Early goal-directed resuscitation of patients with septic shock: current evidence and future directions

Early goal-directed resuscitation of patients with septic shock: current evidence and future directions
Critical Care 2015, 19:286  doi:10.1186/s13054-015-1011-9

Gupta, R, et al

Severe sepsis and septic shock are among the leading causes of mortality in the intensive care unit. Over a decade ago, early goal-directed therapy (EGDT) emerged as a novel approach for reducing sepsis mortality and was incorporated into guidelines published by the international Surviving Sepsis Campaign. In addition to requiring early detection of sepsis and prompt initiation of antibiotics, the EGDT protocol requires invasive patient monitoring to guide resuscitation with intravenous fluids, vasopressors, red cell transfusions, and inotropes. The effect of these measures on patient outcomes, however, remains controversial. Recently, three large randomized trials were undertaken to re-examine the effect of EGDT on morbidity and mortality: the ProCESS trial in the United States, the ARISE trial in Australia and New Zealand, and the ProMISe trial in England. These trials showed that EGDT did not significantly decrease mortality in patients with septic shock compared with usual care. In particular, whereas early administration of antibiotics appeared to increase survival, tailoring resuscitation to static measurements of central venous pressure and central venous oxygen saturation did not confer survival benefit to most patients. In the following review, we examine these findings as well as other evidence from recent randomized trials of goal-directed resuscitation. We also discuss future areas of research and emerging paradigms in sepsis trials.

Postoperative Critical Care of the Adult Cardiac Surgical Patient: Part II: Procedure-Specific Considerations, Management of Complications, and Quality Improvement

Postoperative Critical Care of the Adult Cardiac Surgical Patient: Part II:Procedure-Specific Considerations, Management of Complications, and Quality Improvement

Critical Care Medicine: September 2015 - Volume 43 - Issue 9 - p 1995–2014

Stephens S, et al


Objectives: The armamentarium of cardiac surgery continues to expand, and the cardiac intensivist must be familiar with a broad spectrum of procedures and their specific management concerns. In the conclusion of this two-part review, we will review procedure-specific concerns after cardiac surgery and the management of common complications. We also discuss performance improvement and outcome assurance. 
Data Source and Synthesis: Narrative review of relative English language peer-reviewed medical literature. 
Conclusions: Knowledge of procedure-specific sequelae informs anticipation and prevention of many complications after cardiac surgery. Most complications after cardiac surgery fall into a limited number of categories. Familiarity with common complications combined with a structured approach to management facilitates response to even the most complicated postoperative situations. Standardized care and constant self-examination are essential for programmatic improvement and consistent high-quality care.

Ventilator-Associated Events: Prevalence, Outcome, and Relationship With Ventilator-Associated Pneumonia

Ventilator-AssociatedEvents: Prevalence, Outcome, and Relationship With Ventilator-Associated Pneumonia
Critical Care Medicine: September 2015 - Volume 43 - Issue 9 - p 1798–1806

Bouadma, L, et al

Objectives: Centers for Disease Control and Prevention built up new surveillance paradigms for the patients on mechanical ventilation and the ventilator-associated events, comprising ventilator-associated conditions and infection-related ventilator-associated complications. We assess 1) the current epidemiology of ventilator-associated event, 2) the relationship between ventilator-associated event and ventilator-associated pneumonia, and 3) the impact of ventilator-associated event on antimicrobials consumption and mechanical ventilation duration. 

Design: Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1996-2012). Patients: Patients on mechanical ventilation for greater than or equal to 5 consecutive days were classified as to the presence of a ventilator-associated event episode, using slightly modified Centers for Disease Control and Prevention definitions. Intervention: None. 

Measurements and Main Results: Among the 3,028 patients, 2,331 patients (77%) had at least one ventilator-associated condition, and 869 patients (29%) had one infection-related ventilator-associated complication episode. Multiple causes, or the lack of identified cause, were frequent. The leading causes associated with ventilator-associated condition and infection-related ventilator-associated complication were nosocomial infections (27.3% and 43.8%), including ventilator-associated pneumonia (14.5% and 27.6%). Sensitivity and specificity of diagnosing ventilator-associated pneumonia were 0.92 and 0.28 for ventilator-associated condition and 0.67 and 0.75 for infection-related ventilator-associated complication, respectively. A good correlation was observed between ventilator-associated condition and infection-related ventilator-associated complication episodes, and ventilator-associated pneumonia occurrence: R2 = 0.69 and 0.82 (p < 0.0001). The median number of days alive without antibiotics and mechanical ventilation at day 28 was significantly higher in patients without any ventilator-associated event (p < 0.05). Ventilator-associated condition and infection-related ventilator-associated complication rates were closely correlated with antibiotic use within each ICU: R2 = 0.987 and 0.99, respectively (p < 0.0001). 

