A 59-year-old man with a history of atrial fibrillation and treated obstructive sleep apnea presented to the emergency department on March 26, 2020 with fever, dry cough, dyspnea and headache. He had ...no history of personal or familial seizures. A first reverse-transcriptase–polymerase-chain-reaction (RT-PCR) of nasopharyngeal swab test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was negative but SARS-CoV-2 infection was subsequently confirmed by RT-PCR assay performed on tracheal secretions and by computed tomography scan of the chest. The illness rapidly progressed to hypoxemic respiratory failure warranting the initiation of invasive mechanical ventilation on March 28. Lung bacterial overinfection by Hafnia alveii and Proteus vulgaris was diagnosed and sequentially treated with amoxicillin-clavulanic acid/rovamycine (7 days), tazobactam-piperacillin (5 days) and finally with cefepime (7 days). Deep sedation with midazolam was stopped on April 8 and the patient was extubated the following day.From April 10, the patient started to exhibit short episodes of impaired consciousness together with confusion and behavioral disturbances. Forty-nine minute electroencephalogram (EEG), performed when the patient was awake but confused, showed background fluctuating alertness with preserved responses to simple orders (Fig. 1b) and two widespread long rhythmic delta discharges with superimposed spikes in predominantly frontal localization simultaneous with impaired awareness (Fig. 1c), highly suggestive of epileptic seizures. The first seizure lasted 6 minutes (Fig. 1c), followed by a moderate interictal frontal activity (Fig. 1d) and the second seizure lasted at least 5 minutes (Fig. 1e), leading to the diagnosis of non-convulsive status epilepticus. Laboratory blood tests and brain MRI were normal; plasma cefepime concentrations were within the normal range. Routine cerebrospinal fluid (CSF) analysis was unremarkable and CSF SARS-CoV2 RT-PCR was negative. Clobazam (30 mg/day) and levetiracetam (1.5 g/day) were introduced. On April 14, the patient had only one brief episode of impaired consciousness and his long-term EEG monitoring was normal. He is now clinically stable and discharged from ICU.
Fluid overload has been associated with increased morbidity and mortality in critically ill patients. The goal of this study was to assess the efficacy and safety of a diuretic strategy to overcome ...positive fluid balance in patients on invasive mechanical ventilation.
Design: Multicenter, single-blind, randomized-controlled study. Patients were randomized into a diuretic (furosemide) or a control group. Patients were eligible in case of fluid overload defined as in-ICU weight increase ≥ 3%, invasive mechanical ventilation (FiO
≤ 60% and PEEP ≤ 10 cm H
O on inclusion) and hemodynamic stabilization. The primary outcome was fluid balance, defined as weight variation from reference weight to successful extubation. The main secondary outcome was the safety of diuretic.
171 patients were randomized. After 5 exclusions, 166 patients were included in the analysis: 77 in the diuretic and 89 in the control group. Fluid balance was 1.4 - 2.5 to 4.5 kg in the diuretic and 6.4 0.5-11.2 kg in the control group (p < 0.001). In the multiple imputation analysis, fluid balance was significantly decreased in the diuretic group (mean difference = - 4.8 95% CI - 7.3 to - 2.5, p < 0.001). Eleven (14%) patients died in the diuretic group and 16 (18%) patients in the control group (p = 0.5). There was a worsening of Acute Kidney Injury in 67 (75.3%) patients of the control group versus 46 (59.7%) patients in the diuretic group (p = 0.03).
In this multicenter randomized-controlled study, protocolized diuretic therapy reduced fluid accumulation in patients receiving mechanical ventilation and was well tolerated with a favorable safety profile. Trial registration NCT02345681, Registered January 26 2015, Prospectively registered, https://clinicaltrials.gov/ct2/show/NCT02345681?term=02345681&draw=2&rank=1 .
To propose a combination of blood biomarkers for the prediction of hospital-acquired pneumonia (HAP) and for the selection of traumatic brain-injured (TBI) patients eligible for corticosteroid ...therapy for the prevention of HAP.
