Nurse-led follow-up care for head and neck cancer patients: a quasi-experimental prospective trial

Purpose

The aim of this study was to compare conventional medical follow-up with follow-up containing additional nursing consultations regarding the psychosocial adjustment and health-related quality of life (HRQOL) of head and neck cancer patients.

Methods

Using a quasi-experimental design, patients were enrolled consecutively into two groups. Experimental care covered six 30-min bimonthly nursing follow-up consultations during the first year posttreatment. Data were collected at posttreatment months 1 (baseline), 6, and 12 for both groups.

Results

The intervention group was significantly worse at baseline, based on two of the seven adjustment scales and on the majority of HRQOL scales. However, their outcome at 6 and 12 months was consistent with that of the group which received conventional follow-up. Thus, the intervention group had a larger improvement in scores, and this was significant for one of the seven adjustment scales and 19 of the 33 HRQOL scales at 6 and 12 months, respectively. Most of the differences in HRQOL scales were clinically relevant at 6 months.

Conclusion

These results suggest that nurse-led consultations for patients with head and neck cancer have a positive effect, primarily with respect to HRQOL. Nurse-led follow-up leads to a similar psychosocial adjustment as conventional follow-up, even among patients who showed worse performance at the start of follow-up. Thus, nurse-led follow-up may be a cost-effective way to improve follow-up care for this patient group.     

Vasopressin and copeptin levels in children with sepsis and septic shock

Purpose

Levels of vasopressin and its precursor copeptin in pediatric sepsis and septic shock are not well defined. The main aim of this study is to compare the serum levels of vasopressin and copeptin in children with septic shock or sepsis and in healthy children. We hypothesized that vasopressin and copeptin levels are elevated in early and late stages of pediatric septic shock.

Methods

Three groups were included: healthy children, children with clinical diagnosis of sepsis, and children admitted to the pediatric intensive care unit (PICU) with diagnosis of sepsis shock. Blood samples were drawn from children in all groups within 24 h of admission. For the septic shock group, additional samples at 24-h intervals were drawn up to 120 h after PICU admission. We used competitive immunoassays to determine vasopressin and copeptin levels.

Results

There were 70 children in the control group, 53 children in the sepsis group, and 13 in the septic shock group. At baseline, there was a difference in median vasopressin levels [60.9 (Interquartile range: 32.3, 138.0) vs. 141.1 (45.2, 542) vs. 326 (55.6, 399) pg/mL, p < 0.05], but there was no difference in copeptin levels [1.2 (0.8, 1.8) vs. 1.5 (1.0, 2.2) vs. 0.9 (0.8, 1.2) ng/mL, p = 0.14] between the three groups. There was no difference in vasopressin and copeptin levels in early and late stages of pediatric septic shock.

Conclusions

Baseline vasopressin levels were different between the three groups. In pediatric septic shock, vasopressin and copeptin levels are not robust markers for severity and clinical outcomes.     

Prognostic significance of hypothalamic–pituitary–adrenal axis hormones in early sepsis: a study performed in the emergency department

Purpose

The response of the hypothalamic–pituitary–adrenal (HPA) axis to the sustained stress of sepsis has been the focus of study in recent years because the early phase of sepsis is known to be dominated by major alterations in the HPA axis. This prospective observational study aimed at assessing the predictive values of copeptin and HPA hormones in determining sepsis progression and mortality in the emergency department (ED).

Methods

Serum arginine vasopressin (AVP) and copeptin concentrations were measured upon ED admission. Baseline levels of total and free cortisol and adrenocorticotrophic hormone (ACTH) were measured within 24 h of ED admission. Mortality in Emergency Department Sepsis (MEDS) score was calculated at enrollment.

