Increased incidence of co-infection in critically ill patients with influenza

Background

Co-infection is frequently seen in critically ill patients with influenza, although the exact rate is unknown. We determined the rate of co-infection, the risk factors and the outcomes associated with co-infection in critically ill patients with influenza over a 7-year period in 148 Spanish intensive care units (ICUs).

Methods

This was a prospective, observational, multicentre study. Influenza was diagnosed using the polymerase chain reaction. Co-infection had to be confirmed using standard bacteriological tests. The primary endpoint of this analysis was the presence of community-acquired co-infection, with secondary endpoints including ICU, 28-day and hospital mortality.

Results

Of 2901 ICU patients diagnosed with influenza, 482 (16.6 %) had a co-infection. The proportion of cases of co-infection increased from 11.4 % (110/968) in 2009 to 23.4 % (80/342) in 2015 (P < 0.001). Compared with patients without co-infection, patients with co-infection were older [adjusted odds ratio (aOR) 1.1, 95 % confidence interval 1.1–1.2; P < 0.001] and were more frequently immunosuppressed due to existing HIV infection (aOR 2.6 [1.5–4.5]; P < 0.001) or preceding medication (aOR 1.4 [1.1–1.9]; P = 0.03). Co-infection was an independent risk factor for ICU mortality (aOR 1.4 [1.1–1.8]; P < 0.02), 28-day mortality (aOR 1.3 [1.1–1.7]; P = 0.04) and hospital mortality (aOR 1.9 [1.5–2.5]; P < 0.001).

Conclusions

Co-infection in critically ill patients with influenza has increased in recent years. In this Spanish cohort, age and immunosuppression were risk factors for co-infection, and co-infection was an independent risk factor for ICU, 28-day and hospital mortality.

     

Late-onset moderate to severe acute respiratory distress syndrome is associated with shorter survival and higher mortality: a two-stage association study

Purpose

To evaluate the association between acute respiratory distress syndrome (ARDS) onset time and prognosis.

Methods

Patients with moderate to severe ARDS (N = 876) were randomly assigned into derivation (N = 520) and validation (N = 356) datasets. Both 28-day and 60-day survival times after ARDS onset were analyzed. A data-driven cutoff point between early- and late-onset ARDS was determined on the basis of mortality risk effects of onset times. We estimated the hazard ratio (HR) and odds ratio (OR) of late-onset ARDS using a multivariate Cox proportional hazards model of survival time and a multivariate logistic regression model of mortality rate, respectively.

Results

Late-onset ARDS, defined as onset over 48 h after intensive care unit (ICU) admission (N = 273, 31%), was associated with shorter 28-day survival time: HR = 2.24, 95% CI 1.48–3.39, P = 1.24 × 10^?4 (derivation); HR = 2.16, 95% CI 1.33–3.51, P = 1.95 × 10^?3 (validation); and HR = 2.00, 95% CI 1.47–2.72, P = 1.10 × 10^?5 (combined dataset). Late-onset ARDS was also associated with shorter 60-day survival time: HR = 1.70, 95% CI 1.16–2.48, P = 6.62 × 10^?3 (derivation); HR = 1.78, 95% CI 1.15–2.75, P = 9.80 × 10^?3 (validation); and HR = 1.59, 95% CI 1.20–2.10, P = 1.22 × 10^?3 (combined dataset). Meanwhile, late-onset ARDS was associated with higher 28-day mortality rate (OR = 1.46, 95% CI 1.04–2.06, P = 0.0305) and 60-day mortality rate (OR = 1.44, 95% CI 1.03–2.02, P = 0.0313).

Conclusions

Late-onset moderate to severe ARDS patients had both shorter survival time and higher mortality rate in 28-day and 60-day observations.

     

Prevalence and risk factors related to haloperidol use for delirium in adult intensive care patients: the multinational AID-ICU inception cohort study

Purpose

We assessed the prevalence and variables associated with haloperidol use for delirium in ICU patients and explored any associations of haloperidol use with 90-day mortality.

Methods

All acutely admitted, adult ICU patients were screened during a 2-week inception period. We followed the patient throughout their ICU stay and assessed 90-day mortality. We assessed patients and their variables in the first 24 and 72 h in ICU and studied their association together with that of ICU characteristics with haloperidol use.