This was a sub-study of the CORTI-TC trial, a multicenter, randomized, double-blind, controlled trial evaluating the risk of HAP at day 28 in 336 TBI patients treated or not with corticosteroid therapy. Patients were between 15 and 65 years with severe traumatic brain injury (Glasgow coma scale score ≤ 8 and trauma-associated lesion on brain CT scan) and were enrolled within 24 h of trauma. The blood levels of CRP and cortisol
as a surrogate marker of the pro/anti-inflammatory response balance, were measured in samples collected before the treatment initiation. Endpoint was HAP on day 28.
Of the 179 patients with available samples, 89 (49.7%) developed an HAP. Cortisol
and CRP blood levels upon ICU admission were not significantly different between patients with or without HAP. The cortisol
/CRP ratio upon admission was 2.30 1.25-3.91 in patients without HAP and 3.36 1.74-5.09 in patients with HAP (p = 0.021). In multivariate analysis, a cortisol
/CRP ratio > 3, selected upon the best Youden index on the ROC curve, was independently associated with HAP (OR 2.50, CI95% 1.34-4.64 p = 0.004). The HR for HAP with corticosteroid treatment was 0.59 (CI95% 0.34-1.00, p = 0.005) in patients with a cortisol
/CRP ratio > 3, and 0.89 (CI95% 0.49-1.64, p = 0.85) in patients with a ratio < 3.
A cortisol
/CRP ratio > 3 upon admission may predict the development of HAP in severe TBI. Among these patients, corticosteroids reduce the occurrence HAP. We suggest that this ratio may select the patients who may benefit from corticosteroid therapy for the prevention of HAP.
Patients with brain injury are at high risk of extubation failure.
We conducted a prospective observational cohort study in four intensive care units of three university hospitals. The aim of the ...study was to create a score that could predict extubation success in patients with brain injury.
A total of 437 consecutive patients with brain injury were included, and 338 patients (77.3%) displayed successful extubation. In the multivariate analysis, four features were associated with success the day of extubation: age less than 40 yr, visual pursuit, swallowing attempts, and a Glasgow coma score greater than 10. In the score, each item counted as one. A score of 3 or greater was associated with 90% extubation success. The area under the receiver-operator curve was 0.75 (95% CI, 0.69 to 0.81). After internal validation by bootstrap, the area under the receiver-operator curve was 0.73 (95% CI, 0.68 to 0.79). Extubation success was significantly associated with shorter duration of mechanical ventilation (11 95% CI, 5 to 17 days vs. 22 days 95% CI, 13 to 29 days; P < 0.0001), shorter intensive care unit length of stay (15 95% CI, 9 to 23 days vs. 27 days 95% CI, 21 to 36 days; P < 0.0001), and lower in-intensive care unit mortality (4 1.2% vs. 11 11.1%; P < 0.0001).
Our score exploring both airway functions and neurologic status may increase the probability of successful extubation in patients with severe brain injury.
Purpose
Preoxygenation with high-flow therapy by nasal cannulae (HFNC) is now widespread in the intensive care unit (ICU). However, no large randomized study has assessed its relevance in ...non-severely hypoxemic patients. In a randomized controlled trial (PROTRACH study), we aimed to evaluate preoxygenation with HFNC vs. standard bag-valve mask oxygenation (SMO) in non-severely hypoxemic patients during rapid sequence intubation (RSI) in the ICU.
Methods
Randomized controlled trial including non-severely hypoxemic patients requiring intubation in the ICU. Patients received preoxygenation by HFNC or SMO during RSI. HFNC was maintained throughout the intubation procedure whereas SMO was removed to perform laryngoscopy. The primary outcome was the lowest pulse oximetry (SpO
2
) throughout the intubation procedure. Secondary outcomes included drop in SpO
2
, adverse events related to intubation, and outcome in the ICU.
