At-Risk Drinking Is Independently Associated With Acute Kidney Injury in Critically Ill Patients

At-Risk Drinking Is Independently Associated With Acute Kidney Injury in Critically Ill Patients

by Gacouin, Arnaud; Lesouhaitier, Mathieu; Frerou, Aurelien; Painvin, Benoit; Reizine, Florian; Rafi, Sonia; Maamar, Adel; Le Tulzo, Yves; Tadié, Jean Marc

Critical Care Medicine: August 2019 - Volume 47 - Issue 8 - p 1041-1049

Objectives: Unhealthy use of alcohol and acute kidney injury are major public health problems, but little is known about the impact of excessive alcohol consumption on kidney function in critically ill patients. We aimed to determine whether at-risk drinking is independently associated with acute kidney injury in the ICU and at ICU discharge.

Design: Prospective observational cohort study. Setting: A 21-bed polyvalent ICU in a university hospital. Patients: A total of 1,107 adult patients admitted over a 30-month period who had an ICU stay of greater than or equal to 3 days and in whom alcohol consumption could be assessed. Interventions: None.

Measurements and Main Results: We assessed Kidney Disease Improving Global Outcomes stages 2–3 acute kidney injury in 320 at-risk drinkers (29%) and 787 non–at-risk drinkers (71%) at admission to the ICU, within 4 days after admission and at ICU discharge. The proportion of patients with stages 2–3 acute kidney injury at admission to the ICU (42.5% vs 18%; p < 0.0001) was significantly higher in at-risk drinkers than in non–at-risk drinkers. Within 4 days and after adjustment on susceptible and predisposing factors for acute kidney injury was performed, at-risk drinking was significantly associated with acute kidney injury for the entire population (odds ratio, 2.15; 1.60–2.89; p < 0.0001) in the subgroup of 832 patients without stages 2–3 acute kidney injury at admission to the ICU (odds ratio, 1.44; 1.02–2.02; p = 0.04) and in the subgroup of 971 patients without known chronic kidney disease (odds ratio, 1.92; 1.41–2.61; p < 0.0001). Among survivors, 22% of at-risk drinkers and 9% of non–at-risk drinkers were discharged with stages 2–3 acute kidney injury (p < 0.001).

Conclusions: Our results suggest that chronic and current alcohol misuse in critically ill patients is associated with kidney dysfunction. The systematic and accurate identification of patients with alcohol misuse may allow for the prevention of acute kidney injury.

The end-expiratory occlusion test: please, let me hold your breath!

The end-expiratory occlusion test: please, let me hold your breath!

by Francesco Gavelli, Jean-Louis Teboul and Xavier Monnet 

Critical Care:  volume 23, Article number: 274 (2019) 

Introduction

Fluids must be considered as drugs, with serious adverse effects and inconstant efficacy. Then, they should be administered only if there is reasonable chance that cardiac output (CO) will increase in response. Many tests or indices detecting “fluid responsiveness” have been developed for this purpose.

With some of these tests, the relationship between CO and cardiac preload is assessed through the haemodynamic effects of mechanical ventilation. It is the case for the end-expiratory occlusion (EEO) test, which has already been investigated in a reasonable number of studies [1,2,3,4,5,6,7,8,9,10,11,12,13]. In this commentary, we will explore its haemodynamic effects, review the literature validating it and describe its practical modalities.

Abdominal functional electrical stimulation to assist ventilator weaning in critical illness: a double-blinded, randomised, sham-controlled pilot study

Abdominal functional electrical stimulation to assist ventilator weaning in critical illness: a double-blinded, randomised, sham-controlled pilot study

by Euan J. McCaughey, Annemijn H. Jonkman, Claire L. Boswell-Ruys, Rachel A. McBain, Elizabeth A. Bye, Anna L. Hudson, David W. Collins, Leo M. A. Heunks, Angus J. McLachlan, Simon C. Gandevia and Jane E. Butler

Critical Care:  volume 23, Article number: 261 (2019)

Background:

For every day a person is dependent on mechanical ventilation, respiratory and cardiac complications increase, quality of life decreases and costs increase by > $USD 1500. Interventions that improve respiratory muscle function during mechanical ventilation can reduce ventilation duration. The aim of this pilot study was to assess the feasibility of employing an abdominal functional electrical stimulation (abdominal FES) training program with critically ill mechanically ventilated patients. We also investigated the effect of abdominal FES on respiratory muscle atrophy, mechanical ventilation duration and intensive care unit (ICU) length of stay.

