Nutrition support during extracorporeal membrane oxygenation (ECMO) in adults: a retrospective audit of 86 patients

Purpose

Extracorporeal membrane oxygenation (ECMO) is increasingly being used to support critically ill patients with severe cardiac and/or respiratory failure. It has been claimed that the resulting haemodynamic alterations, particularly in venoarterial ECMO, mean that enteral feeding is unsafe and/or poorly tolerated. This study aims to investigate this question and to identify any barriers to optimal nutrition.

Methods

Data were retrospectively collected for 86 patients who received ECMO between January 2007 and July 2012 in a tertiary critical care unit/ECMO referral centre. All were fed using existing protocols that emphasise early enteral feeding in preference over parenteral or delayed enteral nutrition.

Results

Thirty-one patients required ECMO for cardiac failure, and all of these received venoarterial ECMO; the remainder received venovenous ECMO. Enteral feeds started for all patients at average 13.1 h [standard deviation (SD) 16.7 h] after ICU admission, reaching goal rate on day 2.6 (SD 1.4). Thirty-three patients experienced significant feeding intolerance during the first 5 days, but of these 20 were managed effectively with prokinetic medications; 18 required parenteral nutrition to supplement inadequately tolerated tube feeds. Intolerance did not differ between ECMO modes. Overall patients tolerated 79.7 % of goal nutrition each day in the first 2 weeks.

Conclusions

Enteral feeding can be well tolerated by patients who are receiving ECMO, whether in venovenous or venoarterial mode. ECMO should not exclude patients from receiving the well-documented benefits of early enteral feeding in critical illness.     

Long-term mortality in patients with chronic obstructive pulmonary disease following extracorporeal membrane oxygenation for cardiac assist after cardiovascular surgery

Purpose

Information on predisposing risk factors influencing long-term survival after extracorporeal membrane oxygenation (ECMO) support remains scarce. In critically ill patients chronic obstructive pulmonary disease (COPD) is an independent risk factor for mortality and morbidity. We assessed the influence of COPD on cardiovascular and all-cause mortality in patients undergoing ECMO therapy.

Methods

We prospectively included 191 patients undergoing veno-arterial ECMO therapy following cardiovascular surgery at a university-affiliated tertiary care center into our registry.

Results

The median follow-up time was 51 months (IQR 34–71 months) corresponding to 4,197 overall months of follow-up. A total of 125 patients (65 %) died; 88 % of deaths were due to cardiovascular causes. Long-term survival was decreased in patients with COPD after 1 year (23 % vs. 44 %) and after 6 years (14 % vs. 35 %) compared to patients without COPD. COPD was independently associated with all-cause mortality with a hazard ratio of 4.22 (95 % CI 1.04–17.11, p = 0.04) and cardiovascular mortality with a hazard ratio of 5.87 (95 % CI 1.41–24.47, p = 0.02).

Conclusions

We identified COPD as a strong and independent predictor of long-term all-cause mortality and cardiovascular mortality in patients undergoing ECMO therapy following cardiovascular surgery. The current study presents valuable information for a comprehensive decision-making process prior to ECMO implantation and helps to identify high-risk patients that may benefit from intensified treatment of co-morbidities and close check-ups after hospital discharge.     

Hormonal status and ICU-acquired paresis in critically ill patients

Background

The pathogenesis of intensive care unit-acquired paresis (ICUAP), a frequent and severe complication of critical illness, is poorly understood. Since ICUAP has been associated with female gender in some studies, we hypothesized that hormonal dysfunction might contribute to ICUAP.

Objective

To determine the relationship between hormonal status, ICUAP and mortality in patients with protracted critical illness.

Design

Prospective observational study.

Setting

Four medical and surgical ICUs.

Patients

ICU patients mechanically ventilated for >7 days.

Interventions

None.

Measurements and main results

Plasma levels of insulin growth factor-1 (IgF1), prolactin, thyroid stimulating hormone (TSH), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS) and cortisol were measured on the first day patients were awake (day 1). Mean blood glucose from admission to day 1 was calculated. ICUAP was defined as Medical Research Council sum score <48/60 on day 7.