Results

We included 1260 patients from 99 ICUs in 13 countries. Delirium occurred in 314/1260 patients [25% (95% confidence interval 23–27)] of whom 145 received haloperidol [46% (41–52)]. Other interventions for delirium were benzodiazepines in 36% (31–42), dexmedetomidine in 21% (17–26), quetiapine in 19% (14–23) and olanzapine in 9% (6–12) of the patients with delirium. In the first 24 h in the ICU, all subtypes of delirium [hyperactive, adjusted odds ratio (aOR) 29.7 (12.9–74.5); mixed 10.0 (5.0–20.2); hypoactive 3.0 (1.2–6.7)] and circulatory support 2.7 (1.7–4.3) were associated with haloperidol use. At 72 h after ICU admission, circulatory support remained associated with subsequent use of haloperidol, aOR 2.6 (1.1–6.9). Haloperidol use within 0–24 h and within 0–72 h of ICU admission was not associated with 90-day mortality [aOR 1.2 (0.5–2.5); p?=?0.66] and [aOR 1.9 (1.0–3.9); p?=?0.07], respectively.

Conclusions

In our study, haloperidol was the main pharmacological agent used for delirium in adult patients regardless of delirium subtype. Benzodiazepines, other anti-psychotics and dexmedetomidine were other frequently used agents. Haloperidol use was not statistically significantly associated with increased 90-day mortality.

     

Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries

Purpose

As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality.

Methods

Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests.

Results

44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10–5.21]; p < 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings.

Conclusions

We did not identify any survival benefit from critical care admission following surgery.

     

The association of duration of boarding in the emergency room and the outcome of patients admitted to the intensive care unit

Background

The demand for critical care beds is increasing out of proportion to bed availability. As a result, some critically ill patients are kept in the Emergency Department (ED boarding) awaiting bed availability. The aim of our study is to examine the impact of boarding in the ED on the outcome of patients admitted to the Intensive Care Unit(ICU).

Methods

This was a retrospective analysis of ICU data collected prospectively at King Abdulaziz Medical City, Riyadh from ED between January 2010 and December 2012 and all patients admitted during this time were evaluated for their duration of boarding. Patients were stratified into three groups according to the duration of boarding from ED. Those admitted less than 6 h were classified as Group I, between 6 and 24 h, Group II and more than 24 h as Group III. We carried out multivariate analysis to examine the independent association of boarding time with the outcome adjusting for variables like age, sex, APACHE, Mechanical ventilation, Creatinine, Platelets, INR.

Results

During the study period, 940 patients were admitted from the ED to ICU, amongst whom 227 (25%) were admitted to ICU within 6 h, 358 (39%) within 6–24 h and 355 (38%) after 24 h. Patients admitted to ICU within 6 h were younger [48.7 ± 22.2(group I) years, 50.6 ± 22.6 (group II), 58.2 ± 20.9 (group III) (P = 0.04)]with less mechanical ventilation duration[5.9 ± 8.9 days (Group I), 6.5 ± 8.1 (Group II) and 10.6 ± 10.5 (Group III), P = 0.04]. There was a significant increase in hospital mortality [51(22.5), 104(29.1), 132(37.2), P = 0.0006) and the ICU length of stay(LOS) [9.55 days (Group I), 9.8 (Group II) and 10.6 (Group III), (P = 0.002)] with increase in boarding duration. In addition, the delay in admission was an independent risk factor for ICU mortality(OR for group III vs group I is 1.90, P = 0.04) and hospital mortality(OR for group III vs Group I is 2.09, P = 0.007).

Conclusion

Boarding in the ED is associated with higher mortality. This data highlights the importance of this phenomenon and suggests the need for urgent measures to reduce boarding and to improve patient flow.

     

Intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (VHYPER)

Purpose

Early noninvasive ventilation (NIV) after extubation decreases the risk of respiratory failure and lowers 90-day mortality in patients with hypercapnia. Patients with chronic respiratory disease are at risk of extubation failure. Therefore, it could be useful to determine the role of NIV with a discontinuous approach, not limited to patients with hypercapnia. We assessed the efficacy of early NIV in decreasing respiratory failure after extubation in patients with chronic respiratory disorders.

Methods

A prospective randomized controlled multicenter study was conducted. We enrolled 144 mechanically ventilated patients with chronic respiratory disorders who tolerated a spontaneous breathing trial. Patients were randomly allocated after extubation to receive either NIV (NIV group, n = 72), performed with a discontinuous approach, for the first 48 h, or conventional oxygen treatment (usual care group, n = 72). The primary endpoint was decreased respiratory failure within 48 h after extubation. Analysis was by intention to treat. This trial was registered with ClinicalTrials.gov (NCT01047852).