Methods:

Twenty critically ill mechanically ventilated participants were recruited over a 6-month period from one metropolitan teaching hospital. They were randomly assigned to receive active or sham (control) abdominal FES for 30 min, twice per day, 5 days per week, until ICU discharge. Feasibility was assessed through participant compliance to stimulation sessions. Abdominal and diaphragm muscle thickness were measured using ultrasound 3 times in the first week, and weekly thereafter by a blinded assessor. Respiratory function was recorded when the participant could first breathe independently and at ICU discharge, with ventilation duration and ICU length of stay also recorded at ICU discharge by a blinded assessor.

Results:

Fourteen of 20 participants survived to ICU discharge (8, intervention; 6, control). One control was transferred before extubation, while one withdrew consent and one was withdrawn for staff safety after extubation. Median compliance to stimulation sessions was 92.1% (IQR 5.77%) in the intervention group, and 97.2% (IQR 7.40%) in the control group (p = 0.384). While this pilot study is not adequately powered to make an accurate statistical conclusion, there appeared to be no between-group thickness changes of the rectus abdominis (p = 0.099 at day 3), diaphragm (p = 0.652 at day 3) or combined lateral abdominal muscles (p = 0.074 at day 3). However, ICU length of stay (p = 0.011) and ventilation duration (p = 0.039) appeared to be shorter in the intervention compared to the control group.

Conclusions:

Our compliance rates demonstrate the feasibility of using abdominal FES with critically ill mechanically ventilated patients. While abdominal FES did not lead to differences in abdominal muscle or diaphragm thickness, it may be an effective method to reduce ventilation duration and ICU length of stay in this patient group. A fully powered study into this effect is warranted.

Trial registration:

The Australian New Zealand Clinical Trials Registry, ACTRN12617001180303. Registered 9 August 2017.

Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis

Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis

by Alexandros Rovas, Laura Mareen Seidel, Hans Vink, Timo Pohlkötter, Hermann Pavenstädt, Christian Ertmer, Michael Hessler and Philipp Kümpers

Critical Care: volume 23, Article number: 260 (2019) 

Background:

The endothelial glycocalyx (eGC) covers the luminal surface of the vascular endothelium and plays an important protective role in systemic inflammatory states and particularly in sepsis. Its breakdown leads to capillary leak and organ dysfunction. Moreover, sepsis-induced alterations of sublingual microcirculation are associated with a worse clinical outcome. The present study was performed to investigate the associations between eGC dimensions and established parameters of microcirculation dysfunction in sepsis.

Methods:

This observational, prospective, cross-sectional study included 40 participants, of which 30 critically ill septic patients were recruited from intensive care units of a university hospital and 10 healthy volunteers served as controls. The established microcirculation parameters were obtained sublingually and analyzed according to the current recommendations. In addition, the perfused boundary region (PBR), an inverse parameter of the eGC dimensions, was measured sublingually, using novel data acquisition and analysis software (GlycoCheck™). Moreover, we exposed living endothelial cells to 5% serum from a subgroup of study participants, and the delta eGC breakdown, measured with atomic force microscopy (AFM), was correlated with the paired PBR values.

Results:

In septic patients, sublingual microcirculation was impaired, as indicated by a reduced microvascular flow index (MFI) and a reduced proportion of perfused vessels (PPV) compared to those in healthy controls (MFI, 2.93 vs 2.74, p = 0.002; PPV, 98.53 vs 92.58, p = 0.0004). PBR values were significantly higher in septic patients compared to those in healthy controls, indicating damage of the eGC (2.04 vs 2.34, p < 0.0001). The in vitro AFM data correlated exceptionally well with paired PBR values obtained at the bedside (rs = − 0.94, p = 0.02). Both PBR values and microcirculation parameters correlated well with the markers of critical illness. Interestingly, no association was observed between the PBR values and established microcirculation parameters.

Conclusion:

Our findings suggest that eGC damage can occur independently of microcirculatory impairment as measured by classical consensus parameters. Further studies in critically ill patients are needed to unravel the relationship of glycocalyx damage and microvascular impairment, as well as their prognostic and therapeutic importance in sepsis.

Trial registration:

Retrospectively registered: Clinicaltrials.gov, NCT03960307

Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation

Intravenous fluid resuscitation is associated with septic endothelial glycocalyx degradation

by Joseph A. Hippensteel, Ryo Uchimido, Patrick D. Tyler, Ryan C. Burke, Xiaorui Han, Fuming Zhang, Sarah A. McMurtry, James F. Colbert, Christopher J. Lindsell, Derek C. Angus, John A. Kellum, Donald M. Yealy, Robert J. Linhardt, Nathan I. Shapiro and Eric P. Schmidt

Critical Care  volume 23, Article number: 259 (2019) 

Background:

Intravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfate-enriched structure necessary for vascular homeostasis. We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation.