Results

We studied 102 patients (65 men and 37 women, 29 post-menopausal), of whom 24 (24%) died during hospitalization. Among the 86 patients tested at day 7, 39 (49%) had ICUAP, which was more frequent in women (63% versus men 36%, p = 0.02). Mean blood glucose was higher in patients with ICUAP. Estradiol/testosterone ratio was greater in men with ICUAP.

Conclusion

ICUAP 7 days after awakening was associated with increased blood glucose and with biological evidence of hypogonadism in men, while an association with hormonal dysfunction was not detected in women.     

Outcome of acute respiratory distress syndrome patients treated with extracorporeal membrane oxygenation and brought to a referral center

Purpose

Patients with severe acute respiratory distress syndrome (ARDS) are candidates for extracorporeal membrane oxygenation (ECMO) therapy. The evaluation of organ severity is difficult in patients considered for cannulation in a distant hospital. This study was designed to identify early factors associated with hospital mortality in ARDS patients treated with ECMO and retrieved from referring hospitals.

Methods

Data from 85 consecutive ARDS patients equipped with ECMO by our mobile team and consequently admitted to our ICU were prospectively collected and analyzed.

Results

The main ARDS etiologies were community-acquired bacterial pneumonia (35 %), influenza pneumonia (23 %) (with 12 patients having been treated during the first half of the study period), and nosocomial pneumonia (14 %). The median (interquartile range) time between contact from the referring hospital and patient cannulation was 3 (1–4) h. ECMO was venovenous in 77 (91 %) patients. No complications occurred during transport by our mobile unit. Forty-eight patients died at the hospital (56 %). Based on a multivariate logistic regression, a score including age, SOFA score, and a diagnosis of influenza pneumonia was constructed. The probability of hospital mortality following ECMO initiation was 40 % in the 0–2 score class (n = 58) and 93 % in the 3–4 score class (n = 27). Patients with an influenza pneumonia diagnosis and a SOFA score before ECMO of less than 12 had a mortality rate of 22 %.

Conclusions

Age, SOFA score, and a diagnosis of influenza may be used to accurately evaluate the risk of death in ARDS patients considered for retrieval under ECMO from distant hospitals.     

Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study

Purpose

To compare characteristics, clinical evolution and outcome in adult patients with influenza A (H1N1) acute respiratory distress syndrome (ARDS) treated with or without extracorporeal membrane oxygenation (ECMO).

Methods

A prospective observational study of patients treated in Marseille South Hospital from October 2009 to January 2010 for confirmed influenza A (H1N1)-related ARDS. Clinical features, pulmonary dysfunction and mortality were compared between patients treated with and without ECMO.

Results

Of 18 patients admitted, 6 were treated with veno-venous and 3 with veno-arterial ECMO after median (interquartile, IQR) duration of mechanical ventilation of 10 (6–96) h. Six ECMO were initiated in a referral hospital by a mobile team, a median (IQR) of 3 (2–4) h after phone contact. Before ECMO, patients had severe respiratory failure with median (IQR) PaO₂ to FiO₂ ratio of 52 (50–60) mmHg and PaCO₂ of 85 (69–91) mmHg. Patients treated with or without ECMO had the same hospital mortality rate (56%, 5/9). Duration of ECMO therapy was 9 (4–14) days in survivors and 5 (2–25) days in non-survivors. Early improvement of PaO₂ to FiO₂ ratio was greater in ECMO survivors than non-survivors after ECMO initiation [295 (151–439) versus 131 (106–144) mmHg, p < 0.05]. Haemorrhagic complications occurred in four patients under ECMO, but none required surgical treatment.

Conclusions

ECMO may be an effective salvage treatment for patients with influenza A (H1N1)-related ARDS presenting rapid refractory respiratory failure, particularly when provided by a mobile team allowing early cannulation prior to transfer to a reference centre.     

Lack of association between body weight and mortality in patients on veno-venous extracorporeal membrane oxygenation

Purpose

To analyse the association of body weight with hospital mortality of adult patients supported with veno-venous extracorporeal membrane oxygenation (VV ECMO).