Results

Respiratory failure after extubation was less frequent in the NIV group: 6 (8.5%) versus 20 (27.8%); p = 0.0016. Six patients (8.5%) in the NIV group versus 13 (18.1%) in the usual care group were reintubated; p = 0.09. Intensive care unit (ICU) mortality and 90-day mortality did not differ significantly between the two groups (p = 0.28 and p = 0.33, respectively). Median postrandomization ICU length of stay was lower in the usual care group: 3 days (IQR 2–6) versus 4 days (IQR 2–7; p = 0.008). Patients with hypercapnia during a spontaneous breathing trial were at risk of developing postextubation respiratory failure [adjusted odds ratio (95% CI) = 4.56 (1.59–14.00); p = 0.006] and being intubated [adjusted odds ratio (95% CI) = 3.60 (1.07–13.31); p = 0.04].

Conclusions

Early NIV performed following a sequential protocol for the first 48 h after extubation decreased the risk of respiratory failure in patients with chronic respiratory disorders. Reintubation and mortality did not differ between NIV and conventional oxygen therapy.

     

Polymyxin B-immobilized hemoperfusion and mortality in critically ill adult patients with sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis

Purpose

Polymyxin B-immobilized hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that clears circulating endotoxin. Prior trials have shown that PMX-HP improves surrogate endpoints. We aimed to conduct an evidence synthesis to evaluate the efficacy and safety of PMX-HP in critically ill adult patients with sepsis or septic shock.

Methods

We searched for randomized controlled trials (RCTs) in MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, CINAHL, “Igaku Chuo Zasshi”, the National Institute of Health Clinical Trials Register, the World Health Organization International Clinical Trials Registry Platform, the University Hospital Medical Information Network Clinical Trials Registry, the reference lists of retrieved articles, and publications by manufacturers of PMX-HP. The primary outcomes were 28-day all-cause mortality, the number of patients with at least one serious adverse event, and organ dysfunction scores. The GRADE methodology for the certainty of evidence was used.

Results

Six trials (857 participants; weighted mean age 62.5 years) proved eligible. Patient-oriented primary outcomes were assessed. The pooled risk ratio (RR) for 28-day mortality associated with PMX-HP was 1.03 [95% confidence interval (CI) 0.78–1.36; I ² = 25%; n = 797]. The pooled RR for adverse events was 2.17 (95% CI 0.68–6.94; I ² = 0%; n = 717). Organ dysfunction scores over 24–72 h after PMX-HP treatment did not change significantly (standardized mean difference ? 0.26; 95% CI ? 0.64 to 0.12; I ² = 78%; n = 797). The certainty of the body of evidence was judged as low for both benefit and harm using the GRADE methodology.

Conclusions

There is currently insufficient evidence to support the routine use of PMX-HP to treat patients with sepsis or septic shock.

Registration

PROSPERO International Prospective Register of Systematic Reviews (CRD42016038356).

     

Potentially modifiable factors contributing to sepsis-associated encephalopathy

Purpose

Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes.

Methods

We conducted a retrospective analysis of a prospective multicenter database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively.

Results

We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure [adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19–1.67], hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27–5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09–1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53–2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48–3.57), and S. aureus (aOR = 1.54, 95% CI 1.05–2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13–14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09–1.76).

Conclusions

Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.

     

The Concomitant Use of Diuretics,Non-Steroidal Anti-Inflammatory Drugs,and Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers (Triple Whammy), Extreme Heat,and In-Hospital Acute Kidney Injury in Older Medical Patients

Introduction

We investigated whether the concomitant use of diuretics, non-steroidal anti-inflammatory drugs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (triple whammy, TW) predicts in-hospital acute kidney injury (AKI) and whether admission during recorded periods of extreme heat influences this association.

Methods

We retrospectively collected data on patient characteristics and use of TW/non-TW drugs on admission, AKI (increase in serum creatinine ≥ 27 µmol/l either within the first 48 h of admission or throughout hospitalization, primary outcome), length of stay (LOS), and mortality (secondary outcomes) in medical patients ≥65 years admitted (1) during five consecutive heat waves (HWs) between 2007 and 2009 (n = 382) or (2) either before or after each HW, matched for HW period, age, and admission day of the week (non-HW, controls, n = 1339).

Results

Number of TW and non-TW drugs, co-morbidities, number of daily admissions, incidence of in-hospital AKI, LOS, and mortality were similar in the HW and non-HW groups. After adjusting for clinical and demographic confounders, logistic regression showed that TW use did not predict AKI within 48 h of admission either during non-HW periods (OR 0.79, 95% CI 0.34–1.83, P = 0.58) or during HWs (OR 1.02, 95% CI 0.21–2.97, P = 0.97). Similar results were observed when AKI was captured throughout hospitalization. TW use did not predict LOS or mortality irrespective of environmental temperature on admission.