Methods:

We used mass spectrometry to measure plasma eparin sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. We compared plasma eparin sulfate concentrations between sepsis and non-sepsis patients, as well as between sepsis survivors and sepsis non-survivors. We used multivariable linear regression to model the association between volume of intravenous fluids and changes in plasma eparin sulfate.

Results:

Consistent with previous studies, median plasma heparan sulfate was elevated in septic shock patients (118 [IQR, 113–341] ng/ml 6 h after presentation) compared to non-infected controls (61 [45–79] ng/ml), as well as in a second cohort of sepsis patients (283 [155–584] ng/ml) at emergency department presentation) compared to controls (177 [144–262] ng/ml). In the larger sepsis cohort, heparan sulfate predicted in-hospital mortality. In both cohorts, multivariable linear regression adjusting for age and severity of illness demonstrated a significant association between volume of intravenous fluids administered during resuscitation and plasma heparan sulfate. In the second cohort, independent of disease severity and age, each 1 l of intravenous fluids administered was associated with a 200 ng/ml increase in circulating heparan sulfate (p = 0.006) at 24 h after enrollment.

Conclusions:

Glycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. The volume of intravenous fluids administered during sepsis resuscitation is independently associated with the degree of glycocalyx degradation. These findings suggest a potential mechanism by which intravenous fluid resuscitation strategies may induce iatrogenic endothelial injury.

Noninvasive assessment of airflows by electrical impedance tomography in intubated hypoxemic patients: an exploratory study

Noninvasive assessment of airflows by electrical impedance tomography in intubated hypoxemic patients: an exploratory study

by Tommaso Mauri, Elena Spinelli, Francesca Dalla Corte, Eleonora Scotti, Cecilia Turrini, Marta Lazzeri, Laura Alban, Marco Albanese, Donatella Tortolani, Yu-Mei Wang, Savino Spadaro, Jian-Xin Zhou, Antonio Pesenti and Giacomo Grasselli

Annals of Intensive Care: volume 9, Article number: 83 (2019) 

Background:

Noninvasive monitoring of maximal inspiratory and expiratory flows (MIF and MEF, respectively) by electrical impedance tomography (EIT) might enable early recognition of changes in the mechanical properties of the respiratory system due to new conditions or in response to treatments. We aimed to validate EIT-based measures of MIF and MEF against spirometry in intubated hypoxemic patients during controlled ventilation and spontaneous breathing. Moreover, regional distribution of maximal airflows might interact with lung pathology and increase the risk of additional ventilation injury. Thus, we also aimed to describe the effects of mechanical ventilation settings on regional MIF and MEF.

Methods:

We performed a new analysis of data from two prospective, randomized, crossover studies. We included intubated patients admitted to the intensive care unit with acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) undergoing pressure support ventilation (PSV, n = 10) and volume-controlled ventilation (VCV, n = 20). We measured MIF and MEF by spirometry and EIT during six different combinations of ventilation settings: higher vs. lower support during PSV and higher vs. lower positive end-expiratory pressure (PEEP) during both PSV and VCV. Regional airflows were assessed by EIT in dependent and non-dependent lung regions, too.

Results:

MIF and MEF measured by EIT were tightly correlated with those measured by spirometry during all conditions (range of R2 0.629–0.776 and R2 0.606–0.772, respectively, p < 0.05 for all), with clinically acceptable limits of agreement. Higher PEEP significantly improved homogeneity in the regional distribution of MIF and MEF during volume-controlled ventilation, by increasing airflows in the dependent lung regions and lowering them in the non-dependent ones.

Conclusions:

EIT provides accurate noninvasive monitoring of MIF and MEF. The present study also generates the hypothesis that EIT could guide PSV and PEEP settings aimed to increase homogeneity of distending and deflating regional airflows.

Impact of Structured Pathways for Postcardiac Arrest Care: A Systematic Review and Meta-Analysis

Impact of Structured Pathways for Postcardiac Arrest Care: A Systematic Review and Meta-Analysis

by Storm, Christian; Leithner, Christoph; Krannich, Alexander; Suarez, Jose I.; Stevens, Robert D. 

Critical Care Medicine: August 2019 - Volume 47 - Issue 8 - p e710-e716

Objectives: Recent research has demonstrated value in selected therapeutic and prognostic interventions delivered to patients following cardiac arrest. The aim of this work was to determine if the implementation of a structured care pathway, which combines different interventions, could improve outcomes in survivors of cardiac arrest.