Methods

Retrospective analysis of the international Extracorporeal Life Support Organization (ELSO) registry. Univariate and multivariable logistic regression analyses were used to estimate the odds ratio (OR) of hospital death for each body weight quartile. Adjustment was made for demographic, physiologic and ECMO-related characteristics. We undertook a similar analysis for the subgroup of patients with confirmed H1N1 infection on VV ECMO.

Results

The study group consisted of 1,334 adult patients supported with VV ECMO between 2005 and 2011 with a median (Q1, Q3) body weight of 80 kg (69, 101 kg). Univariate analysis identified increased body weight to be associated with a reduced risk of death. In multivariable analysis, only age greater than 53 years, primary diagnosis other than pneumonia and intubation time longer than 3 days prior to initiation of ECMO were independent risk factors for mortality, whereas the association between high body weight and adjusted risk of death (OR 0.73, 95 % CI 0.52–1.04, P = 0.08) was no longer statistically significant. The body weight of the 196 patients with confirmed H1N1 infection was significantly higher than that of the remaining study group. Body weight was not significantly associated with risk of death for these patients either (univariate OR for Q4 vs. Q1: 0.75, 95 % CI 0.33–1.72, P = 0.49).

Conclusions

Increased body weight was not a risk factor for hospital mortality in adult patients who required support with VV ECMO. High body weight should therefore not be regarded as a contraindication to initiation of VV ECMO in adult patients. Data collection and reporting that include patient height in addition to body weight would facilitate future research into the association of obesity with outcome of ECMO patients.     

Distinct determinants of long-term and short-term survival in critical illness

Purpose

To identify the determinants of short-term and long-term survival in adult patients admitted to intensive care units (ICUs).

Methods

This population-based, observational cohort study included all eleven adult ICUs in the Winnipeg Health Region of Manitoba, Canada, analyzing initial ICU admissions during the period 1999–2010 of all Manitobans ≥17 years old. Analysis included Kaplan–Meier survival curves and multivariable regression models of 30-day mortality and post-90-day survival among those who survived to day 90. We used likelihood ratios to compare the predictive power of clusters of variables in these models.

Results

After 33,324 initial ICU admissions, mortality rates within 30 and 90 days were 15.9 and 19.5 %, respectively. The survival curve demonstrated an early phase with a high rate of death, followed by a markedly lower death rate that was only clearly established after several months. 30-day mortality was predominantly determined by characteristics of the acute illness; with its relative contribution set at 1.00, the next largest contributors were age (0.19) and comorbidity (0.16). In contrast, post-90-day mortality was mainly determined by age (relative contribution 1.00) and comorbidity (0.95); the next largest contributor was characteristics of acute illness (0.28).

Conclusions

We observed two phases of survival related to critical illness. Short-term mortality was mainly determined by the acute illness, but its effect decayed relatively rapidly. Mortality beyond 3 months, among those who survived to that point, was mainly determined by age and comorbidity. Recognition of these findings is relevant to discussions with patients and surrogates about achievable goals of care.     

Wirksamkeit und Wirkungsbeginn von Pregabalin bei Patienten mit neuropathischen Schmerzen

Background

The data from a previously published 12-week randomised, double-blind, placebo-controlled multicentre study on the efficacy and safety of pregabalin were analyzed for time to onset of analgesic action with neuropathic pain.

Patients and methods

A total of 338 patients with postherpetic neuralgia or painful diabetic peripheral neuropathy were treated with flexible or fixed regimens of pregabalin at daily doses of up to 600 mg/day (n=141 and 132, respectively) or placebo (n=65).

Results

Under fixed dose treatment, a decrease of one full point on the 11-point numerical rating pain scale was reached on day 1, two full points on day 13, and three full points on day 23 (under flexible dose pregabalin: on days 6, 17 and 30). In both treatment arms, pain reduction was statistically significant (P=0.001, P=0.002 vs placebo, respectively).

Conclusion

In patients with chronic neuropathic pain, the analgesic effect of both pregabalin treatment regimens was high and associated with a rapid time to onset.     

Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to influenza A (H1N1) pneumonia: the ECMOnet score

Purpose

The decision to start venovenous extracorporeal membrane oxygenation (VV ECMO) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. The aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of VV ECMO initiation.

Methods

This was a prospective multicenter cohort study on 60 patients with influenza A (H1N1)-associated respiratory distress syndrome participating in the Italian ECMOnet data set in the 2009 pandemic. Criteria for ECMO institution were standardized according to national guidelines.

Results

The survival rate in patients treated with ECMO was 68 %. Significant predictors of death before ECMO institution by multivariate analysis were hospital length of stay before ECMO institution (OR = 1.52, 95 % CI 1.12–2.07, p = 0.008); bilirubin (OR = 2.32, 95 % CI 1.52–3.52, p < 0.001), creatinine (OR = 7.38, 95 % CI 1.43–38.11, p = 0.02) and hematocrit values (OR = 0.82, 95 % CI 0.72–0.94, p = 0.006); and mean arterial pressure (OR = 0.92, 95 % CI 0.88–0.97, p < 0.001). The ECMOnet score was developed based on these variables, with a score of 4.5 being the most appropriate cutoff for mortality risk prediction. The high accuracy of the ECMOnet score was further confirmed by ROC analysis (c = 0.857, 95 % CI 0.754–0.959, p < 0.001) and by an independent external validation analysis (c = 0.694, 95 % CI 0.562–0.826, p = 0.004).

Conclusions

Mortality risk for patients receiving VV ECMO is correlated to the extrapulmonary organ function at the time of ECMO initiation. The ECMOnet score is a tool for the evaluation of the appropriateness and timing of VV ECMO in acute lung failure.     

Neurologic complications in neonates supported with extracorporeal membrane oxygenation. An analysis of ELSO registry data

Background

Neurologic complications in neonates supported with extracorporeal membrane oxygenation (ECMO) are common and diminish their quality of life and survival. An understanding of factors associated with neurologic complications in neonatal ECMO is lacking. The goals of this study were to describe the epidemiology and factors associated with neurologic complications in neonatal ECMO.

Patients and methods

Retrospective cohort study of neonates (age ≤30 days) supported with ECMO using data reported to the Extracorporeal Life Support Organization during 2005–2010.

Results

Of 7,190 neonates supported with ECMO, 1,412 (20 %) had neurologic complications. Birth weight <3 kg [odds ratio (OR): 1.3; 95 % confidence intervals (CI): 1.1–1.5], gestational age (<34 weeks; OR 1.5, 95 % CI 1.1–2.0 and 34–36 weeks: OR 1.4, 95 % CI 1.1–1.7), need for cardiopulmonary resuscitation prior to ECMO (OR 1.7, 95 % CI 1.5–2.0), pre-ECMO blood pH ≤ 7.11 (OR 1.7, 95 % CI 1.4–2.1), pre-ECMO bicarbonate use (OR 1.3, 95 % CI 1.2–1.5), prior ECMO exposure (OR 2.4, 95 % CI 1.6–2.6), and use of veno-arterial ECMO (OR 1.7, 95 % CI 1.4–2.0) increased neurologic complications. Mortality was higher in patients with neurologic complications compared to those without (62 % vs. 36 %; p < 0.001).

Conclusions

Neurologic complications are common in neonatal ECMO and are associated with increased mortality. Patient factors, pre-ECMO severity of illness, and use of veno-arterial ECMO are associated with increased neurologic complications. Patient selection, early ECMO deployment, and refining ECMO management strategies for vulnerable populations could be targeted as areas for improvement in neonatal ECMO.     

Clinical impact of arterial ammonia levels in ICU patients with different liver diseases

Purpose

Increased arterial ammonia levels are associated with high mortality in patients with acute liver failure (ALF). Data on the prognostic impact of arterial ammonia is lacking in hypoxic hepatitis (HH) and scarce in critically ill patients with cirrhosis.