Conclusions

TW use on admission did not predict in-hospital AKI, LOS, or mortality in older medical patients admitted either during periods of normal environmental temperature or during HWs.

     

Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study

Background

In immunocompromised patients with acute hypoxemic respiratory failure (ARF), initial management aims primarily to avoid invasive mechanical ventilation (IMV).

Methods

To assess the impact of initial management on IMV and mortality rates, we performed a multinational observational prospective cohort study in 16 countries (68 centers).

Results

A total of 1611 patients were enrolled (hematological malignancies 51.9%, solid tumors 35.2%, systemic diseases 17.3%, and solid organ transplantation 8.8%). The main ARF etiologies were bacterial (29.5%), viral (15.4%), and fungal infections (14.7%), or undetermined (13.2%). On admission, 915 (56.8%) patients were not intubated. They received standard oxygen (N = 496, 53.9%), high-flow oxygen (HFNC, N = 187, 20.3%), noninvasive ventilation (NIV, N = 153, 17.2%), and NIV + HFNC (N = 79, 8.6%). Factors associated with IMV included age (hazard ratio = 0.92/year, 95% CI 0.86–0.99), day-1 SOFA (1.09/point, 1.06–1.13), day-1 PaO₂/FiO₂ (1.47, 1.05–2.07), ARF etiology (Pneumocystis jirovecii pneumonia (2.11, 1.42–3.14), invasive pulmonary aspergillosis (1.85, 1.21–2.85), and undetermined cause (1.46, 1.09–1.98). After propensity score matching, HFNC, but not NIV, had an effect on IMV rate (HR = 0.77, 95% CI 0.59–1.00, p = 0.05). ICU, hospital, and day-90 mortality rates were 32.4, 44.1, and 56.4%, respectively. Factors independently associated with hospital mortality included age (odds ratio = 1.18/year, 1.09–1.27), direct admission to the ICU (0.69, 0.54–0.87), day-1 SOFA excluding respiratory score (1.12/point, 1.08–1.16), PaO₂/FiO₂ < 100 (1.60, 1.03–2.48), and undetermined ARF etiology (1.43, 1.04–1.97). Initial oxygenation strategy did not affect mortality; however, IMV was associated with mortality, the odds ratio depending on IMV conditions: NIV + HFNC failure (2.31, 1.09–4.91), first-line IMV (2.55, 1.94–3.29), NIV failure (3.65, 2.05–6.53), standard oxygen failure (4.16, 2.91–5.93), and HFNC failure (5.54, 3.27–9.38).

Conclusion

HFNC has an effect on intubation but not on mortality rates. Failure to identify ARF etiology is associated with higher rates of both intubation and mortality. This suggests that in addition to selecting the appropriate oxygenation device, clinicians should strive to identify the etiology of ARF.

     

Evaluation of [<Superscript>18</Superscript>F]CP18 as a Substrate-Based Apoptosis Imaging Agent for the Assessment of Early Treatment Response in Oncology

Purpose

The substrate-based positron emission tomography (PET) tracer [¹⁸F]CP18 is capable of detecting the activity of caspase-3/7, two key executioner proteases in the apoptosis pathway, through selective cleavage of the ligand by the activated proteases and subsequent accumulation in apoptotic cells. Using an in vitro and in vivo model of colorectal cancer (CRC), we investigated whether [¹⁸F]CP18 tracer accumulation provides a measure for apoptosis and reliably reflects early treatment response to chemotherapeutics.

Procedures

[¹⁸F]CP18 cell uptake was assessed in treated Colo205 cells (saline, 5-fluorouracil (5-FU), irinotecan or their combination) and correlated with caspase-3/7 activity. [¹⁸F]CP18 imaging was performed in Colo205 xenografts, starting with a baseline μPET/micro X-ray computed tomography (?μCT) scan, followed by a 3-day treatment with saline (n = 5), 5-FU (low sensitivity, n = 4), irinotecan (high sensitivity, n = 5), or a combination of both (n = 7). The study was concluded with a second [¹⁸F]CP18 scan, 24 h after final treatment administration, followed by tumor removal for gamma counting (%ID/g) and for cleaved caspase-3 immunohistochemistry (apoptotic index/necrosis). Tumors were delineated on μCT images and, using the obtained volumes of interest, average percentage injected dose per cubic centimeter (%ID/cm³) was calculated from every μPET image.