Results

Our findings demonstrated that serum copeptin, baseline total cortisol, baseline free cortisol and baseline ACTH concentrations gradually increased, based upon the increasing severity of the disease (p < 0.001). Multivariate logistic regression analysis showed that copeptin and total cortisol baseline concentrations were independent predictors of septic shock (odds ratio = 1.034 and 1.355, respectively) and 28-day mortality (odds ratio = 1.039 and 1.499, respectively). The areas under the receiver operating characteristic curve (AUC) for copeptin level in prediction of septic shock was 0.856 and 28-day mortality was 0.826. Importantly, AUC analysis of the combination of copeptin, total cortisol baseline, MEDS score, and procalcitonin level resulted in a more significant prognostic ability than analysis of each parameter alone (p < 0.001).

Conclusions

Increased copeptin and HPA hormones baseline levels may provide crucial information for risk stratification in a variety of septic states in the ED. Furthermore, measurements of copeptin level and serum baseline cortisol concentration are promising independent prognostic markers for mortality in patients with severe sepsis or septic shock.     

Evolution of haemodynamics and outcome of fluid-refractory septic shock in children

Background

Maintaining threshold values of cardiac output (CO) and systemic vascular resistance (SVR) when used as part of the American College of Critical Care Medicine (ACCM) haemodynamic protocol improves the outcomes in paediatric septic shock.

Objective

We observed the evolution of CO and SVR during the intensive care admission of children with fluid-refractory septic shock and report this together with the eventual outcomes.

Design

Prospective observational study.

Setting

Tertiary care Paediatric Intensive Care Unit (PICU) in London.

Methods

Children admitted in fluid refractory septic shock to the Intensive Care Unit over a period of 36 months were studied. Post liver re-transplant children and delayed septic shock admissions were excluded. A non-invasive ultrasound cardiac output monitor device (USCOM) was used to measure serial haemodynamics. Children were allocated at presentation into one of two categories: (1) hospital-acquired infection and (2) community-acquired infection. Vasopressor, inotrope or inodilator therapies were titrated to maintain threshold cardiovascular parameters as per the ACCM guidelines.

Results

Thirty-six children [19 male, mean age (SD) 6.78 (5.86) years] were admitted with fluid-refractory septic shock and studied. At presentation, all 18 children with hospital-acquired (HA) sepsis and 3 from among the community-acquired (CA) sepsis group were in ‘warm shock’ (SVRI < 800 dyne s/cm⁵/m²) whereas 15 of the 18 children with community-acquired sepsis and none in the hospital-acquired group were in ‘cold shock’ [cardiac index (CI) < 3.3 l/min/m²]. All 21 children in ‘warm shock’ were initially commenced on a vasopressor (noradrenaline). Despite an initial good response, four patients developed low CI and needed adrenaline. Similarly, all 15 children in cold shock were initially commenced on adrenaline. However, two of them subsequently required noradrenaline. Five others needed milrinone as an inodilator. In general, both groups of children had normalised SVRI and CI within 42 h of therapy but required variable doses of vasopressors, inotropes or inodilators in a heterogeneous manner. The overall 28-day survival rate was 88.9 % in both groups. Central venous oxygen saturation (ScvO2) was significantly (p = 0.003) lower in the community-acquired group (mean 51.72 % ± 4.26) when compared to the hospital-acquired group (mean 58.72 % ± 1.36) at presentation but showed steady improvement during therapy. Gram-positive organisms were predominant in blood cultures, 61 % in HA and 56 % in CA groups.

Conclusions

In general, we found children with community-acquired septic shock presented in cold shock whereas hospital-acquired septic shock children manifested warm shock. Both types evolved in a heterogeneous manner needing frequent revision of cardiovascular support therapy. However the 28-day survival in both groups was the same at 89 %. Frequent measurements of haemodynamics using non-invasive ultrasound helped in fine tuning cardiovascular therapies.     