Data Sources: PubMed and review of citations in retrieved articles.

Study Selection: Randomized trials and prospective observational studies conducted in adult cardiac arrest patients, which evaluated the impact on outcome of a structured care pathway, defined as an organized set of interventions designed specifically for postcardiac arrest patients.

Data Extraction: Data collected included study characteristics and methodologic quality, populations enrolled, interventions that were part of the cardiac arrest structured care pathway, and outcomes. The principal outcome was favorable functional status defined as a Cerebral Performance Category score of 1–2 at or after hospital discharge.

Data Synthesis: The systematic search retrieved 481 articles of which nine (total, 1,994 patients) were selected for systematic review, and six (1,422 patients) met criteria for meta-analysis. Interventions in the care pathways included early coronary angiography with or without percutaneous coronary intervention (eight studies), targeted temperature management (nine studies), and protocolized management in the ICU (seven studies). Neurologic prognostication was not a part of any of the structured pathways. Meta-analysis found significantly higher odds of achieving a favorable functional outcome in patients who were treated in a structured care pathway, when compared with standard care (odds ratio, 2.35; 95% CI, 1.46–3.81).

Conclusions: Following cardiac arrest, patients treated in a structured care pathway may have a substantially higher likelihood of favorable functional outcome than those who receive standard care. These findings suggest benefit of a highly organized approach to postcardiac arrest care, in which a cluster of evidence-based interventions are delivered by a specialized interdisciplinary team. Given the overall low certainty of evidence, definitive recommendations will need confirmation in additional high-quality studies.

Early Enteral Nutrition in Patients Undergoing Sustained Neuromuscular Blockade: A Propensity-Matched Analysis Using a Nationwide Inpatient Database*

Early Enteral Nutrition in Patients Undergoing Sustained Neuromuscular Blockade: A Propensity-Matched Analysis Using a Nationwide Inpatient Database*

By Ohbe, Hiroyuki; Jo, Taisuke; Matsui, Hiroki; Fushimi, Kiyohide; Yasunaga, Hideo 

Critical Care Medicine: August 2019 - Volume 47 - Issue 8 - p 1072-1080

Objectives: Whether enteral nutrition should be postponed in patients undergoing sustained treatment with neuromuscular blocking agents remains unclear. We evaluated the association between enteral nutrition initiated within 2 days of sustained neuromuscular blocking agent treatment and in-hospital mortality.

Design: Retrospective administrative database study from July 2010 to March 2016. Setting: More than 1,200 acute care hospitals covering approximately 90% of all tertiary-care emergency hospitals in Japan.

Patients: Mechanically ventilated patients, who had undergone sustained treatment with neuromuscular blocking agents in an ICU, were retrospectively reviewed. We defined patients who received sustained treatment with neuromuscular blocking agents as those who received either rocuronium at greater than or equal to 250 mg/d or vecuronium at greater than or equal to 50 mg/d for at least 2 consecutive days. Interventions: Enteral nutrition started within 2 days from the initiation of neuromuscular blocking agents (defined as early enteral nutrition).

Measurements and Main Results: We identified 2,340 eligible patients during the 69-month study period. Of these, 378 patients (16%) had received early enteral nutrition. One-to-three propensity score matching created 374–1,122 pairs. The in-hospital mortality rate was significantly lower in the early than late enteral nutrition group (risk difference, –6.3%; 95% CI, –11.7% to –0.9%). There was no significant difference in the rate of hospital pneumonia between the two groups (risk difference, 2.8%; 95% CI, –2.7% to 8.3%). Length of hospital stay among survivors was significantly shorter in the early compared with the late enteral nutrition group (risk difference, –11.4 d; 95% CI, –19.1 to –3.7 d). There was no significant difference between the two groups in length of ICU stay or length of mechanical ventilation among survivors.

Conclusions: According to this retrospective database study, early enteral nutrition may be associated with lower in-hospital mortality with no increase in-hospital pneumonia in patients undergoing sustained treatment with neuromuscular blocking agents.

Extracorporeal Membrane Oxygenation for Septic Shock

Extracorporeal Membrane Oxygenation for Septic Shock

by Falk, Lars; Hultman, Jan; Broman, Lars Mikael 

Critical Care Medicine: August 2019 - Volume 47 - Issue 8 - p 1097-1105

Objectives: Septic shock carries a high mortality risk. Studies have indicated that patients with septic shock may benefit from extracorporeal membrane oxygenation. In most studies, patients exhibited shock due to myocardial dysfunction rather than distributive/vasoplegic shock. One proposed theory is that venoarterial extracorporeal membrane oxygenation alleviates a failing myocardial function. Design: Retrospective observational study.

