Latest Issue of Intensive Care Medicine Volume 42 Number 10


The contents page of this current issue can be accessed via this link.

The articles that are contained in this issue include “Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study” and “Physical declines occurring after hospital discharge in ARDS survivors: a 5-year longitudinal study”.

To access the full text of these articles direct from the journal’s homepage requires a personal subscription.  Individual articles can be ordered via the Rotherham NHS Foundation Trust Library and Knowledge Service.  Registered members of the library can make requests online via this link.

The full text of articles from Intensive Care Medicine from issue older than one year ago is available via this link.  A Rotherham NHS Athens password is required.  Eligible staff can register for one via this link.


Increasing survival after admission to UK critical care units following cardiopulmonary resuscitation

Nolan, J.P. et al. (2016) Critical Care.20(219)

Background: In recent years there have been many developments in post-resuscitation care. We have investigated trends in patient characteristics and outcome following admission to UK critical care units following cardiopulmonary resuscitation (CPR) for the period 2004–2014. Our hypothesis is that there has been a reduction in risk-adjusted mortality during this period.

Methods: We undertook a prospectively defined, retrospective analysis of the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database (CMPD) for the period 1 January 2004 to 31 December 2014. Admissions, mechanically ventilated in the first 24 hours in the critical care unit and admitted following CPR, defined as the delivery of chest compressions in the 24 hours before admission, were identified. Case mix, withdrawal, outcome and activity were described annually for all admissions identified as post-cardiac arrest admissions, and separately for out-of-hospital cardiac arrest and in-hospital cardiac arrest. To assess whether in-hospital mortality had improved over time, hierarchical multivariate logistic regression models were constructed, with in-hospital mortality as the dependent variable, year of admission as the main exposure variable and intensive care unit (ICU) as a random effect. All analyses were repeated using only the data from those ICUs contributing data throughout the study period.

Results: During the period 2004–2014 survivors of cardiac arrest accounted for an increasing proportion of mechanically ventilated admissions to ICUs in the ICNARC CMPD (9.0 % in 2004 increasing to 12.2 % in 2014). Risk-adjusted hospital mortality following admission to ICU after cardiac arrest has decreased significantly during this period (OR 0.96 per year). Over this time, the ICU length of stay and time to treatment withdrawal has increased significantly. Re-analysis including only those 116 ICUs contributing data throughout the study period confirmed all the results of the primary analysis.

Conclusions: Risk-adjusted hospital mortality following admission to ICU after cardiac arrest has decreased significantly during the period 2004–2014. Over the same period the ICU length of stay and time to treatment withdrawal has increased significantly.

Read the full article here

Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials


This article by Jason Roberts et al was published in the American Journal of Respiratory and Critical Care Medicine Volume 194 Issue 6 September 2016.  The full text of the article is available to subscribers via this link.  Registered members of the library can request the full text online via this link

Abstract  Rationale:  Optimization of β-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis.

Objectives:  In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of β-lactam antibiotics.

Methods:  We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of β-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis.

Measurements and Main Results:  We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56–1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03–1.40; P = 0.021), respectively. In a multivariable model, intermittent β-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by non-fermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous β-lactam administration was not independently associated with clinical cure.

Conclusions:  Compared with intermittent dosing, administration of β-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.

Glycemic control, mortality, and hypoglycemia in critically ill patients: a systematic review and network meta-analysis of randomized controlled trials

This research by Yamada et al was published online in Intensive Care Medicine on 16th September 2016.  The full text of the article is available to subscribers via this link.  Registered members of the library can request the full text online via this link

intensive-care-medicinePurpose It is unclear whether tight glycemic control is warranted in all critically ill adults. We employed network meta-analysis to examine the risk of mortality and hypoglycemia associated with different glycemic control targets in critically ill adults.

Methods Electronic databases were searched up to 2016 for randomized controlled trials comparing various insulin regimens in critically ill adults with hyperglycemia. Two reviewers independently extracted information and evaluated quality with the Cochrane risk-of-bias tool. Four glycemic control groups were compared: tight (blood glucose: 4.4 < 6.1 mmol/l), moderate (6.1 < 7.8 mmol/l), mild (7.8 < 10.0 mmol/l), and very mild (10.0 to < 12.2 mmol/l). Network meta-analysis was performed by a frequentist approach with multivariate random effects meta-analysis.

