All posts by Stephen Shepherd


A number of injuries can produce a GCS 3 and interventions are multiple with varying evidence of efficacy

Pragmatic, multicentre multinational RCT

Open-label with blinded follow-up

Could be randomised up to 10/7 post injury and must have had first-level interventions to treat it (head up, CSF drainage, etc)

If could not be controlled with hypothermia had barbiturates or hypertonic

Screen 2498 patients, 387 randomised

  • 188 randomised and analysed in hypothermia
  • 187 randomised and analysed in controls

No significant differences in baseline characteristics including age, severity of injury, APACHE, etc AND neurosurgical intervention prior to randomisation

Hypothermia did control ICP more than standard interventions in control group

Stopped early as greater incidence of unfavourable outcome (poor GOSE score) in hypothermia compared with controls

Unadjusted hazard ratio for mortality 1.45 (1.01,2.10) at 6/12

No difference in pneumonia rate between two groups


Conclusion: Titrated hypothermia to reduce raised ICP in addition to standard care did not improve outcomes but and increased mortality

Hypothermia for Intracranial Hypertension after Traumatic Brain Injury


Vasopressin may show benefit in less severe shock in VASS trial

  • ? Weans noradrenaline early
  • ? Dose to low
  • ? Harmful interaction

May reflect beneficial effects on renal function

VASS also suggested that vasopressin + steroids better than noradrenaline + steroids

Questions therefore

  • Should we use earlier?
  • Should we use higher doses?
  • Should we use it with steroids

Factorial 2X2 double blinded RCT < 6/24

  • Vasopressin 0.0-0.06 u/min OR noradrenaline 0-12mch/min
  • When maxed out added either Hydrocort 50mg q6h or placebo

After this, open label catecholamines could be added but would be weaned first

Included adult septic patients, first episode of shock

Exclusions other reasons for steroids, CKD needing RRT

Primary outcome renal failure free days as defined by Stage 3 AKIN

414 randomised, even split

Matched groups

  • Men > women
  • APACHE mean 22
  • 80-90% received noradrenaline pre-randomisation
  • Usually included within 3/24
  • Typical creatinine around 120-130

No difference in haemodynamics between the two groups but noradrenaline group needed more noradrenaline to do so

Fluid requirements and lactate concentrations much this same

Median creatinine level lower in vasopressin patients than noradrenaline

  • No difference in distribution of renal failure
  • No difference in survivors who ever developed renal failure
  • No difference in non-survivors or survivors who did develop renal failure

No difference in mortality. No benefit to adding steroids.

Number of patients who required RRT was significantly lower (ARR 10%) than those who didn’t but once you needed dialysis, duration of that was the same

Conclusion: Early vasopressin maintained BP and reduced noradrenaline requirements as well as reducing the need for RRT but did not reduce the number of renal failure free days


Mortality of immunocompromised patients who need mechanical ventilation has reduced dramatically but remain relatively high (40-60%)

NIV does reduce intubation rates in these patients in older trials (but at that time, mortality for intubation was 80% rather than the lower values found in modern practice)

Multicentre, RCT comparing NIV to O2 on all-cause D28 mortality in immunocompromised patients with hypoxaemic respiratory failure


  • Adult
    • Haematological/solid tumour OR
    • Solid organ transplant OR
    • Long-tern steroids OR
    • Immunosuppression
  • + Respiratory failure

Excluded other organ failures or likely to need ETT / lots of O2

191 received early NIV, 183 O2. No loss to follow-up.

No difference in mortality at 28 days


Didn’t matter what diagnosis was (i.e. solid organ or haematological malignancy). However, was powered for mortality of 35% in oxygen group and was much less than this.

7% of patients only received one session of NIV – either due to need for intubation or poor tolerance (who were in the main subsequently intubated)

No difference in intubation rates, length of ICU stay, 6/12 mortality

1/3 of patients across the two groups received HFNO2 but mortality wasn’t any different

Conclusion: Early NIV did not reduce mortality compared with O2 but study underpowered as mortality much less than was predicted.

Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure


EPO has a long history: EPO-2 EPO-3 may reduce mortality in trauma but concerns about thromboembolic events and efficacy have limited application.

EPO is a pleiotropic cytokine and receptors exist in the blood-brain barrier. In response to hypoxia EPO is produced within the brain. Hence worthy of investigation:

Double-blind, placebo-controlled multi-centre trial

  • GCS < 13
  • Non-penetrating TBI
  • Hb < = normal
  • < 24 h since traumatic injury
  • Valid consent


  • EPO 40 000 IU or placebo SC
    • First dose was administered within 24 h of the estimated time of traumatic brain injury
    • Then weekly for a maximum of three dose
  • Baseline screening USS < = 7 of lower limbs for DVT

Main outcome GOS-E at 6 months

  • GOS-E of 1–4 (death, vegetative state, and severe disability)
  • GOS-E of 5–8 (moderate disability and good recovery)

606 randomised after inclusion / exclusion

Populations well matched

  • Mean age 35
  • Majority male
  • Mainly RTC
  • Most had severe TBI (GCS 3-8)

No effect on proportion with severe disability at 6/12

No increase in thrombotic events (including VTE and MI)

May reduce mortality – 5% ARR at 6/12 but does not achieve statistical significance


Becomes significant after sensitivity testing but this is exploratory

Rates of proximal DVT in TBI 17%

Conclusion: Following moderate or severe traumatic brain injury, erythropoietin did not reduce the number of patients with severe neurological dysfunction (GOS-E level 1–4) or increase the incidence of deep venous thrombosis of the lower limbs. The effect of erythropoietin on mortality remains uncertain.

Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial