The Talk!
I presented my TOP 10 LIFESAVING PAPERS in critical care at the Manchester Crit Care Symposium Last week.
Which papers made it in? Why? What did they change for ICU care?
Lets take you on a little journey!
How did I come to the top 10 then?
I went on:
- Citation count – reflects long-term academic influence Then looked at:
- Altmetrics – ongoing real-world discussion on Socials, on blogs and from meetings We will break down the chosen papers with reference to these systems
So, how have we evolved over the years on ICU?
How have we influenced outcome and mortality?
What have we done that’s been so groundbreaking to make the sickest, less so?
There are a wealth of studies in critical care … most of which we hope will have positive outcomes in amongst such a difficult heterogenous population!
So…
Paper number 1!
Remember when we did whatever we wanted with ICU care
Much akin to treating the patient like a lab guinea pig! – Chuck in a bit of this and a bit of that; willy nilly!?
Along came…
Who’d have thought tight targets would lead to better outcomes?! – ICU became like a crazed game of medical darts!
- CVP, MAP, ScvO₂
- Fluids everywhere
- Vasopresors being dribbled in
- Blood by the bucketload
- So much oxygen!
What didn’t it change?
- Reduced in-hospital mortality in sepsis
- Raised awareness + production of Sepsis bundles
- Transformed sepsis from a reactive ICU issue into an emergency requiring immediate, aggressive, protocolised care in the ED/early hours
- Earlier recognition, fluids, antibiotics, and source control!
Rivers was a hero!
But!
- >5–6 L in the first 6 hours, averaging ~13 L over 72 hours!
- Increased dobutamine use (arrhythmia risk)
- Blood transfusions (transfusion-related risks) (Led to trials)
Positive fluid balance turned out to be independently linked to worse outcomes including
- Prolonged ventilation, AKI, longer ICU stays, and higher mortality.
ProCESS, ARISE, ProMISe, PRISM happened – no added benefit over improved “usual care.”
However…
- There was an inordinately high control-group mortality raising external validity concerns.
- Possibly over-manned by Manni himself?
- ED population so not transferrable to ICU?
Gamechanging?
Yep! – It formed the foundations and core of the SSC bundles (bar the IV Resus dose of fluids!)
It certainly paved the way to FLUID STEWARDSHIP
Not a keeper…but a helpe
Paper No. 2
Remember when our ICU patients had such high blood sugars, you could spread it on toast as a sweet treat!
In the summer, your unit became a Mecca for honey bees! – Sugar was so good for you, after all, it fuels the cells!
Then came…
Intensive Insulin Therapy in Critically Ill Patients (Leuven Surgical ICU Trial) – 2001
Who’d have thought restricting the fuel would end the duel…with sepsis?! This paper popularised tight glucose control (often 80–110 mg/dL) The results demonstrated reduced mortality and morbidity from infections, renal failure, polyneuropathy etc in surgical ICU patients
What did it change?
- Widespread adoption of tight insulin protocols.
- Led to a major shift away from tolerating marked hyperglycemia.
But
- Associated complications (e.g., seizures, neuroglycopenia)
The single-centre Leuven results were never fully replicated in multicentre settings, highlighting issues with generalisability, nutritional differences, and monitoring intensity.
Then a large multi-centre trial happened NICE-SUGAR which showed:
- Increased 90-day mortality with intensive insulin therapy driven by hypoglycemia.
- Moderate control adopted (typically <180 mg/dL or 140–180 mg/dL) to balance benefits and risks.
So – we park this one…not quite the ‘Bees knees!’
Paper No. 3
Remember when we used to blow our patients up like a child’s party balloon!
Remember when we thought Bar-otrauma was the result of an alcohol fuelled fight in a pub that didn’t end well?!
hen comes:
Who would have thought ventilating a patient with a laughable amount of tidal volume would actually help!
It established lung-protective ventilation (6 ml/kg predicted body weight, plateau pressure ≤30 cmH₂O)
It reduced in-hospital mortality from 39.8% to 31.0%, increased ventilator-free days amongst ARDS and soon, all ventilated patients!
What did it change
It ended the era of high tidal volumes (10–12 ml/kg)
Lung protective and low plateau pressure ventilation became the mantra!