Conclusions: Ventilator-associated event is very common in a population at risk and more importantly highly related to antimicrobial consumption and may serve as surrogate quality indicator for improvement programs.

Clinical management for patients admitted to a critical care unit with severe sepsis or septic shock

Clinical management for patients admitted to a critical care unit with severe sepsis or septic shock
Article in press: Accepted: April 24, 2015; Published Online: August 17, 2015

Cheung W et al,

The Surviving Sepsis Campaign promotes the use of norepinephrine as the first-line inotropic support for patients presenting with severe sepsis or septic shock in cases of persistent hypotension, despite adequate fluid resuscitation. However, there is little published evidence on how much noradrenaline is administered to such patients when admitted to the intensive care unit (ICU). The authors report the clinical management of this group of patients, with a special focus on the total amount and duration of norepinephrine infusion required.

Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis

Enteral glutamine supplementation in critically ill patients: a systematic review and meta-analysis
Critical Care 2015, 19:294

van Zanten A, et al


Introduction: Glutamine (GLN) has been suggested to have a beneficial influence on outcomes of critically ill patients. However, recent large-scale trials have suggested harm associated with GLN supplementation. Recently, systematic reviews on the use of parenteral GLN have been published; however, less information is available on the role of enteral GLN. Therefore, the aim of this systematic review was to study the effects of enteral GLN supplementation in patients with critical illness. 
Methods: We identified randomized controlled trials conducted from 1980 to 2014 with enterally administered GLN in adult critically ill patients. Studies of parenteral GLN only or combined enteral-parenteral GLN were excluded. The methodological quality of studies was scored, and trial data were statistically combined. We examined a priori the treatment effects in subgroups of trials of burn and trauma patients. 
Results: A total of 11 studies involving 1079 adult critically ill patients and enteral GLN supplementation were identified. Enteral GLN supplementation was not associated with a reduction of hospital mortality (risk ratio [RR] 0.94, 95 % confidence interval [CI] 0.65–1.36; p =0.74), infectious complications (RR 0.93, 95 % CI 0.79–1.10; p =0.39) or stay in the intensive care unit (weighted mean difference [WMD] −1.36 days, 95 % CI −5.51 to 2.78; p =0.52). However, there was a significant reduction in hospital stay (WMD 4.73 days, 95 % CI −8.53 to −0.90; p =0.02). In the subset of studies of patients with burns, enteral GLN supplementation was associated with significant reductions in hospital mortality (RR 0.19, 95 % 0.06–0.67; p =0.010) and hospital stay (WMD −9.16, 95 % CI −15.06 to −3.26; p =0.002). There was no effect in trauma patients. 
Conclusions: Enteral GLN supplementation does not confer significant clinical benefit in critically ill patients, with the exception of reduced hospital stay. There may be a significant benefit in patients with burns, but data are sparse and larger randomized trials are warranted to confirm this effect.

Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis

Venous thromboembolism in the ICU: main characteristics, diagnosis and thromboprophylaxis
Critical Care 2015, 19:287  doi:10.1186/s13054-015-1003-9

Minet C et al,


Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep venous thrombosis (DVT), is a common and severe complication of critical illness. Although well documented in the general population, the prevalence of PE is less known in the ICU, where it is more difficult to diagnose and to treat. Critically ill patients are at high risk of VTE because they combine both general risk factors together with specific ICU risk factors of VTE, like sedation, immobilization, vasopressors or central venous catheter. Compression ultrasonography and computed tomography (CT) scan are the primary tools to diagnose DVT and PE, respectively, in the ICU. CT scan, as well as transesophageal echography, are good for evaluating the severity of PE. Thromboprophylaxis is needed in all ICU patients, mainly with low molecular weight heparin, such as fragmine, which can be used even in cases of non-severe renal failure. Mechanical thromboprophylaxis has to be used if anticoagulation is not possible. Nevertheless, VTE can occur despite well-conducted thromboprophylaxis.

The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock: A Systematic Review and Meta-Analysis

The Impact of Timing of Antibiotics on Outcomes in Severe Sepsis and Septic Shock:A Systematic Review and Meta-Analysis
Critical Care Medicine: September 2015 - Volume 43 - Issue 9 - p 1907–1915