Results

In vitro, [¹⁸F]CP18 cell uptake was positively correlated with caspase-3/7 activity (r = 0.59, p = 0.003). A drug-dependent increase in [¹⁸F]CP18 tumor uptake compared to baseline was observed in animals treated with 5-FU (+14 ± 25 %), irinotecan (+56 ± 54 %), and their combination (+158 ± 69 %, p = 0.002). %ID/cm³ showed a positive relationship with both %ID/g (r = 0.83, p < 0.0001) and the apoptotic index (r = 0.60, p = 0.004), but not with tumor necrosis (r = 0.22, p = 0.36).

Conclusion

Both our in vitro and in vivo findings have shown the ability of [¹⁸F]CP18-PET to visualize therapy-induced cancer cell apoptosis and possibly serve as a biomarker for early therapy response.

     

Impact of the driving pressure on mortality in obese and non-obese ARDS patients: a retrospective study of 362 cases

Purpose

The relation between driving pressure (plateau pressure-positive end-expiratory pressure) and mortality has never been studied in obese ARDS patients. The main objective of this study was to evaluate the relationship between 90-day mortality and driving pressure in an ARDS population ventilated in the intensive care unit (ICU) according to obesity status.

Methods

We conducted a retrospective single-center study of prospectively collected data of all ARDS patients admitted consecutively to a mixed medical-surgical adult ICU from January 2009 to May 2017. Plateau pressure, compliance of the respiratory system (Crs) and driving pressure of the respiratory system within 24 h of ARDS diagnosis were compared between survivors and non-survivors at day 90 and between obese (body mass index?≥?30 kg/m²) and non-obese patients. Cox proportional hazard modeling was used for mortality at day 90.

Results

Three hundred sixty-two ARDS patients were included, 262 (72%) non-obese and 100 (28%) obese patients. Mortality rate at day 90 was respectively 47% (95% CI, 40–53) in the non-obese and 46% (95% CI, 36–56) in the obese patients. Driving pressure at day 1 in the non-obese patients was significantly lower in survivors at day 90 (11.9?±?4.2 cmH₂O) than in non-survivors (15.2?±?5.2 cmH₂O, p?<?0.001). Contrarily, in obese patients, driving pressure at day 1 was not significantly different between survivors (13.7?±?4.5 cmH₂O) and non-survivors (13.2?±?5.1 cmH₂O, p?=?0.41) at day 90. After three multivariate Cox analyses, plateau pressure [HR?=?1.04 (95% CI 1.01–1.07) for each point of increase], Crs [HR?=?0.97 (95% CI 0.96–0.99) for each point of increase] and driving pressure [HR?=?1.07 (95% CI 1.04–1.10) for each point of increase], respectively, were independently associated with 90-day mortality in non-obese patients, but not in obese patients.

Conclusions

Contrary to non-obese ARDS patients, driving pressure was not associated with mortality in obese ARDS patients.

     

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition

Purpose

Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS_CRF?) in comparison with others (ARDS_CRF+).

Methods

Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.

Results

The prevalence of ARDS_CRF? was 7.5 % (95 % CI [5.5–9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS_CRF? patients had a lower logistic organ dysfunction score (4 [3–8] vs. 10 [6–13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46–74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02–4.18]; p = 0.044). Among ARDS_CRF? patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03–0.62]) was associated with ICU survival.

Conclusions

The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

     

Effect of a condolence letter on grief symptoms among relatives of patients who died in the ICU: a randomized clinical trial

Purpose

Family members of patients who die in the intensive care unit (ICU) may experience symptoms of stress, anxiety, depression, posttraumatic stress disorder (PTSD), and/or prolonged grief. We evaluated whether grief symptoms were alleviated if the physician and the nurse in charge at the time of death sent the closest relative a handwritten condolence letter.

Methods

Multicenter randomized trial conducted among 242 relatives of patients who died at 22 ICUs in France between December 2014 and October 2015. Relatives were randomly assigned to receiving (n = 123) or not receiving (n = 119) a condolence letter. The primary endpoint was the Hospital Anxiety and Depression Score (HADS) at 1 month. Secondary endpoints included HADS, complicated grief (ICG), and PTSD-related symptoms (IES-R) at 6 months. Observers were blinded to group allocation.