Increased MerTK expression in circulating innate immune cells of patients with septic shock

Purpose

A new pathway of three protein tyrosine kinase receptors, namely, the TAM receptor family [Tyro-3, Axl and Mer tyrosine kinase (MerTK)], has recently been described to negatively control immune responses. The objective of this prospective, observational, clinical study was to investigate the expression patterns of TAM receptors in circulating white blood cells collected from patients with septic shock.

Methods

The expression of TAM receptors was measured by flow cytometry in circulating leukocytes from patients with septic shock sampled on days (D) 1–2 (n = 47) and D3–4 (n = 37) after the onset of shock, severe trauma patients at D1–2 after trauma (n = 51) and healthy individuals (n = 23).

Results

On D1–2 after injury, MerTK was overexpressed in monocytes and neutrophils collected from patients with septic shock in comparison with those collected from healthy volunteers and trauma patients. This phenomenon was also observed for mRNA. Conversely, the expression of Tyro-3 and Axl was higher in monocytes from trauma patients versus healthy volunteers or those in septic shock. MerTK expression between D1–2 and D3–4 remained elevated in patients suffering from septic shock who died or developed an intensive care unit-acquired infection, whereas it decreased in patients who recovered uneventfully. This in vivo observed expression pattern was reproduced ex vivo after the incubation of healthy volunteer cells with plasma from septic shock or trauma patients.

Conclusions

MerTK expression in circulating innate immune cells is increased in patients with septic shock in comparison with healthy volunteers and trauma patients. Persistent MerTK overexpression after septic shock is associated with adverse outcome. The role of this family of receptors in the pathophysiology of injury-induced immune dysfunctions deserves to be specifically investigated.     

Inflammatory cytokine measurement quickly discriminates gram-negative from gram-positive bacteremia in pediatric hematology/oncology patients with septic shock

Purpose

We performed a prospective study to evaluate the ability of inflammatory cytokines in discriminating gram-negative from gram-positive bacteremia in septic shock.

Methods

During the study period, the serum inflammatory cytokine levels were measured at the onset of septic shock by flow cytometry in pediatric hematology/oncology patients with septic shock.

Results

One hundred episodes of septic shock were enrolled. Of 97 episodes of monomicrobial infection, 73.2 % were caused by gram-negative bacteremia and 26.8 % by gram-positive bacteremia. Interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α were closely related to the pediatric index of mortality 2 (PIM2) score and mortality. However, although the PIM2 score and mortality were comparable, the IL-6, IL-10, and TNF-α levels were significantly higher in patients with gram-negative bacteremia (GNB) than those with gram-positive bacteremia (median levels, pg/mL: IL-6: 784.1 vs. 254.4, P = 0.001; IL-10: 192.2 vs. 19.7, P < 0.001; TNF-α: 4.2 vs. 2.0, P < 0.001). Of the three cytokines, IL-10 was the most useful biomarker for GNB prediction in the derivation cohort and a cutoff value of 50 pg/mL showed a sensitivity of 70.8 % and a specificity of 80.0 %, with a positive predictive value of 89.5 %. When this cutoff value was applied to the validation cohort, the sensitivity, specificity, and positive predictive value were 80.9, 75.0, and 90.5 %, respectively.

Conclusions

Flow cytometry-based inflammatory cytokine measurement is a helpful adjuvant approach for early and quick discrimination of gram-negative from gram-positive bacteremia in pediatric hematology/oncology patients with septic shock which might be useful for evaluating the severity of shock and the selection and/or timely withdrawal or switch of antibiotics.     

Elevated plasmatic level of soluble IL-7 receptor is associated with increased mortality in septic shock patients

Purpose

Adjunctive immunoadjuvant therapies are now proposed in the treatment of septic patients that develop immune dysfunctions. However, a prerequisite is to identify patients at high risk of death that would benefit from such therapy. Knowing that rhIL-7 is a putative candidate for septic shock treatment, we evaluated the association between increased plasmatic level of soluble CD127 (sCD127, IL-7 receptor alpha chain) and mortality after septic shock.