Sterling S, et al

Objectives: We sought to systematically review and meta-analyze the available data on the association between timing of antibiotic administration and mortality in severe sepsis and septic shock. Data Sources: A comprehensive search criteria was performed using a predefined protocol. Study Selection: Inclusion criteria: adult patients with severe sepsis or septic shock, reported time to antibiotic administration in relation to emergency department triage and/or shock recognition, and mortality. Exclusion criteria: immunosuppressed populations, review article, editorial, or nonhuman studies. Data Extraction: Two reviewers screened abstracts with a third reviewer arbitrating. The effect of time to antibiotic administration on mortality was based on current guideline recommendations: 1) administration within 3 hours of emergency department triage and 2) administration within 1 hour of severe sepsis/septic shock recognition. Odds ratios were calculated using a random effect model. The primary outcome was mortality. Data Synthesis: A total of 1,123 publications were identified and 11 were included in the analysis. Among the 11 included studies, 16,178 patients were evaluable for antibiotic administration from emergency department triage. Patients who received antibiotics more than 3 hours after emergency department triage (< 3 hr reference) had a pooled odds ratio for mortality of 1.16 (0.92–1.46; p = 0.21). A total of 11,017 patients were evaluable for antibiotic administration from severe sepsis/septic shock recognition. Patients who received antibiotics more than 1 hour after severe sepsis/shock recognition (< 1 hr reference) had a pooled odds ratio for mortality of 1.46 (0.89–2.40; p = 0.13). There was no increased mortality in the pooled odds ratios for each hourly delay from less than 1 to more than 5 hours in antibiotic administration from severe sepsis/shock recognition. Conclusion: Using the available pooled data, we found no significant mortality benefit of administering antibiotics within 3 hours of emergency department triage or within 1 hour of shock recognition in severe sepsis and septic shock. These results suggest that currently recommended timing metrics as measures of quality of care are not supported by the available evidence.

Bench-to-bedside review: the effects of hyperoxia during critical illness

Bench-to-bedside review: the effects of hyperoxia during critical illness
Critical Care 2015, 19:284  doi:10.1186/s13054-015-0996-4

Helmerhorst H, et al

Oxygen administration is uniformly used in emergency and intensive care medicine and has life-saving potential in critical conditions. However, excessive oxygenation also has deleterious properties in various pathophysiological processes and consequently both clinical and translational studies investigating hyperoxia during critical illness have gained increasing interest. Reactive oxygen species are notorious by-products of hyperoxia and play a pivotal role in cell signaling pathways. The effects are diverse, but when the homeostatic balance is disturbed, reactive oxygen species typically conserve a vicious cycle of tissue injury, characterized by cell damage, cell death, and inflammation. The most prominent symptoms in the abundantly exposed lungs include tracheobronchitis, pulmonary edema, and respiratory failure. In addition, absorptive atelectasis results as a physiological phenomenon with increasing levels of inspiratory oxygen. Hyperoxia-induced vasoconstriction can be beneficial during vasodilatory shock, but hemodynamic changes may also impose risk when organ perfusion is impaired. In this context, oxygen may be recognized as a multifaceted agent, a modifiable risk factor, and a feasible target for intervention. Although most clinical outcomes are still under extensive investigation, careful titration of oxygen supply is warranted in order to secure adequate tissue oxygenation while preventing hyperoxic harm.

The Future of Sepsis Performance Improvement

The Future of Sepsis Performance Improvement

Critical Care Medicine:September 2015 - Volume 43 - Issue 9 - p 1787–1789
doi: 10.1097/CCM.0000000000001231

Dellinger, R. Phillip

The Surviving Sepsis Campaign (SSC) announced a goal of decreasing mortality by 25% when it released The Barcelona Declaration in October 2002 (1). The publication of the first International Guidelines for the Management of Severe Sepsis and Septic Shock in 2004 began a sustained effort to reduce sepsis mortality, which subsequently included collaboration with the Institute for Healthcare Improvement to develop “care bundles” as a means of implementing a core group of recommendations....

A trajectory towards partnership in care – Patient experiences of autonomy in intensive care: A qualitative study

A trajectory towards partnership in care – Patient experiences of autonomy in intensive care: A qualitative study

Article in press. Accepted: April 8, 2015; Published Online: August 13, 2015 Accepted: April 8, 2015; Published Online: August 13, 2015
Lindberg C, et al


The aim of this study was to describe and elucidate patient experiences of autonomy in an intensive care context from a caring perspective.

Physician report cards and rankings yield long-lasting hand hygiene compliance exceeding 90 %

Physician report cards and rankings yield long-lasting hand hygiene compliance exceeding 90 %

Critical Care 2015, 19:292  doi:10.1186/s13054-015-1008-4

Reich J, et al


Hand hygiene is an effective, low-cost intervention that prevents the spread of multidrug-resistant bacteria. Despite mandatory education and reminders, compliance by physicians in our hospital remained stubbornly low. Our objective was to study whether surveillance by our unit coordinator (secretary) paired with regular feedback to chiefs of service would increase physician hand hygiene compliance in the ICU.
Method: The ICU unit coordinator was trained to observe and measure hand hygiene compliance. Data were collected on hand hygiene compliance at room entry and exit for 9 months. Percentage compliance for each medical and surgical subspecialty was reported to chiefs of service at the end of each month. Comparative rankings by service were widely distributed throughout the physician organization and the medical center. 
Results: The hand hygiene compliance rate among physicians increased from 65.1 % to 91.6 % during the study period..................

