Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

The results of this multi-centre randomised controlled trial by Hanley et al was published in the Lancet in January 2017.

Background:  Intraventricular lancet-graphic is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome.

Methods:  In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with, NCT00784134.

Findings:  Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar.

Interpretation:  In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status.

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Can high-flow nasal cannula reduce the rate of endotracheal intubation in adult patients with acute respiratory failure compared with conventional oxygen therapy and non-invasive positive pressure ventilation?

This systematic review and meta analysis by Ni et al was published in the January 2017 issue of the journal Chest.

Background:  The effects of high flow nasal cannula (HFNC) on adult patients with acute respiratory failure (ARF) are controversial. We aimed to further determine the effectiveness of HFNC in reducing the rate of endotracheal intubation in adult patients with ARF by comparison to noninvasive positive pressure ventilation (NIPPV) and conventional oxygen therapy (COT).

Methods:  The Pubmed, Embase, Medline, Cochrane Central Register of Controlled Trials (CENTRAL) as well as the Information Sciences Institute (ISI) Web of Science were searched for all the controlled studies that compared HFNC with NIPPV and COT in adult patients having ARF. The primary outcome was the rate of endotracheal intubation and the secondary outcomes were intensive care unit (ICU) mortality and length of ICU stay (ICU LOS).

Results:  Eighteen trials with a total of 3881 patients were pooled in our final studies. Except for ICU mortality (I2=67%, χ2=12.21, P=0.02) and rate of endotracheal intubation (I2=63%, χ2=13.51, P=0.02) between HFNC and NIPPV, no significant heterogeneity was found in outcome measures. Compared with COT, HFNC was associated with a lower rate of endotracheal intubation (Z=2.55, P=0.01), while no significant difference was found in the comparison with NIPPV (Z=1.40, P=0.16). As for the ICU mortality and ICU LOS, HFNC did not show any advantage over either COT or NIPPV.

Conclusions:  In patients with ARF, HFNC is a more reliable alternative of NIPPV to reduce rate of endotracheal intubation than COT.


The full text of the article is available to subscribers to this journal via this link.  The Library and Knowledge Service can obtain the full text of the article for registered members by requesting one via the library website request form.

Effectiveness and safety of procalcitonin evaluation for reducing mortality in adults with sepsis, severe sepsis or septic shock

This systematic review by Andriolo et al was published in the Cochrane Library in January 2017.  The text below is the plain language summary with the full text available via this link.

Review question:  Is procalcitonin evaluation effective in reducing mortality and time receiving antimicrobial therapy in adults with sepsis?cochrane-57-1

Background:  Sepsis is defined as confirmed or suspected infection associated with a systemic inflammatory response syndrome (SIRS). This condition can evolve to an acute organ dysfunction, known as ‘severe sepsis’; or to persistent hypotension, even after adequate fluid replacement, known as ‘septic shock’. Procalcitonin (PCT) is a biological indicator in the blood that has been found to increase during blood infection. We wanted to assess whether evaluation of PCT can reduce mortality and time receiving antimicrobial therapy in adults with blood infection. To this end, we compared PCT versus nothing, versus standard care (only usual clinical judgement) and versus other blood chemical indicators. Nowadays, other chemical indicators include C-reactive protein (CRP), interleukins and neopterin.

Study characteristics:  The evidence is current to July 2015. However, we reran the search in October 2016 and will incorporate the three studies of interest when we update the review. For this version, we included 10 studies in this review. These studies were carried out in Australia, Brazil, China, Czech Republic, France, Germany, Indonesia and Switzerland. Researchers evaluated participants from academic and non-academic surgical, general and trauma intensive care units (ICUs) and emergency departments. All studies analysed adults with confirmed or presumed blood infection. Comparisons were most commonly based on ‘standard care’, but one trial used CRP-guided antibiotic therapy. In six trials, study authors had worked as consultants for, and/or received payments from, companies involved in the procalcitonin analysis.

Key results:  Results showed no significant differences in mortality at longest follow-up (124/573; 21.6% versus 152/583; 26.1%), at 28 days (37/160; 23.1% versus 39/156; 25%), at ICU discharge (28/247; 11.3% versus 25/259; 9.6%) or at hospital discharge (82/398; 20.6% versus 81/407; 19.9%), respectively, for PCT and non-PCT groups. Also, researchers found no differences in mechanical ventilation, clinical severity, reinfection or duration of antimicrobial therapy. No study provided information about participants for whom the antimicrobial regimen was changed from a broad to a narrower spectrum.