Methods

sCD127 plasmatic level was measured in 70 septic shock patients sampled at day 1–2 (D1) and day 3–4 (D3) after the onset of shock and 41 healthy volunteers.

Results

Compared with survivors, non-survivors presented with significantly higher sCD127 concentrations at D1 and D3 (p < 0.001 and p = 0.002). At D1, the area under the receiver operating characteristic curve for sCD127 level association with mortality was 0.846 (p < 0.0001). Kaplan–Meier survival curves illustrated that mortality was significantly different after stratification based on D1 sCD127 level (log rank test, hazard ratio 9.10, p < 0.0001). This association was preserved in multivariate logistic regression analysis including clinical confounders (age, SAPS II and SOFA scores, odds ratio 12.71, p = 0.003). Importantly, patient stratification on both D1 sCD127 value and SAPS II score improved this predictive capacity (log rank test, p = 0.0001).

Conclusions

Increased sCD127 plasmatic level enables the identification of a group of septic shock patients at high risk of death. After confirmation in a larger cohort, this biomarker may be of interest for patient stratification in future clinical trials.     

Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality

Purpose

Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis.

Methods

This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F₁₊₂)] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90.

Results

Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F₁₊₂ concentration and with PAI-1 activity and concentration (p < 0.05 for all).

Conclusions

Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.     

Capillary refill time exploration during septic shock

Background

During septic shock management, the evaluation of microvascular perfusion by skin analysis is of interest. We aimed to study the skin capillary refill time (CRT) in a selected septic shock population.

Methods

We conducted a prospective observational study in a tertiary teaching hospital. After a preliminary study to calculate CRT reproducibility, all consecutive patients with septic shock during a 10-month period were included. After initial resuscitation at 6 h (H6), we recorded hemodynamic parameters and analyzed their predictive value on 14-day mortality. CRT was measured on the index finger tip and on the knee area.

Results

CRT was highly reproducible with an excellent inter-rater concordance calculated at 80 % [73–86] for index CRT and 95 % [93–98] for knee CRT. A total of 59 patients were included, SOFA score was 10 [7–14], SAPS II was 61 [50–78] and 14-day mortality rate was 36 %. CRT measured at both sites was significantly higher in non-survivors compared to survivors (respectively 5.6 ± 3.5 vs 2.3 ± 1.8 s, P < 0.0001 for index CRT and 7.6 ± 4.6 vs 2.9 ± 1.7 s, P < 0.0001 for knee CRT). The CRT at H6 was strongly predictive of 14-day mortality as the area under the curve was 84 % [75–94] for the index measurement and was 90 % [83–98] for the knee area. A threshold of index CRT at 2.4 s predicted 14-day outcome with a sensitivity of 82 % (95 % CI [60–95]) and a specificity of 73 % (95 % CI [56–86]). A threshold of knee CRT at 4.9 s predicted 14-day outcome with a sensitivity of 82 % (95 % CI [60–95]) and a specificity of 84 % (95 % CI [68–94]). CRT was significantly related to tissue perfusion parameters such as arterial lactate level and SOFA score. Finally, CRT changes during shock resuscitation were significantly associated with prognosis.

Conclusion

CRT is a clinical reproducible parameter when measured on the index finger tip or the knee area. After initial resuscitation of septic shock, CRT is a strong predictive factor of 14-day mortality.     

The effects of etomidate on adrenal responsiveness and mortality in patients with septic shock

Rationale

Use of etomidate in the critically ill is controversial due to its links with an inadequate response to corticotropin and potential for excess mortality. In a septic shock population, we tested the hypotheses that etomidate administration induces more non-responders to corticotropin and increases mortality and that hydrocortisone treatment decreases mortality in patients receiving etomidate.

Methods

An a-priori sub-study of the CORTICUS multi-centre, randomised, double-blind, placebo-controlled trial of hydrocortisone in septic shock. Use and timing of etomidate administration were collected. Endpoints were corticotropin response and all-cause 28-day mortality in patients receiving etomidate.