Bioelectrical impedance vector analysis in critically ill patients: a prospective, clinician-blinded investigation

Bioelectrical impedance vector analysis in critically ill patients: a prospective,clinician-blinded investigation

Critical Care 2015, 19:290  doi:10.1186/s13054-015-1009-3
Jones S, et al

Assessment of fluid status in critically ill patients is challenging. We aimed to assess the feasibility and validity of bioelectrical impedance vector analysis (BIVA) as a measure of hydration in critically ill patients. 

Methods: We performed twice-daily BIVA measurements and fluid balance calculations and recorded physiological variables in mechanically ventilated patients within 24 h of intensive care unit (ICU) admission for up to 5 days. Treating clinicians were blinded to BIVA results. 

Results: We performed 344 BIVA measurements in 61 patients. According to BIVA, 14 patients (23 %) were dehydrated, 22 (36 %) were normally hydrated and 25 (41 %) were overhydrated upon ICU admission. Patients with normal BIVA hydration were less sick, had fewer comorbidities and had less deranged physiology than patients found to be dehydrated or overhydrated with BIVA. Cumulative fluid balance increased in patients found to be dehydrated with BIVA by a mean of 3.4±2.2 L, whereas in patients found to be overhydrated with BIVA, it decreased by a mean of 4.5±6.9 L. In patients found to be normally hydrated with BIVA, fluid balance remained unchanged. BIVA-defined hydration increased with 1 L (median change 1.5 %, P =0.09) or 2 L (median change 0.7 %, P =0.09) of calculated fluid gains. BIVA-defined hydration decreased (median change −0.8 %, P =0.02) with a negative cumulative fluid balance of >2 L. BIVA-defined hydration between first and last measurement correlated with the corresponding change in fluid balance (ρ =0.25, P =0.05). 

Conclusions: BIVA is feasible in critically ill patients. Its validity is supported by the observed characteristics of patients with different degrees of BIVA hydration upon admission and by different fluid management of such patients by blinded clinicians. The sensitivity of repeated BIVA hydration measurements to detect fluid accumulation or fluid balance changes ...

Does Appropriate Antibiotic Therapy Mean Only Adequate Spectrum and Timing?

Does Appropriate Antibiotic Therapy Mean Only Adequate Spectrum and Timing?
August 2015 - Volume 43 - Issue 8 - p 1773–1774

Lipman, J et al

Editorial placing some of the pharmokinetic responses of critically ill patients in context.

Clinical review: intensive care unit acquired weakness

Clinical review: intensive care unit acquired weakness

Critical Care 2015, 19:274  doi:10.1186/s13054-015-0993-7

Hermans G, Van den Berghe G

A substantial number of patients admitted to the ICU because of an acute illness, complicated surgery, severe trauma, or burn injury will develop a de novo form of muscle weakness during the ICU stay that is referred to as “intensive care unit acquired weakness” (ICUAW). This ICUAW evoked by critical illness can be due to axonal neuropathy, primary myopathy, or both. Underlying pathophysiological mechanisms comprise microvascular, electrical, metabolic, and bioenergetic alterations, interacting in a complex way and culminating in loss of muscle strength and/or muscle atrophy. ICUAW is typically symmetrical and affects predominantly proximal limb muscles and respiratory muscles, whereas facial and ocular muscles are often spared. The main risk factors for ICUAW include high severity of illness upon admission, sepsis, multiple organ failure, prolonged immobilization, and hyperglycemia, and also older patients have a higher risk. The role of corticosteroids and neuromuscular blocking agents remains unclear. ICUAW is diagnosed in awake and cooperative patients by bedside manual testing of muscle strength and the severity is scored by the Medical Research Council sum score. In cases of atypical clinical presentation or evolution, additional electrophysiological testing may be required for differential diagnosis. The cornerstones of prevention are aggressive treatment of sepsis, early mobilization, preventing hyperglycemia with insulin, and avoiding the use parenteral nutrition during the first week of critical illness. Weak patients clearly have worse acute outcomes and consume more healthcare resources. Recovery usually occurs within weeks or months, although it may be incomplete with weakness persisting up to 2 years after ICU discharge. Prognosis appears compromised when the cause of ICUAW involves critical illness polyneuropathy, whereas isolated critical illness myopathy may have a better prognosis. In addition, ICUAW has shown to contribute to the risk of 1-year mortality. Future research should focus on new preventive and/or therapeutic strategies for this detrimental complication of critical illness and on clarifying how ICUAW contributes to poor longer-term prognosis.