Results

At 1 month, 208 (85.9%) relatives completed the HADS; median score was 16 [IQR, 10–22] with and 14 [8–21.5] without the letter (P = 0.36). Although scores were higher in the intervention group, there were no significant differences regarding the HADS-depression subscale (8 [4–12] vs. 6 [2–12], mean difference 1.1 [?0.5 to 2.6]; P = 0.09) and prevalence of depression symptoms (56.0 vs. 42.4%, RR 0.76 [0.57–1.00]; P = 0.05). At 6 months, 190 (78.5%) relatives were interviewed. The intervention significantly increased the HADS (13 [7–19] vs. 10 [4–17.5], P = 0.04), HADS-depression subscale (6 [2–10] vs. 3 [1–9], P = 0.02), prevalence of depression symptoms (36.6 vs. 24.7%, P = 0.05) and PTSD-related symptoms (52.4 vs. 37.1%, P = 0.03).

Conclusions

In relatives of patients who died in the ICU, a condolence letter failed to alleviate grief symptoms and may have worsened depression and PTSD-related symptoms. Trial registration Clinicaltrials.gov Identifier: NCT02325297.

     

Effect of a multifaceted educational intervention for anti-infectious measures on sepsis mortality: a cluster randomized trial

Purpose

Guidelines recommend administering antibiotics within 1 h of sepsis recognition but this recommendation remains untested by randomized trials. This trial was set up to investigate whether survival is improved by reducing the time before initiation of antimicrobial therapy by means of a multifaceted intervention in compliance with guideline recommendations.

Methods

The MEDUSA study, a prospective multicenter cluster-randomized trial, was conducted from July 2011 to July 2013 in 40 German hospitals. Hospitals were randomly allocated to receive conventional continuous medical education (CME) measures (control group) or multifaceted interventions including local quality improvement teams, educational outreach, audit, feedback, and reminders. We included 4183 patients with severe sepsis or septic shock in an intention-to-treat analysis comparing the multifaceted intervention (n = 2596) with conventional CME (n = 1587). The primary outcome was 28-day mortality.

Results

The 28-day mortality was 35.1% (883 of 2596 patients) in the intervention group and 26.7% (403 of 1587 patients; p = 0.01) in the control group. The intervention was not a risk factor for mortality, since this difference was present from the beginning of the study and remained unaffected by the intervention. Median time to antimicrobial therapy was 1.5 h (interquartile range 0.1–4.9 h) in the intervention group and 2.0 h (0.4–5.9 h; p = 0.41) in the control group. The risk of death increased by 2% per hour delay of antimicrobial therapy and 1% per hour delay of source control, independent of group assignment.

Conclusions

Delay in antimicrobial therapy and source control was associated with increased mortality but the multifaceted approach was unable to change time to antimicrobial therapy in this setting and did not affect survival.

     

Impact of chronic liver disease in intensive care unit acquired pneumonia: a prospective study

Purpose

To assess the impact of chronic liver disease (CLD) on ICU-acquired pneumonia.

Methods

This was a prospective, observational study of the characteristics, microbiology, and outcomes of 343 consecutive patients with ICU-acquired pneumonia clustered according to the presence of CLD.

Results

Sixty-seven (20 %) patients had CLD (67 % had liver cirrhosis, LC), MELD score 26 ± 9, 20 % Child–Pugh class C). They presented higher severity scores than patients without CLD both on admission to the ICU (APACHE II, LC 19 ± 6 vs. other CLD 18 ± 6 vs. no CLD 16 ± 6; p < 0.001; SOFA, 10 ± 3 vs. 8 ± 4 vs. 7 ± 3; p < 0.001) and at onset of pneumonia (APACHE II, 19 ± 6 vs. 17 ± 6 vs. 16 ± 5; p = 0.001; SOFA, 11 ± 4 vs. 9 ± 4 vs. 7 ± 3; p < 0.001). Levels of CRP were lower in patients with LC than in the other two groups (day 1, 6.5 [2.5–11.5] vs. 13 [6–23] vs. 15.5 [8–24], p < 0.001, day 3, 6 [3–12] vs. 16 [9–21] vs. 11 [5–20], p = 0.001); all the other biomarkers were higher in LC and other CLD patients. LC patients had higher 28- and 90-day mortality (63 vs. 28 %, p < 0.001; 72 vs. 38 %, p < 0.001, respectively) than non-CLD patients. Presence of LC was independently associated with decreased 28- and 90-day survival (95 % confidence interval [CI], 1.982–17.250; p = 0.001; 95 % confidence interval [CI], 2.915–20.699, p = 0.001, respectively).

Conclusions

In critically ill patients with ICU-acquired pneumonia, CLD is associated with a more severe clinical presentation and poor clinical outcomes. Moreover, LC is independently associated with 28- and 90-day mortality. The results of this study are important for future trials focused on mortality.     