Measurements and main results

Five hundred patients were recruited, of whom 499 were analysable; 96 (19.2%) were administered etomidate within the 72 h prior to inclusion. The proportion of non-responders to corticotropin was significantly higher in patients who were given etomidate in the 72 h before trial inclusion than in other patients (61.0 vs. 44.6%, P = 0.004). Etomidate therapy was associated with a higher 28-day mortality in univariate analysis (P = 0.02) and after correction for severity of illness (42.7 vs. 30.5%; P = 0.06 and P = 0.03) in our two multi-variant models. Hydrocortisone administration did not change the mortality of patients receiving etomidate (45 vs. 40%).

Conclusions

The use of bolus dose etomidate in the 72 h before study inclusion is associated with an increased incidence of inadequate response to corticotropin, but is also likely to be associated with an increase in mortality. We recommend clinicians demonstrate extreme caution in the use of etomidate in critically ill patients with septic shock.     

Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study

Purpose

To determine the association between compliance with the Surviving Sepsis Campaign (SSC) performance bundles and mortality.

Design

Compliance with the SSC performance bundles, which are based on the 2004 SSC guidelines, was measured in 29,470 subjects entered into the SSC database from January 1, 2005 through June 30, 2012. Compliance was defined as evidence that all bundle elements were achieved.

Setting

Two hundred eighteen community, academic, and tertiary care hospitals in the United States, South America, and Europe.

Patients

Patients from the emergency department, medical and surgical wards, and ICU who met diagnosis criteria for severe sepsis and septic shock.

Methods

A multifaceted, collaborative change intervention aimed at facilitating adoption of the SSC resuscitation and management bundles was introduced. Compliance with the SSC bundles and associated mortality rate was the primary outcome variable.

Results

Overall lower mortality was observed in high (29.0 %) versus low (38.6 %) resuscitation bundle compliance sites (p < 0.001) and between high (33.4 %) and low (32.3 %) management bundle compliance sites (p = 0.039). Hospital mortality rates dropped 0.7 % per site for every 3 months (quarter) of participation (p < 0.001). Hospital and intensive care unit length of stay decreased 4 % (95 % CI 1–7 %; p = 0.012) for every 10 % increase in site compliance with the resuscitation bundle.

Conclusions

This analysis demonstrates that increased compliance with sepsis performance bundles was associated with a 25 % relative risk reduction in mortality rate. Every 10 % increase in compliance and additional quarter of participation in the SSC initiative was associated with a significant decrease in the odds ratio for hospital mortality. These results demonstrate that performance metrics can drive change in clinical behavior, improve quality of care, and may decrease mortality in patients with severe sepsis and septic shock.     

The effects of vasopressin on acute kidney injury in septic shock

Objective

To compare the effects of vasopressin versus norepinephrine infusion on the outcome of kidney injury in septic shock.

Design and setting

Post-hoc analysis of the multi-center double-blind randomized controlled trial of vasopressin versus norepinephrine in adult patients who had septic shock (VASST).

Patients and intervention

Seven hundred seventy-eight patients were randomized to receive a blinded infusion of either low-dose vasopressin (0.01–0.03 U/min) or norepinephrine infusion (5–15 μg/min) in addition to open-label vasopressors and were included in the outcome analysis. All vasopressors were titrated and weaned to maintain a target blood pressure.

Measurement and results

RIFLE criteria for acute kidney injury were used to compare the effects of vasopressin versus norepinephrine. In view of multiple simultaneous comparisons, a p value of 0.01 was considered statistically significant. Kidney injury was present in 464 patients (59.6%) at study entry. In patients in the RIFLE “Risk” category (n = 106), vasopressin as compared with norepinephrine was associated with a trend to a lower rate of progression to renal “Failure” or “Loss” categories (20.8 vs. 39.6%, respectively, p = 0.03), and a lower rate of use of renal replacement therapy (17.0 vs. 37.7%, p = 0.02). Mortality rates in the “Risk” category patients treated with vasopressin compared to norepinephrine were 30.8 versus 54.7%, p = 0.01, but this did not reach significance in a multiple logistic regression analysis (OR = 0.33, 99% CI 0.10–1.09, p = 0.02). The interaction of treatment group and RIFLE category was significant in predicting mortality.