Results Thirty-six randomized trials (17,996 patients) were identified. Compared with very mild control, tight control did not reduce the risk of short-term mortality [relative risk (RR) 0.94 (95 % CI 0.83–1.07, p = 0.36)], and neither did mild control [RR 0.88 (0.73–1.06), p = 0.18] or moderate control [RR 1.1 (0.66–1.84), p = 0.72]. However, severe hypoglycemia (<2.2 mmol/l) was more frequent with tight control than very mild control [RR 5.49 (3.22–9.38), p < 0.001] or mild control [RR 4.47 (2.5–8.03), p < 0.001]. Stratified analyses (cause of death, ICU type, time period, or diabetes) did not find significant between-group differences. Ranking analysis revealed the following hierarchy for avoiding death (highest to lowest rank): mild control, tight control, and very mild control.

Conclusions Network meta-analysis showed no mortality benefit of tight glycemic control in critically ill patients, but fivefold more hypoglycemia versus mild or very mild control.

Take-home message Network meta-analysis showed no mortality benefit of tight glycemic control in critically ill patients, but fivefold more hypoglycemia versus mild or very mild control.

Dexmedetomidine Use in Critically Ill Children With Acute Respiratory Failure

This research by Grant et al was published online in Pediatric Critical Care Medicine in September 2016.  The full text of the article is available to subscribers via this link.  Registered members of the library can request the full text online via this link

Objective: Care of critically ill children includes sedation but current therapies are suboptimal. To describe dexmedetomidine use in children supported on mechanical ventilation for acute respiratory failure.

Design: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial.

Patients and Setting: Data from 2,449 children; 2 weeks to 17 years old in thirty one PICUs.

Interventions: Sedation practices were unrestrained in the usual care arm. Patients were categorized as receiving dexmedetomidine as a primary sedative, secondary sedative, periextubation agent, or never prescribed. Dexmedetomidine exposure and sedation and clinical profiles are described.

Measurements and Main Results: Of 1,224 usual care patients, 596 (49%) received dexmedetomidine. Dexmedetomidine as a primary sedative patients (n = 138; 11%) were less critically ill (Pediatric Risk of Mortality III-12 score median, 6 [interquartile range, 3-11]) and when compared with all other cohorts, experienced more episodic agitation. In the intervention group, time in sedation target improved from 28% to 50% within 1 day of initiating dexmedetomidine as a primary sedative. Dexmedetomidine as a secondary sedative usual care patients (n = 280; 23%) included more children with severe pediatric acute respiratory distress syndrome or organ failure. Dexmedetomidine as a secondary sedative patients experienced more inadequate pain (22% vs 11%) and sedation (31% vs 16%) events. Dexmedetomidine as a periextubation agent patients (n = 178; 15%) were those known to not tolerate an awake, intubated state and experienced a shorter ventilator weaning process (2.1 vs 2.3 d).

Conclusions: Our data support the use of dexmedetomidine as a primary agent in low criticality patients offering the benefit of rapid achievement of targeted sedation levels. Dexmedetomidine as a secondary agent does not appear to add benefit. The use of dexmedetomidine to facilitate extubation in children intolerant of an awake, intubated state may abbreviate ventilator weaning. These data support a broader armamentarium of pediatric critical care sedation.

Plasma transfusions prior to insertion of central lines for people with abnormal coagulation

Thcochrane-57-1is was published in the Cochrane Database of Systematic Reviews in September 2016.  The full text of this review is available via this link

Review question.  We evaluated the evidence about whether people with abnormal coagulation (poor blood clotting) require a plasma transfusion prior to insertion of a central line (central venous catheter (CVC)), and if so, what is the degree of abnormal coagulation at which a plasma transfusion is required.