Setting: Single-center, high-volume extracorporeal membrane oxygenation unit.

Patients: All patients treated for septic shock between 2012 and 2017 with an age greater than 18 years old, fulfilling septic shock criteria according to “Sepsis-3” at acceptance for extracorporeal membrane oxygenation, presence of cardiocirculatory failure requiring a support equivalent to a Vasoactive Inotropic Score greater than 50 to reach a mean arterial pressure greater than 65 mm Hg despite adequate fluid resuscitation, were included. Interventions: None.

Measurements and Main Results: Thirty-seven patients, mean age 54.7 years old, were included. Median Simplified Acute Physiology Score-3 score was 86 and Sequential Organ Failure Assessment 16. Twenty-seven patients were submitted to venoarterial and 10 patients to venovenous extracorporeal membrane oxygenation. Hospital survival was 90% for septic shock with left ventricular failure and 64.7% in patients with distributive shock. At long-term follow-up at 46.1 months, total survival was 59.5%. Commencement of venovenous extracorporeal membrane oxygenation and more organ failures at admission showed a less favorable outcome in terms of hospital and long-term survival.

Conclusions: The current results add not only to the growing evidence of the benefit of venoarterial extracorporeal membrane oxygenation for septic cardiomyopathy but also indicate improved hospital survival in distributive septic shock.

Monocyte Distribution Width: A Novel Indicator of Sepsis-2 and Sepsis-3 in High-Risk Emergency Department Patients*

Monocyte Distribution Width: A Novel Indicator of Sepsis-2 and Sepsis-3 in High-Risk Emergency Department Patients*

by Crouser, Elliott D.; Parrillo, Joseph E.; Seymour, Christopher W.; Angus, Derek C.; Bicking, Keri; Esguerra, Vincent G.; Peck-Palmer, Octavia M.; Magari, Robert T.; Julian, Mark W.; Kleven, Jennifer M.; Raj, Paarth J.; Procopio, Gabrielle; Careaga, Diana; Tejidor, Liliana

Critical Care Medicine: August 2019 - Volume 47 - Issue 8 - p 1018-1025

Objectives: Most septic patients are initially encountered in the emergency department where sepsis recognition is often delayed, in part due to the lack of effective biomarkers. This study evaluated the diagnostic accuracy of peripheral blood monocyte distribution width alone and in combination with WBC count for early sepsis detection in the emergency department. Design: An Institutional Review Board approved, blinded, observational, prospective cohort study conducted between April 2017 and January 2018.

Setting: Subjects were enrolled from emergency departments at three U.S. academic centers. Patients: Adult patients, 18–89 years, with complete blood count performed upon presentation to the emergency department, and who remained hospitalized for at least 12 hours. A total of 2,212 patients were screened, of whom 2,158 subjects were enrolled and categorized per Sepsis-2 criteria, such as controls (n = 1,088), systemic inflammatory response syndrome (n = 441), infection (n = 244), and sepsis (n = 385), and Sepsis-3 criteria, such as control (n = 1,529), infection (n = 386), and sepsis (n = 243). Interventions: The primary outcome determined whether an monocyte distribution width of greater than 20.0 U, alone or in combination with WBC, improves early sepsis detection by Sepsis-2 criteria. Secondary endpoints determined monocyte distribution width performance for Sepsis-3 detection.

Measurements and Main Results: Monocyte distribution width greater than 20.0 U distinguished sepsis from all other conditions based on either Sepsis-2 criteria (area under the curve, 0.79; 95% CI, 0.76–0.82) or Sepsis-3 criteria (area under the curve, 0.73; 95% CI, 0.69–0.76). The negative predictive values for monocyte distribution width less than or equal to 20 U for Sepsis-2 and Sepsis-3 were 93% and 94%, respectively. Monocyte distribution width greater than 20.0 U combined with an abnormal WBC further improved Sepsis-2 detection (area under the curve, 0.85; 95% CI, 0.83–0.88) and as reflected by likelihood ratio and added value analyses. Normal WBC and monocyte distribution width inferred a six-fold lower sepsis probability.

Conclusions: An monocyte distribution width value of greater than 20.0 U is effective for sepsis detection, based on either Sepsis-2 criteria or Sepsis-3 criteria, during the initial emergency department encounter. In tandem with WBC, monocyte distribution width is further predicted to enhance medical decision making during early sepsis management in the emergency department.