Conclusions

Vasopressin may reduce progression to renal failure and mortality in patients at risk of kidney injury who have septic shock.     

Evaluating the efficacy of a self-guided Web-based CBT intervention for reducing cancer-distress: a randomised controlled trial

Purpose

This study evaluated the efficacy of a self-guided Web-based cognitive behaviour therapy (CBT) intervention compared to an attention control in improving cancer-related distress, health-related quality of life (HRQOL), and maladaptive coping, among people recently diagnosed with cancer.

Methods

Sixty individuals with cancer diagnosed in the previous 6 months and receiving treatment with curative intent were randomised to receive either the 6-week intervention Cancer Coping Online (CCO: n = 30) or the 6-week Web-based attention control (n = 30). Outcome measures, including cancer distress (the Posttraumatic Stress Scale—Self-Report), general distress (Depression Anxiety Stress Scale), quality of life (EORTC QLQ-C30), and coping (mini-MAC), were administered at baseline, immediately post-intervention, and at 3 and 6 months post-intervention.

Results

Significant main effects for time were found for cancer distress, global QOL, physical function, role function, social function, and anxious preoccupation. Post hoc between-group comparisons showed CCO participants had statistically significantly higher physical functioning compared to controls at 3 months of follow-up (d = ?0.52, p = 0.02). Furthermore, compared to controls, post hoc comparisons found moderate between-group effect sizes favouring CCO post-intervention for cancer distress (d = 0.43) and anxious preoccupation (d = 0.38), and at 6 months of follow-up for global QOL (d = ?0.43).

Conclusions

These results provide preliminary support for the potential efficacy of a self-guided Web-based CBT programme in improving aspects of HRQOL, cancer-related distress, and anxious preoccupation after cancer diagnosis. This paper provides justification for, and will help inform the development of, subsequent larger multi-site studies.

     

Non-pulmonary infections but not specific pathogens are associated with increased risk of AKI in septic shock

Introduction

Little is known regarding the relationship between the anatomic infection site and etiologic pathogen with the occurrence of acute kidney injury (AKI) in severe infections. We set out to determine the association between the site of infection, type of pathogen in septic shock and occurrence of AKI.

Methods

Using a large, international multicenter database that included data from 28 academic and community hospitals, we retrospectively analyzed adult (age >18 years) cases of septic shock occurring between January 1996 and December 2008. Early acute kidney injury (AKI) was classified by the RIFLE criteria at or within 24 h of shock diagnosis. Multivariate logistic regression was used to determine the association between the infection site/microbial pathogen and occurrence of AKI. Analyses were adjusted for demographics, illness severity, comorbidities and intensive care unit interventions (partial adjustment) ± site of infection and microbial pathogen (full adjustment).

Results

After exclusions, 4,493 cases from potentially eligible patients in the database were included in the analytic cohort of whom 3,298 (73.4 %) experienced AKI. Patients with AKI were older (p < 0.0001), had a higher mean Acute Physiology and Chronic Health Evaluation score (p < 0.0001), and had greater laboratory and hemodynamic abnormalities. The most common site of infection among septic shock patients with AKI was the lung (34.5 %), followed by gastrointestinal (GI) (26.2 %) and urinary (15.3 %) sources. Likewise, the most common infecting organism among septic shock patients with AKI was E. coli (23.9 %) followed by S. aureus (GI) (16.1 %) and other enterobacteriaceae (15.7 %). There was a large degree of variability in the occurrence of AKI based on the site of infection and the pathogen in unadjusted analysis (p < 0.0001), which persisted with partial (excluding infection site and microbial pathogen grouping) adjustment (p < 0.0001). Fully adjusted multivariate analysis showed significant variations in AKI only in relation to the anatomic source of infection, with non-pulmonary infections having higher risk than pulmonary infections. The pathogen group/pathogen had no significant independent impact on AKI.