Remains core today!
But
- Rigid application out of context in non-ARDS patients (e.g. Hypercarbic respiratory failure) caused atelectasis, worsened hypoxemia, increased dead-space ventilation, decreased alveolar hypoventilation requiring higher PEEP or sedation and discomfort in some cases
- Early post-trial implementation sometimes led to transient worsening of gas exchange before improvement.
It remains the no. 1 most referenced ARDS/ventilation paper – Strong sustained altmetrics for a 25+ year-old study due to ongoing influence.
A keeper!!
Paper No. 4
Remember when we just plugged patients into the vent
We struggled to explain why the lungs were so broken!
The lungs were just…well, stuffed to be honest!
Then came Berlin!
Acute Respiratory Distress Syndrome: The Berlin Definition – 2012
Who’d have thought a classification would be so groundbreaking
Standardized ARDS diagnosis with mild/moderate/severe categories based on PaO₂/FiO₂
Improved research consistency, bedside recognition, and severity stratification.
Frequently cited in top-100 ARDS papers and validation studies
What did it change
- Replaced the older 1994 AECC definition (acute, non-cardio-genic pulmonary oedema with severe hypoxemia)
- Improved diagnostic consistency, removed “acute lung injury,” and enabled better severity-based management and research.
- We still use it now!
Newer global definition (2024) recognizes?
- acute, noncardiogenic lung inflammation triggered within one week of a known risk factor
- Also whether intubated / non-intubated / Non-invasive support + whether in resource limited situations.
But
- Only a modest mortality predictor in some cohorts,
- Potential under-recognition in patients on high-flow nasal oxygen or non-invasive ventilation (delaying care)
- Reliance on PEEP ≥5 cmH₂O, may exclude very early/mild cases.
- No large trials “disproved” it, but these gaps prompted the 2024 global definition update.
It’s a keeper!
Paper No. 5
Remember when we used to keep patients topped up to the gills with blood
We thought more of the red would prevent the dead!
No wonder some of the bed spaces looked like a scene from a shark attack!
Along came:
Transfusion Requirements in Critical Care (TRICC Trial) – 1999
Restrictive transfusion strategy was safe and non-inferior (possibly superior), to liberal (Hb <10 g/dL) in critically ill patients!
Landmark in critical care
What did it change
- Shifted transfusion thresholds downward dramatically, moving away from liberal “top-up” policies
- Still in place today restrictive transfusion >7 or >8 amongst special groups where possible harm from anaemia could result (ACS)
A BLOODY GOOD PAPER!….Sorry about that one! Keeper!
Paper No. 6
Remember when we used to try anything to ventilate patients!
We oscillated them to the point their eyeballs almost fell out – We rammed NG tubes down to interrogate the diaphragm
We even over ventilated them to a pH point worse than an energiser battery to ‘paralyse them’ without drugs!
Then there was:
Prone Positioning in Severe Acute Respiratory Distress Syndrome (PROSEVA) – 2013
Who’d have thought lying patients on their fronts, like they were about to undergo some dodgy massage, would be of benefit!
Early prolonged prone positioning (>16 hours/day) reduced 28-day mortality (16% vs 32.8%) and 90-day mortality in severe ARDS, with more ventilator-free days.
What did it change
Definitively practice-changing for severe ARDS.
We used it to it’s max in COVID19
Moved prone positioning from a rare rescue manoeuvre to an early, proactive strategy in severe ARDS.
Fewer cardiac arrests observed.
But
- Underused in some settings; strongly recommended for severe ARDS (PaO₂/FiO₂ <150), with calls for better implementation.
- Increased pressure ulcers/sores (especially facial, chest, and pressure points) compared with supine
- Rare events include endotracheal tube dislodgement or obstruction.
- Harms are manageable with protocols but contributed to implementation barriers;
- No trials disproved the mortality benefit.
PRONE TO KEEP THIS ONE!!
Paper No. 7
Remember when ICU = Chemical Coma using napalm!
Remember when we converted the patients entire circulating volume to propofol. That lipid profile! We were taking the PIS!!…see what I did there…(Propofol Infusion Syndrome)
Then came:
Who’d have thought making patients feel less like a hibernating bear in a zoo would be beneficial!