Background  People with abnormal coagulation often require the insertion of central lines. Central lines are catheters whose tip usually lies in one of two main veins returning blood to the heart. They have a number of uses including: intensive monitoring and treatment of critically-ill patients; giving nutrition into a vein (when the patient cannot eat); giving chemotherapy or other irritant drugs with fewer complications; and when patients require long-term repeated treatments in to a vein. Current practice in many countries is to give plasma transfusions to prevent serious bleeding due to the procedure if blood tests to assess clotting are abnormal. The risk of bleeding after a central line insertion appears to be low if the clinician uses ultrasound to guide insertion of the line. Correction of clotting abnormalities with fresh frozen plasma (FFP) is not without risks of its own, and it is unclear whether this practice is beneficial or harmful. People may be exposed to the risks of a plasma transfusion without any obvious clinical benefit.

Study characteristics  The evidence is current to March 2016. In this review we identified four randomised controlled trials, three trials are still recruiting participants and are due to complete recruitment by February 2018. The completed trial (58 participants) compared plasma transfusion to no plasma transfusion prior to central line insertion.

Key results  There was not enough evidence to determine whether plasma transfusions affected minor or major procedure-related bleeding. The included study did not report the number of people dying due to any cause, the number of people receiving red cell or plasma transfusions, the occurrence of transfusion or line-related complications, length of time in hospital, correction of clotting abnormalities, or quality of life.

Quality of the evidence  The quality of the evidence is very low because this review includes only one small study.

Authors’ conclusions:  There is only very limited evidence from one RCT to inform the decision whether or not to administer prophylactic plasma prior to central venous catheterisation for people with abnormal coagulation. It is not possible from the current RCT evidence to recommend whether or not prophylactic plasma transfusion is beneficial or harmful in this situation. The three ongoing RCTs will not be able to answer this review’s questions, because they are small studies and do not address all of the comparisons included in this review (355 participants in total). To detect an increase in the proportion of participants who had major bleeding from 1 in 100 to 2 in 100 would require a study containing at least 4634 participants (80% power, 5% significance).

Quality Improvement Initiative for Severe Sepsis and Septic Shock Reduces 90-Day Mortality: A 7.5-Year Observational Study

Scheer, S. et al. Critical Care Medicine. Published online: September 22 2016

Objective: To investigate the impact of a quality improvement initiative for severe sepsis and septic shock focused on the resuscitation bundle on 90-day mortality. Furthermore, effects on compliance rates for antiinfective therapy within the recommended 1-hour interval are evaluated.

Design: Prospective observational before-after cohort study.

Setting: Tertiary university hospital in Germany.

Patients: All adult medical and surgical ICU patients with severe sepsis and septic shock.

Intervention: Implementation of a quality improvement program over 7.5 years.

Measurements: The primary endpoint was 90-day mortality. Secondary endpoints included ICU and hospital mortality rates and length of stay, time to broad-spectrum antiinfective therapy, and compliance with resuscitation bundle elements.

Main Results: A total of 14,115 patients were screened. The incidence of severe sepsis and septic shock was 9.7%. Ninety-day mortality decreased from 64.2% to 45.0% (p < 0.001). Hospital length of stay decreased from 44 to 36 days (p < 0.05). Compliance with resuscitation bundle elements was significantly improved. Antibiotic therapy within the first hour after sepsis onset increased from 48.5% to 74.3% (p < 0.001). Multivariate analysis revealed blood cultures before antibiotic therapy (hazard ratio, 0.60-0.84; p < 0.001), adequate calculated antibiotic therapy (hazard ratio, 0.53-0.75; p < 0.001), 1-2 L crystalloids within the first 6 hours (hazard ratio 0.67-0.97; p = 0.025), and greater than or equal to 6 L during the first 24 hours (hazard ratio, 0.64-0.95; p = 0.012) as predictors for improved survival.

Conclusions: The continuous quality improvement initiative focused on the resuscitation bundle was associated with increased compliance and a persistent reduction in 90-day mortality over a 7.5-year period. Based on the observational study design, a causal relationship cannot be proven, and respective limitations need to be considered.

Read the abstract here