Conclusion

This study demonstrates that the presence of septic AKI varies significantly based on the site of infection but not the type of causative organism.     

Implementation of a multifaceted sepsis education program in an emerging country setting: clinical outcomes and cost-effectiveness in a long-term follow-up study

Purpose

To evaluate whether a multifaceted, centrally coordinated quality improvement program in a network of hospitals can increase compliance with the resuscitation bundle and improve clinical and economic outcomes in an emerging country setting.

Methods

This was a pre- and post-intervention study in ten private hospitals (1,650 beds) in Brazil (from May 2010 to January 2012), enrolling 2,120 patients with severe sepsis or septic shock. The program used a multifaceted approach: screening strategies, multidisciplinary educational sessions, case management, and continuous performance assessment. The network administration and an external consultant provided performance feedback and benchmarking within the network. The primary outcome was compliance with the resuscitation bundle. The secondary outcomes were hospital mortality, hospital and ICU length of stay, quality-adjusted life year (QALY) gain, and cost-effectiveness.

Results

The proportion of patients who received all the required items for the resuscitation bundle improved from 13 % [95 % confidence interval (CI) 8–18 %] at baseline to 62 % (95 % CI 54–69 %) in the last trimester (p < 0.001). Hospital mortality decreased from 55 % (95 % CI 48–62 %) to 26 % (95 % CI 19–32 %, p < 0.001). Full compliance with the resuscitation bundle was associated with lower risk of hospital mortality (propensity weighted corrected risk ratio 0.74; 95 % CI 0.56–0.94, p = 0.02). There was a reduction in the total cost per patient from 29.3 (95 % CI 23.9–35.4) to 17.5 (95 % CI 14.3–21.1) thousand US dollars from baseline to the last 3 months (mean difference ?11,815; 95 % CI ?18,604 to ?5,338). The mean QALY increased from 2.63 (95 % CI 2.15–3.14) to 4.06 (95 % CI 3.58–4.57). For each QALY, the full compliance saves US$5,383.

Conclusions

A multifaceted approach to severe sepsis and septic shock patients in an emerging country setting led to high compliance with the resuscitation bundle. The intervention was cost-effective and associated with a reduction in mortality.     

Control groups in recent septic shock trials: a systematic review

Purpose

The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials.

Methods

We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting.

Results

A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8–32). Of 18 predefined control group characteristics, a mean of 8 (range 2–17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care.

Conclusions

Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.

     

Changes in peroxisome proliferator-activated receptor-gamma activity in children with septic shock

Purpose

To assess changes in peroxisome proliferator-activated receptor-γ (PPARγ) in peripheral blood mononuclear cells (PBMC) from critically ill children with sepsis. Additionally, to investigate the effects of sepsis on the endogenous activator of PPARγ, 15-deoxy-?^12,14-PGJ₂ (15d-PGJ₂), and the downstream targets of PPARγ activity, adiponectin and resistin.

Methods

Single-center, prospective case–control study in critically ill children with systemic inflammatory response syndrome, sepsis or septic shock.