Spontaneous awakening trials (daily interruption of sedatives) reduced mechanical ventilation duration and ICU length of stay without increasing harm.
What did it change
- Cornerstone of the ABCDE bundle and sedation minimization
- Popularised daily sedation breaks, reducing oversedation, facilitating neurological assessment and weaning.
- Still used – most use protocolised target-based sedation, rather than mandatory full interruptions.
Harm
No significant increase in self-extubation or other adverse events in the trial.
But
- Minor concerns about transient agitation, withdrawal symptoms, or psychological distress in some patients, but these were not consistently higher than continuous sedation
- Underpowered for rare harms; modern practice integrates it safely within bundles.
So…a keeper not a per
Paper No. 8
Remember when we used to tip any old nonsense into our patients?
One of which was Albumin….it is after all human right?!
Then came:
Who’d have thought a colloid could be excuse the pun…SAFE?! Well it was!
No overall mortality difference between 4% albumin and saline in ~7,000 ICU patients
What did it change?
- Shifted practice away from other routine colloid use (with subgroup cautions in sepsis/trauma and signals in traumatic brain injury).
- Core fluid resuscitation classic; underpins all subsequent crystalloid vs colloid debates.
- Largely ended routine albumin use as a first-line resuscitation fluid, favouring crystalloids as a default Albumin is reserved for specific situations
- Large-volume paracentesis
- Cirrhosis and SBP
- Addition after large volume resuscitation with crystalloids in septic shock
- Treatment of hepatorenal syndrome
Harm?
- No mortality difference
- Post-hoc subgroup analysis showed significantly higher 28-day and 2-year mortality with albumin in TBI (increased intracranial pressure from oncotic effects?)
- Recent data say NO to it in burns + ARDS
Keeper…a SAFE
Paper No. 9
Remember when we would literally bang our heads on a wall deciding what was the right thing for volume expansion in shock
We’d plough in the largest molecules faesible, without causing complete clogging of the pipes, cardiac arrest and a GMC referral!
Then came
Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST Trial) – 2012
Who’d have thought something we could sort the shirts of rich victorian people could help our patients?!
No clear mortality difference
HES increased need for renal replacement therapy vs saline with no mortality benefit! We killed the kidneys!
What did it change
- Led to global restrictions on HES use
- Drove colloid safety shifts worldwide.
- Led to rapid decline and regulatory restrictions on synthetic colloids (HES).
Harm
YES!! – Confirmed in 6S trial and JAMA 2013
- AKI rise / RRT use (7.0% vs 5.8%)
- HES withdrawn or contraindicated in most ICU settings due to renal harm signals
- Another re-enforcing the fact that crystalloids dominate fluid resuscitation
20 February 2013, JAMA published a meta-analysis on HES in critically ill patients – If a certain Joachim Boldt’s papers were included in the analysis, there was miraculously no increase in mortality; but if they were excluded, mortality was seen to increase significantly with use of HES!!
Over 200 of his papers have now been withdrawn!! In 2001, the FDA removed HES as a safe colloid for medical usage A safety game changer!
Paper No 10
Remember when opening the tap wasn’t just something you did as part of your washing routine!
The days where a cannula or central line were an invitation to dilute the other rubbish you have poured into the poor patient!
We are ICU! So drowning only happened in unmanned leisure clubs or lifeguardless beaches!
Thank god there was:
Restriction of Intravenous Fluid in ICU Patients with Septic Shock (CLASSIC Trial) – 2022
Who’d have thought dry would fly!
Pee to get free + Trash the swell to get well
Restrictive fluid strategy (after initial resuscitation) was safe
- Reduced total fluid volume
- No increase in 90-day mortality
- No increase in ischemic events in septic shock.
What did it change
- Bolstered fluid stewardships again
- Questions automatic liberal fluids post-initial resuscitation in septic shock
- Adds traction to deresuscitation
Harm
No
- Min adverse events
- No signal of under-resuscitation harm
But
Applicability depends on careful monitoring
You must book the meeting for next year! Critical Care Symposium Manchester 2027