Polymyxin B hemoperfusion in endotoxemic septic shock patients without extreme endotoxemia: a post hoc analysis of the EUPHRATES trial

Purpose

The EUPHRATES trial examined the impact of polymyxin B hemoperfusion (PMX) on mortality in patients with septic shock and endotoxemia, defined as EAA?≥?0.60. No difference was found in 28-day all-cause mortality. However, the trial showed that in some patients with septic shock the burden of endotoxin activity was extreme (EAA?≥?0.9). In a post hoc analysis, we evaluated the impact of PMX use in patients with septic shock and endotoxin activity measured between 0.6–0.89.

Methods

Post-hoc analysis of the EUPHRATES trial for the 194 patients with EAA?≥?0.6–0.89 who completed two treatments (PMX or sham). The primary end point was mortality at 28 days adjusted for APACHE II score and baseline mean arterial pressure (MAP). Additional end points included changes in MAP, cumulative vasopressor index (CVI), median EAA reduction, ventilator-free days (VFD), dialysis-free days (DFD) and hospital length of stay. Subpopulations analyzed were site and type of infection and those with norepinephrine dose > 0.1 mcg/kg/min at baseline.

Results

At 28 days, 23 patients of 88 (26.1%) in the PMX group died versus 39 of 106 (36.8%) in the sham group [risk difference 10.7%, OR 0.52, 95% CI (0.27, 0.99), P?=?0.047]. When unadjusted for baseline variables, P?=?0.11. The 28-day survival time in the PMX group was longer than for the sham group [HR 0.56 (95% CI 0.33, 0.95) P?=?0.03]. PMX treatment compared with sham showed greater change in MAP [median (IQR) 8 mmHg (??0.5, 19.5) vs. 4 mmHg (??4.0, 11) P?=?0.04] and VFD [median (IQR) 20 days (0.5, 23.5) vs. 6 days (0, 20), P?=?0.004]. There were no significant differences in other end points. There was a significant difference in mortality in PMX-treated patients with no bacterial growth on culture [PMX, 6/30 (20%) vs. sham, 13/31 (41.9%), P?=?0.005]. The median EAA change in the population was ??12.9% (range: increase 49.2%–reduction 86.3%). The mortality in the above median EAA change group was PMX: 6/38 (15.7%) vs. sham 15/49 (30.6%), P?=?0.08.

Conclusions

These hypothesis-generating results, based on an exploratory post hoc analysis of the EUPHRATES trial, suggest measurable responses in patients with septic shock and an EAA?≥?0.6 to 0.89 on changes in mean arterial pressure, ventilator-free days and mortality.

Trial registration

Clinicaltrials.gov Identifier: NCT01046669. Funding Spectral Medical Incorporated.

     

LiFe: a liver injury score to predict outcome in critically ill patients

Purpose

To develop a liver function-related risk prediction tool to identify acute-on-chronic liver failure patients at greatest risk of in-hospital mortality.

Methods

The LiFe (liver, injury, failure, evaluation) score, was constructed based on the opinions of 157 intensivists within the European Society for Intensive Care Medicine. Experts were surveyed and instructed to weigh the diagnostic importance of each feature of a proposed prediction model. We performed a retrospective cohort study of 1916 patients with chronic liver disease admitted to a medical or surgical ICU between 1997, and 2011 in three large hospitals in Boston, USA, and London, UK, with arterial lactate, total bilirubin and INR drawn at ICU admission. The derivation cohort consisted of ICU patients from Brigham and Women’s Hospital and Massachusetts General Hospital in Boston (n = 945), and the validation cohort comprised patients from Kings College Hospital, London, admitted to the Liver Intensive Therapy Unit (n = 971). A clinical prediction model was derived and validated based on a logistic regression model describing the risk of in-hospital mortality as a function of the predictors (arterial lactate 0–1.9, ≥2.0–3.9, ≥4.0–5.9, ≥6.0 mg/dL; total bilirubin 0–1.9, ≥2.0–3.9, ≥4.0–5.9, ≥6.0 mg/dL; INR 0–1.9, ≥2.0–3.9, ≥4.0–5.9, ≥6.0) at ICU admission. Performance analysis of the LiFe score against SOFA, CLIF-SOFA, APACHE II and SAPS II was completed in the validation cohort of critically ill cirrhotic patients.