Results

PPARγ nuclear protein expression was decreased but PPARγ activity was increased in PBMC from children with septic shock compared with controls. PPARγ activity on day 1 was significantly higher in patients with higher pediatric risk of mortality (PRISM) score compared with controls [mean 0.22 optical density (OD) ± standard error of the mean (SEM) 0.03 versus 0.12 OD ± 0.02; p < 0.001]. Patients with resolved sepsis had increased levels of the endogenous PPARγ ligand, 15d-PGJ₂, compared with patients with systemic inflammatory response syndrome (SIRS) and septic shock (77.7 ± 21.7 versus 58 ± 16.5 pg/ml; p = 0.03). Plasma high-molecular-weight adiponectin (HMWA) and resistin levels were increased in patients with septic shock on day 1 and were significantly higher in patients with higher PRISM scores. Nonsurvivors from sepsis had higher resistin levels on the first day of hospitalization compared with survivors from septic shock [660 ng/ml, interquartile range (IQR) 585–833 ng/ml versus 143 ng/ml, IQR 66–342 ng/ml; p < 0.05].

Conclusions

Sepsis is associated with altered PPARγ expression and activity in PBMC. Plasma adipokines correlate with risk of mortality scores in sepsis and may be useful biomarkers. Further studies are needed to understand the mechanisms underlying changes in PPARγ in sepsis.     

Early blood lactate area as a prognostic marker in pediatric septic shock

Purpose

We attempted to evaluate whether the early lactate area is useful as an early prognostic marker of mortality in pediatric septic shock patients.

Methods

We performed a retrospective study of pediatric patients with septic shock who were admitted to the pediatric intensive care unit of Asan Medical Center, Seoul, Korea. Serial arterial lactate levels were obtained immediately and then every 6 h after admission for a total of 24 h. The lactate area (mmol/lh) was defined as the sum of the area under the curve (AUC) of serial lactate levels measured during the 24 h following admission. We compared the lactate-associated parameters as a predictor of mortality.

Results

A total of 65 patients were included in this study, and the overall 28-day mortality of these patients was 26.2 %. Survivors compared with non-survivors had an initial lactate level of 3.13 ± 2.79 vs. 6.16 ± 4.87 mmol/l, a lactate clearance of 32.8 ± 63.4 vs. ?30.8 ± 75.6 %, and a lactate area of 59.7 ± 56.0 vs. 168.0 ± 107.0 mmol/lh (p < 0.05 for all variables). Receiver operating characteristic curves indicated a strong predictive power for the lactate area (AUC = 0.828), which demonstrated the largest AUC in comparison with the AUCs of the initial lactate level (0.699) or the 24-h lactate clearance (0.719). Using multivariate logistic regression analysis, the lactate area was a significant prognostic factor.

Conclusion

The early lactate area is a potentially feasible and clinically useful predictor of mortality in pediatric septic shock patients.     

High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial

Purpose

Septic shock is a leading cause of death among critically ill patients, in particular when complicated by acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI.

Methods

This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period.

Results

Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups.

Conclusions

In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.     

Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study

Purpose

The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion. Our objective was to determine the potential benefits of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation.

Methods

We designed a randomized, controlled, double-blind, crossover study comparing the effects of 2.5-h infusion of dobutamine (5 mcg/kg/min fixed-dose) or placebo in 20 septic shock patients with cardiac index ≥2.5 l/min/m² and hyperlactatemia. Primary outcome was sublingual perfused microvascular density.

Results

Despite an increasing cardiac index, heart rate and left ventricular ejection fraction, dobutamine had no effect on sublingual perfused vessel density [9.0 (7.9–10.1) vs. 9.1 n/mm (7.9–9.9); p = 0.24] or microvascular flow index [2.1 (1.8–2.5) vs. 2.1 (1.9–2.5); p = 0.73] compared to placebo. No differences between dobutamine and placebo were found for the lactate levels, mixed venous-arterial pCO₂ gradient, thenar muscle oxygen saturation, capillary refill time or gastric-to-arterial pCO₂ gradient. The indocyanine green plasma disappearance rate [14.4 (9.5–25.6) vs. 18.8 %/min (11.7–24.6); p = 0.03] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [2.1 (1.1–3.1) vs. 2.5 %/s (1.2–3.4); p = 0.01] were worse with dobutamine compared to placebo.

Conclusions

Dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion.