Previous Studies

In this section we describe how trials have informed the critical care evidence base.

We also show how previous studies conducted by ACET in King's Critical Care have improved our evidence base. It is vital that the results of studies are fed back to critical care staff and that they are established in our practice.

It is vital that when critical care studies are completed that we know that the study included patients from our ICU and our community. This also helps highlight why we want to enroll patients on our ICUs into NIHR studies.

What we now know from trials...

It is safe to target lower blood pressure to target a MAP of 65 in general critical illness
Goal-directed therapy based on central venous saturation monitoring has no benefit over standard care when treating patients with septic shock
Starch-based colloids are harmful when compared to crystalloids. They are more expensive; increase the risk of death and are associated with specfic hazards such as coagulopathy, and anaphylaxis.
Restrictive transfusion targets convey improved outcomes when compared to liberal transfusion practice.
FRESH blood does not improve outcomes when compared with older stored blood.
Goal-directed therapy targeting supranormal oxygen delivery (DO2) may improve outcome from major trauma but not in patients with septic shock. Increasing DO2 (with fluids, blood and inotropes) may increase mortality in patients with septic shock.
Monitoring such as pulmonary artery catheter placement may not lead to better outcomes.
Stress-dose hydrocortisone conveys a benefit to patients with septic shock and specifically reduces pressor requirements
Short-acting beta blockers do not improve pathophysiology in the resuscitation of patients who have septic shock and may be harmful
The sequence order of different vasopressors such as noradrenaline and vasopressin does not matter in relation to outcomes of septic shock
Levosimendan does not improve the outcome of patients with septic shock and may provoke adverse effects eg arrhythmia (ie no advantage from supporting myocardial depression from sepsis)
There are no significant differences when comparing parenteral with enteral nutrition (infection rates or outcomes are the same)
Therapeutic hypothermia is potentially harmful in patients with traumatic brain injury- although it reduces raised intracranial pressure it worsens long-term outcome
Early decompressive craniectomy may reduce ICP but lead to worse longer term neurological outcomes
High dose methylprednisolone does not improve outcome in cerebral odema related to major trauma
Tranexamic acid given in patients with closed head injury reduces mortality in trauma patients
Daily consideration of sedation holds and spontaneous breathing trials reduces length of stay and mortality
Dexmedetomidine may produce better outcomes if used as the hypnotic sedative in older patients (>65) but may be harmful in younger patients
Tight glycaemic control conveys no benefit to the general ICU patient population
Artificial haemoglobin-based resuscitation fluid does not convey outcome benefit to patients presenting with traumatic haemorrhagic shock
Beta-lactam antibiotics are better given by infusion
Statins provide a beneficial outcome in COVID 19 and also in the pro-inflammatory phenotype of ARDS
Step-wise recruitment ladders in ARDS should be used with caution and may lead to lung injury
Early mobilisation of ICU patients does not lead to better outcomes including mortality, reduced length of stay
NAVA is a stable form of spntaneous ventilatory support and can be compared with pressure support in a trial setting. It is plausable that NAVA may shorten time on a ventilator when compared with pressure support.

Trials we have previously done in King's Critical Care

A2B. This trial has yet to report, but compared the clinical and health economic benefit of different hypnotic sedatives (Propofol vs Dexmedetomidine vs Clonidine)

SPICE 3. This compared Propofol with Dexmedetomidine and showed relative benefit for older patients from Dexmedetomidine. SPICE 4 trial is now planned targeting patients in the older age group.

BLING 3. This trial compared bolus versus infusion of beta lactam antibiotics (specifically Pip-Tazobactam or Meropenem)

PHIND. This trial examined the efficacy of a near patient device that was able to phenotype ARDS into pro-inflammatory versus non-inflammatory phenotype

RECOVERY. This was a platform trial deployed during the COVID 19 pandemic that examined the efficacy of treatments for CoV SARS2

CORTICUS. This trial compared low dose hydrocortisone with standard care in patients with septic shock.

65. This was an ICNARC sponsored study that looked at clinical outcomes of patients targeting a MAP of 65 versus standard care

PROMISE. This trial looked at the effectiveness of goal-directed therapy in septic shock (the UK equivalent of ARISE and PRoCESS). All three trials found no difference in goal-directed therapy using a central venous saturation monitor versus standard care.

ABC. This was a transfusion trigger study that compared liberal vs restrictive transfusion targets and showed that

ASTOP. This was a trial that examined markers of fungal sepsis and examined the pathogeneis of candidaemia in patients at risk.

TEST-IT. This trial looked at

AspiFlu. This trial looked at the incidence of Aspergillus in patients with influenza and other types of viral pneumonitis (including COVID 19)

CRYOSTAT 2. This trial investigated the effect of giving cryoglobulin to major trauma patients who presented in haemorrhagic shock.

COSBID. This trial was a study looking at the incidence and clinical associations of spreading depolarisations, a pathophysiological response to traumatic brain injury.

CENTER TBI. We participated in this epidemiological study that ran across Europe and looked at the population characteristics

CRASH 3. This examined the efficacy of tranexamic acid on closed head injury and showed that patient outcomes were improved.

NOSTRA. This looked at a nitric oxide synthase inhibitor in brain injury.

OPTIC ICP. This looked at a surrogate measurement of raised intracranial pressure using optic nerve ultrasound.

MODET. An epidemiological study that looked at multiorgan failure in elderly patients with major trauma.

FRAIL-T. An epidemiological study that looked at outcomes after major trauma in older patients.

EUROTHERM3235. This study showed that using hypothermia to treat raised intracranial pressure in patients with traumatic brain injury worsened their outcome. It was another reminder that treating numbers alone (in this case ICP) will not necessarily improve outcome.

HALT-IT. This examined the clinical effectiveness of tranexaminc acid in upper GI bleeding. King's Critical Care withdrew from this study due to persistent lack of equipoise-clinicians at KCH believed that tranexamic acid is effective treatment

MOSAICC. This is an ongoing study. King's Critical Care withdrew from this study as we do not admit patients who fulfill the inclusion criteria-in other

POEM. This study developed and validated a simple scoring system to grade the severity

MICROSHOCK. This study looked at the relationship between the microcirculation and critical illness outcome in patients with septic shock.

MICRORESUS. This study looked at the use of microcirculatory monitoring in the management of shocked critically-ill patients.

MICROSHOCK Renal. This looked at ultrasound assessment of renal perfusion in conjunction with microcirculatory assessment.

PHARLAP. This looked at the clinical effectiveness of staircase recruitment manoevers in ARDS. The trail was stopped early because of potential for patient harm from the intervention.

VANISH. This looked at the clinical effect of the sequence of pressor use in septic shock (using vasopressin and noradrenaline).

STRESS-L. This study looked at the ultra-short acting betablocker, Landiolol to test clinical effectiveness in the treatment of septic shock. It was stopped early due to lack of efficacy and a potential signal for harm.

VACIRISS. This looked at the clinical efficacy of the pneumococcal vaccine as an immunomodulator in patients who survived septic shock to see if it can prevent further episodes of severe sepsis.

TEAM. This trial compared early mobilisation of intensive care patients compared to standard care. It showed there was no benefit from early mobilisation.

RESTUS. This trial was a randomised RCT looking at the feasibility of comparing Neurally-adjusted ventilatory assist (NAVA) with pressure support ventilation. It showed that deploying the NAVA intervention was possible with signls for clinical benefit from the NAVA ventilation mode.

EFFORT. This trial looked at the clinical efficacy of adding high protein feed in patients with critical illness compared to standard care.

IVC. This study compard patient outcomes after intermittent vs continuous feeding

CALORIES. This study compared enteral nutrition vs parentral nutrition. It showed no difference, and specifically showed that PN is not associated with increased infection.

MoSAICC. This study looked at comparing use of bicarbonate vs usual care in patients admitted with metabolic acidosis related to renal failure. We found this difficult to recruit to since we either admit for renal replacement, or the patient did not meet inclusion criteria. So it seems likely we did not have equipoise, or our casemix meant that we tended to use renal replacement earlier.

STAART-AKI. This study looked at timing of renal replacement. Similar to MOSAICC we found this a challenging study to recruit to.