Results

The derivation cohort (n = 941) was 53 % male with a mean age of 65 years and an in-hospital mortality rate of 30 %. The validation cohort (n = 971) was 63 % male with mean age of 51 years and an in-hospital mortality rate of 52 %. The C statistic for the prediction model was 0.74 (95 % CI 0.70–0.77) in the derivation cohort and 0.77 (95 % CI 0.74–0.80) in the validation cohort. In the validation cohort, in-hospital mortality was 17 % in the low-risk group (0 risk score points), 28 % in the intermediate-risk group (1–3 points), 47 % in the high-risk group (4–8 points), and 77 % in the very high-risk group (>8 points). In the validation cohort, the C statistics for SOFA, CLIF-SOFA, APACHE II, and SAPS II were 0.80, 0.81, 0.77, and 0.78, respectively. Further, a significant positive correlation exists between LiFe score and acute-on-chronic liver failure grade, (r = 0.478, P < 0.001).

Conclusions

Our LiFe score calculated from arterial lactate, total bilirubin and INR at ICU admission is a simple, quick and easily understandable score that may increase clinical utility for risk prediction in ICU patients with acute-on-chronic liver failure. The LiFe score can be used in place of physiological based scores for early risk prediction in patients with chronic liver disease but is not intended to replace CLIF-SOFA as a benchmark for prognostication.

     

Prognostic value of chromogranin A in severe sepsis: data from the FINNSEPSIS study

Purpose

To assess the prognostic information of chromogranin A (CgA), a marker associated with adrenergic tone and myocardial function, in patients with severe sepsis.

Methods

CgA levels were measured at the time of study inclusion and 72 h later in 232 patients with severe sepsis recruited from 24 ICUs in Finland (FINNSEPSIS study).

Results

Sixty-five patients (28 %) died during the index hospitalization. CgA levels at inclusion and after 72 h correlated with several established indices of risk in sepsis. Patients who died during the hospitalization had higher baseline CgA levels than hospital survivors: 14.0 (Q1–3, 7.4–27.4) versus 9.1 (5.9–15.8) nmol/l, P = 0.002, and after 72 h: 16.2 (9.0–31.1) versus 9.8 (6.0–18.0) nmol/l, P = 0.001. Prior cardiovascular disease (P = 0.04) and cardiovascular SOFA levels on day 3 (P = 0.03) were associated with higher CgA levels after 72 h by linear regression. CgA levels on study inclusion and after 72 h were independently associated with hospital mortality by logistic regression: OR (logarithmically transformed CgA levels) 1.95 (95 % CI 1.01–3.77), P = 0.046 and OR 2.03 (95 % CI 1.18–3.49), P = 0.01, respectively. The prognostic accuracy was comparable for CgA measurements and SAPS II score, and the addition of CgA measurements to the SAPS II score improved risk stratification of the patients as assessed by the category-free net reclassification index. A CgA level >6.6 nmol/l on study inclusion was associated with septic shock during the hospitalization.

Conclusion

CgA levels measured during hospitalization for severe sepsis are associated with cardiovascular dysfunction and may provide additional prognostic information in patients with severe sepsis.

     

Effect of available intravenous access on accuracy and timeliness of epinephrine administration

Purpose

To evaluate the effect of available intravenous (IV) access on the accuracy and timeliness of epinephrine administration during a surprise mock severe contrast reaction.

Methods

Informed consent was waived for this prospective randomized IRB-approved study. Radiology trainees with previous annual hands-on contrast reaction training (n = 46) were randomized to one of two surprise mock contrast reactions over a 23-month period: Group 1—severe laryngeal edema with IV access present (n = 27) or Group 2—severe laryngeal edema without IV access present (n = 19). Both intramuscular (IM, Epi-Pen^®) and IV epinephrine were available in both scenarios. Time-to-treat and epinephrine administration error rates were compared by study group and by route of administration using two-tailed Student’s t test or χ ² test. Epinephrine administration errors were correlated with training experience using Pearson’s correlation.

Results

Mean time to epinephrine administration was significantly faster for scenarios without IV access (Group 2: 35 ± 16 s vs. Group 1: 62 ± 49 s, p = 0.03), and for intramuscular administrations overall (IM: 42 ± 34 s vs. IV: 98 ± 46 s, p < 0.001). Epinephrine administration errors were common: (63% [17/27, Group 1] vs. 61% [11/18, Group 2], p = 1.00), had no relationship with time to most recent hands-on training (r = 0.24, p = 0.11), and were not predicted by year of post-graduate training (r = 0.04, p = 0.79).

Conclusions

Lack of IV access is associated with a faster epinephrine administration time but no improvement in epinephrine administration error rate among radiology trainees responding to a surprise mock severe contrast reaction. Annual hands-on training appears to have little effect on epinephrine administration accuracy.