Methods

The patient cohort comprised 72 patients with HH, 43 patients with ALF, 100 patients with liver cirrhosis and 45 patients without evidence for liver disease. Arterial ammonia concentrations were assessed on a daily basis in all patients and the results were compared among these four patient groups and between 28-day survivors and 28-day non-survivors overall and in each group.

Results

Overall 28-day mortality rates in patients with HH, ALF and cirrhosis and in the control group were 54, 30, 49 and 27 %, respectively. Peak arterial ammonia levels differed significantly between transplant-free 28-day survivors and non-survivors in the HH and ALF groups (p < 0.01 for both). Multivariate regression identified peak arterial ammonia concentrations as an independent predictor of 28-day mortality or liver transplantation in patients with HH and ALF, respectively (p < 0.01). There was no association between mortality and arterial ammonia in patients with liver cirrhosis and in the control group. Admission arterial ammonia levels were independently linked to hepatic encephalopathy grades 3/4 in patients with HH (p < 0.01), ALF (p < 0.05) and cirrhosis (p < 0.05), respectively.

Conclusions

Elevated arterial ammonia levels indicate a poor prognosis in acute liver injury and are associated with advanced HE in HH, ALF and cirrhosis. Arterial ammonia levels provide additional information in the risk assessment of critically ill patients with liver disease.     

Unresponsive thrombotic thrombocytopenic purpura in critically ill adults

Introduction

The prognosis of thrombotic thrombocytopenic purpura (TTP) has considerably improved since the introduction of plasma exchange (PEX) therapy. However, unresponsive thrombotic thrombocytopenic purpura (Un-TTP) still carries high morbidity and mortality rates, indicating a need for early specific treatments.

Patients and Methods

In a retrospective study including consecutive adults with TTP admitted between January 1997 and January 2011 in a teaching hospital intensive care unit (ICU), our objective here is to identify early clinical and laboratory features predicting Un-TTP. Patients who responded to plasma exchange and steroids (N = 49) were compared with patients with unresponsive TTP defined as requirement for other treatments, protracted course, or death (N = 37, 43 %).

Results

Hospital mortality was 24.3 % in the Un-TTP group. Variables associated with Un-TTP on univariate logistic regression were older age, cardiac involvement, neurological involvement, higher anti-a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS13) immunoglobulin G (IgG) titer, lower platelet counts starting on day 2, higher Sequential Organ Failure Assessment (SOFA) scores starting on day 3, need for higher plasma volumes to obtain remission, and greater use of adjuvant treatments and life-sustaining interventions. Multivariate logistic regression identified four factors independently associated with Un-TTP: age over 60 years [odds ratio (OR) 7.90; 95 % confidence interval (95 % CI) 1.06–78.34], cardiac (OR 5.17; 95 % CI 1.63–16.39) or neurological (OR 8.04; 95 % CI 1.27–51.03) manifestations at diagnosis, and day 2 platelet count less than 15 G/l (OR 3.88; 95 % CI 1.30–11.62).

Conclusion

Therapeutic intensification starting on day 3 or even earlier in patients with the independent risk factors for unresponsive TTP identified in our study deserves evaluation in a multicenter prospective study.     

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.

     

A randomized trial of intravenous glutamine supplementation in trauma ICU patients

Purpose

To evaluate the effect of the intravenous (i.v.) l-alanyl-l-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit (ICU).

Methods

This was a prospective, randomized, double-blind, multicenter trial. Glutamine was not given as a component of nutrition but as an extra infusion. The primary outcome variable was the number of new infections within the first 14 days.

Results

We included 142 patients. There were no differences between groups in baseline characteristics. Up to 62 % of the patients in the placebo group and 63 % in the treatment group presented confirmed infections (p = 0.86). ICU length of stay was 14 days in both groups (p = 0.54). Hospital length of stay was 27 days in the placebo group and 29 in the treatment group (p = 0.88). ICU mortality was 4.2 % in both groups (p = 1). Sixty percent of the patients presented low glutamine levels before randomization. At the end of the treatment (6th day), 48 % of the patients maintained low glutamine levels (39 % of treated patients vs. 57 % in the placebo group). Patients with low glutamine levels at day 6 had more number of infections (58.8 vs. 80.9 %; p = 0.032) and longer ICU (9 vs. 20 days; p < 0.01) and hospital length of stay (24 vs. 41 days; p = 0.01).