Quality of the evidence:  We considered the body of available evidence as having very low to moderate quality owing to absence of methods to prevent errors during studies or absence of information about such methods, as well as possibly insufficient numbers of studies and patients per outcome. Additionally, the authors of most studies worked as consultants and/or received payments from companies involved in the procalcitonin analysis.

What is involved in medicines management across care boundaries?

Phipps, D.L. et al. (2017) BMJ Open. 7:e011765


Objectives: To examine the role of individual and collective cognitive work in managing medicines for acute kidney injury (AKI), this being an example of a clinical scenario that crosses the boundaries of care organisations and specialties.


Conclusions: These themes indicate the critical role of cognitive work on the part of healthcare practitioners, as individuals and as teams, in ensuring effective medicines management during AKI. Our findings suggest that the capabilities underlying this work, for example decision-making, communication and team coordination, should be the focus of training and work design interventions to improve medicines management for AKI or for other conditions.

Read the full article here

Acute liver failure: an up-to-date approach

Cardoso, F.P. et al. Journla of Critical Care. Published online: 19 January 2017
Image source: Spike Walker – Wellcome Images // CC BY-NC-ND 4.0

Image shows light microscopy of liver blood vessels


  • Outcomes of patients with acute liver failure have been improving, but morbidity and mortality are still of concern.
  • Earlier recognition and referral to the intensive care unit have been important to improve these patients’ outcomes.
  • Intensive care management should take into consideration hepatic encephalopathy, cerebral edema and intracranial hypertension, hemodynamics, acute kidney injury, coagulopathy, and infection.
  • Selection of patients for liver transplantation has been based on prognostic scores (e.g. Kings’ College criteria) but limitations may apply.

Read the full abstract here

The management of pulmonary embolism

Lewis, J.E. & Pilcher, D.V. Anaesthesia & Intensive Care Medicine. Published online: 19 January 2017

Pulmonary embolism (PE) is a significant cause of hospitalization, morbidity and mortality and frequently triggers referral to critical care services. Critically ill patients are also at increased risk of developing venous thrombo-embolism (VTE) and acute PE.

Critical care clinicians should be confident in their approach to the patient with suspected and diagnosed PE. Furthermore, the co-morbid conditions in this patient group may present additional challenges both in diagnosis (e.g. safe access to radiology) and management (e.g. absolute and relative contraindications to anticoagulation/thrombolysis in critically ill patients).

This brief review summarizes the contemporary evidence base regarding both diagnosis and treatment strategies and draws upon this to suggest a simple algorithm for investigation, risk stratification and management, particularly tailored to patients within a critical care setting.

Read the abstract here

Albumin administration for fluid resuscitation in burn patients: A systematic review and meta-analysis

This systematic review by Eliajek et al was published in the open access journal Burns.  The full text of this open access article is available to all via this link.

Objective:  The objective was to systematically review the literature summarizing the effect on mortality of albumin compared to non-albumin solutions during the fluid resuscitation phase of burn injured patients.

Data sources:  We searched MEDLINE, EMBASE and CENTRAL and the content of two leading journals in burn care, Burns and Journal of Burn Care and Research.

Study selection:  Two reviewers independently selected randomized controlled trials comparing albumin vs. non-albumin solutions for the acute resuscitation of patients with >20% body surface area involvement.

Data extraction:  Reviewers abstracted data independently and assessed methodological quality of the included trials using predefined criteria.

Data synthesis:  A random effects model was used to assess mortality. We identified 164 trials of which, 4 trials involving 140 patients met our inclusion criteria. Overall, the methodological quality of the included trials was fair. We did not find a significant benefit of albumin solutions as resuscitation fluid on mortality in burn patients (relative risk (RR) 1.6; 95% confidence interval (CI), 0.63–4.08). Total volume of fluid infusion during the phase of resuscitation was lower in patients receiving albumin containing solution −1.00 ml/kg/%TBSA (total body surface area) (95% CI, −1.42 to −0.58).

Conclusion:  The pooled estimate demonstrated a neutral effect on mortality in burn patients resuscitated acutely with albumin solutions. Due to limited evidence and uncertainty, an adequately powered, high quality trial could be required to assess the impact of albumin solutions on mortality in burn patients.