan,
mannan and anti-mannan antibody measured on day 0 and day 4
Significnatly more patients in intervention group had antifungals ceased
No increased cases of invasive candida
NB - very small study
DEXILIRIUM
Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective
Noncardiac Surgery - A Randomized Clinical Trial. JAMA Surg
Pts >68 yo given intra op dexmed
No differnce in peri-operative delirium and post-operative cognitive dysfunction (POCD)
DAWN NEJM 2018
Included if they had evidence of occlusion of the intracranial internal carotid artery, the frst section of the
middle cerebral artery, or both on CT angiography or MR angiography, and they had a mismatch between imaging and clinical severity of stroke, in addition to an absence of haemorrhage and a good premorbid level of function.
Outcomes -
For every 2 patients who underwent thrombectomy, 1 patient had less disability at 90 days compared with the control group. For every 2.8 patients who underwent
thrombectomy, 1 more had functional independence at 90 days than in the control
group
TRIBE
Transfusion Requirement in Burn Care Evaluation – A Multicentre Randomised Prospective Trial of Blood Transfusion in Major Burn Injury. Ann Surg
2017;
examined whether a restrictive transfusion policy would reduce bloodstream infection (BSI), organ dysfunction and mortality in critically ill burns patients, within 96 hours of injury and suffering ≥ 20% total body surface area burns (TBSA)
randomised to either a restrictive (target haemoglobin, Hb, 70 – 80 g/L) or a liberal transfusion strategy (target Hb 100 – 110 g/L) for the duration of their hospital
admission
No differences between groups