Conclusions

There was no benefit with i.v. l-alanyl-l-glutamine dipeptide supplementation (0.5 g/kg body weight/day of the dipeptide) during 5 days in trauma patients admitted to the ICU. The i.v. glutamine supplementation was not enough to normalize the plasma glutamine levels in all patients. Low plasma glutamine levels at day 6 were associated with a worse outcome.     

Effects of hydroxyethyl starch in subgroups of patients with severe sepsis: exploratory post-hoc analyses of a randomised trial

Purpose

It has been speculated that certain subgroups of sepsis patients may benefit from treatment with hydroxyethyl starch (HES) 130/0.42, specifically in the earlier resuscitation of patients with more severely impaired circulation.

Methods

This was a post-hoc, subgroup analysis of all 798 patients with severe sepsis randomised in the 6S trial according to time from ICU admission to randomisation, surgery and fluids given prior to randomisation and markers of shock at randomisation. Intervention effects estimated as risk ratios were analysed between the HES versus Ringer’s acetate groups to detect subgroup heterogeneity of the effects on 90-day mortality. Multiple logistic regression was used to adjust for risk factors.

Results

Most baseline characteristics were comparable between the HES and Ringer’s acetate groups in the different subgroups. There was no heterogeneity in the intervention effect on 90-day mortality in the following subgroups: randomisation earlier than 4 h after ICU admission versus later (test of interaction P = 0.85), surgery versus no surgery (P = 0.42), colloids given versus not given (P = 0.57), <2 l of crystalloids given prior to randomisation vs. >2 l (P = 0.88) or plasma lactate >4 mmol/l versus <4 mmol/l (P = 0.54), hypotension versus no hypotension (P = 0.32) or use of vasopressor or inotropic agents at randomisation versus no use (P = 0.10).

Conclusions

The increased 90-day mortality observed in patients with severe sepsis resuscitated with HES 130/0.42 did not appear to depend on time course, surgery or fluids given prior to randomisation or on markers of shock at randomisation. As the analyses were planned post hoc and their power is reduced, the results should be interpreted with caution.     

Implementation of modified early-goal directed therapy for sepsis in the emergency center of a comprehensive cancer center

Purpose

The investigation examines the impact of a standardized sepsis order set and algorithm utilizing non-invasive monitoring for early-goal directed therapy (EGDT) in an emergency center setting on the clinical outcomes of sepsis in cancer patients.

Methods

Single-center, retrospective study comparing clinical outcomes of sepsis before and after routine usage of a standardized order set and algorithm for non-invasive elements of EGDT for sepsis in an emergency center of a comprehensive cancer center. The outcomes measures evaluated were 28-day in-hospital mortality, intensive care unit length of stay, hospital length of stay, goal mean arterial pressure and urine output within the first 6 h of treatment, time to measurement of lactic acid, and appropriateness and timeliness of initial antibiotic therapy.

Results

The 28-day in-hospital mortality was significantly lower in the post-intervention group compared to the pre-intervention group (20 vs. 38 %, p?=?0.005). The percentages of patients who reached their goal mean arterial pressure (74 vs. 90 %, p?=?0.004) and goal urine output (79 vs. 96 %, p?=?0.002) during the first 6 h of treatment were higher the after than the before group. No significant differences were detected in the rest of the outcome measures.

Conclusions

Implementation of a standardized sepsis order set and algorithm to improve compliance with the non-invasive elements of EGDT for sepsis in cancer patients in the emergency center setting was associated with a decreased 28-day in-hospital mortality rate.     

Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials

Purpose

Data from two randomized trials, evaluating a single-day regimen of palonosetron plus dexamethasone against emesis due to moderately emetogenic chemotherapy, were assessed for the impact of age on outcome in a pooled sample of women receiving anthracycline and/or cyclophosphamide (AC)-containing chemotherapy.

Methods

Chemo-naïve breast cancer patients randomized to receive palonosetron (0.25 mg) plus dexamethasone (8 mg IV) on day 1 of chemotherapy (n?=?200), or the same regimen followed by oral dexamethasone (8 mg) on days 2 and 3 (n?=?205), were included in the analysis. The primary endpoint was complete response (CR: no vomiting and no rescue anti-emetics) in the 5-day study period. The effect of the 1-day regimen and age (<50 and ≥50 years) was investigated by a meta-analysis of individual patient data.

Results

Younger patients comprised 43 % and 49 % of the 1-day and 3-day regimen groups, respectively; 94 % of the pooled sample received the AC combination. There were no between-treatment differences in CR rate according to age during all observation periods. In the 1-day regimen group, 55.2 % of younger patients achieved overall CR compared with 54 % of older patients. In the 3-day regimen group, 51.5 % of younger patients achieved overall CR compared with 58.7 % of older patients. In the adjusted analysis, younger age was not associated with overall CR to treatment (risk difference, ?3.1 %; 95 % CI, ?13.0 to 6.7 %; P?=?0.533).

Conclusions

These results provide evidence that, irrespective of age, the dexamethasone-sparing regimen is not associated with a significant loss in overall anti-emetic protection in women undergoing AC-containing chemotherapy.     

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.     

Associations between ventilator settings during extracorporeal membrane oxygenation for refractory hypoxemia and outcome in patients with acute respiratory distress syndrome: a pooled individual patient data analysis

Purpose

Extracorporeal membrane oxygenation (ECMO) is a rescue therapy for patients with acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate associations between ventilatory settings during ECMO for refractory hypoxemia and outcome in ARDS patients.

Methods

In this individual patient data meta-analysis of observational studies in adult ARDS patients receiving ECMO for refractory hypoxemia, a time-dependent frailty model was used to determine which ventilator settings in the first 3 days of ECMO had an independent association with in-hospital mortality.

Results

Nine studies including 545 patients were included. Initiation of ECMO was accompanied by significant decreases in tidal volume size, positive end-expiratory pressure (PEEP), plateau pressure, and driving pressure (plateau pressure ? PEEP) levels, and respiratory rate and minute ventilation, and resulted in higher PaO₂/FiO₂, higher arterial pH and lower PaCO₂ levels. Higher age, male gender and lower body mass index were independently associated with mortality. Driving pressure was the only ventilatory parameter during ECMO that showed an independent association with in-hospital mortality [adjusted HR, 1.06 (95 % CI, 1.03–1.10)].

Conclusion

In this series of ARDS patients receiving ECMO for refractory hypoxemia, driving pressure during ECMO was the only ventilator setting that showed an independent association with in-hospital mortality.

     

Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units: the FINNAKI study

Purpose

We aimed to determine the incidence, risk factors and outcome of acute kidney injury (AKI) in Finnish ICUs.

Methods

This prospective, observational, multi-centre study comprised adult emergency admissions and elective patients whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. We defined AKI first by the Acute Kidney Injury Network (AKIN) criteria supplemented with a baseline creatinine and second with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We screened the patients’ AKI status and risk factors for up to 5 days.

Results

We included 2,901 patients. The incidence (95 % confidence interval) of AKI was 39.3 % (37.5–41.1 %). The incidence was 17.2 % (15.8–18.6 %) for stage 1, 8.0 % (7.0–9.0 %) for stage 2 and 14.1 % (12.8–15.4 %) for stage 3 AKI. Of the 2,901 patients 296 [10.2 % (9.1–11.3 %)] received renal replacement therapy. We received an identical classification with the new KDIGO criteria. The population-based incidence (95 % CI) of ICU-treated AKI was 746 (717–774) per million population per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease were independent risk factors for AKI. Hospital mortality (95 % CI) for AKI patients was 25.6 % (23.0–28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9–36.5 %). All AKIN stages were independently associated with 90-day mortality.

Conclusions

The incidence of AKI in the critically ill in Finland was comparable to previous large multi-centre ICU studies. Hospital mortality (26 %) in AKI patients appeared comparable to or lower than in other studies.