Results
A total of 192 patients were randomized. In the intent-to-treat analysis, 184 patients (HFNC
n
= 95; SMO
n
= 89), the median IQR lowest SpO
2
was 100% 97; 100 for HFNC and 99% 95; 100 for the SMO group (
P
= 0.30). Mild desaturation below 95% was more frequent with SMO (23%) than with HFNC (12%) (RR 0.51, 95% CI 0.26–0.99,
P
= 0.045). There were fewer adverse events in the HFNC group (6%) than in the SMO group (19%) (RR 0.31, 95% CI 0.13–0.76,
P
= 0.007), including fewer severe adverse events, respectively 6 (6%) and 14 (16%) with HFNC and SMO (RR 0.38, 95% CI 0.15–0.95,
P
= 0.03).
Conclusions
Compared with SMO, preoxygenation with HFNC in the ICU did not improve the lowest SpO
2
during intubation in the non-severely hypoxemic patients but led to a reduction in intubation-related adverse events.
Trial registration
Clinical trial Submission: 7 March 2016. Registry name: Benefits of high-flow nasal cannulae oxygen for preoxygenation during intubation in non-severely hypoxemic patients: the PROTRACH study. Clinicaltrials.gov identifier: NCT02700321. Eudra CT: 2015-A00145-44. CPP: 15/13-975 (Comité de protection des personnes de Rennes). URL registry:
https://clinicaltrials.gov/ct2/show/record/NCT02700321
.
Current guidelines suggest the introduction of early nutrition support within the first 48 h of admission to the intensive care unit (ICU) for patients who cannot eat. In that context, we aimed to ...describe nutrition practices in the ICU and study the association between the introduction of early nutrition support (< 48 h) in the ICU and patient mortality at day 28 (D28) using data from a multicentre prospective cohort.
The 'French-Speaking ICU Nutritional Survey' (FRANS) study was conducted in 26 ICUs in France and Belgium over 3 months in 2015. Adult patients with a predicted ICU length of stay > 3 days were consecutively included and followed for 10 days. Their mortality was assessed at D28. We investigated the association between early nutrition (< 48 h) and mortality at D28 using univariate and multivariate propensity-score-weighted logistic regression analyses.
During the study period, 1206 patients were included. Early nutrition support was administered to 718 patients (59.5%), with 504 patients receiving enteral nutrition and 214 parenteral nutrition. Early nutrition was more frequently prescribed in the presence of multiple organ failure and less frequently in overweight and obese patients. Early nutrition was significantly associated with D28 mortality in the univariate analysis (crude odds ratio (OR) 1.69, 95% confidence interval (CI) 1.23-2.34) and propensity-weighted multivariate analysis (adjusted OR (aOR) 1.05, 95% CI 1.00-1.10). In subgroup analyses, this association was stronger in patients ≤ 65 years and with SOFA scores ≤ 8. Compared with no early nutrition, a significant association was found of D28 mortality with early enteral (aOR 1.06, 95% CI 1.01-1.11) but not early parenteral nutrition (aOR 1.04, 95% CI 0.98-1.11).
In this prospective cohort study, early nutrition support in the ICU was significantly associated with increased mortality at D28, particularly in younger patients with less severe disease. Compared to no early nutrition, only early enteral nutrition appeared to be associated with increased mortality. Such findings are in contrast with current guidelines on the provision of early nutrition support in the ICU and may challenge our current practices, particularly concerning patients at low nutrition risk. Trial registration ClinicalTrials.gov Identifier: NCT02599948. Retrospectively registered on November 5th 2015.
•Critically burn patients usually undergo prolonged and important doses of hypnotics and opioids.•Analgesia and sedation can be titrated according to clinical scales in burn ...patients.•Analgesia-sedation titration failed to decrease mechanical ventilation duration.
Severe burn patients undergo prolonged administration of sedatives and analgesics for burn care. There are currently no guidelines for the dose adaptation of sedation-analgesia in severe burn patients.
We performed a before-after 2-center study to demonstrate the feasibility and efficacy of a sedation-analgesia scale-based protocol in severely burned patients receiving ≥24h of invasive mechanical ventilation. Before the intervention, continuous infusion of hypnotic and morphine derivatives was continued. During the Intervention phase, general anesthesia was relayed from day 1 by RASS/BPS-titrated continuous infusion of hypnotic and morphine derivatives and with short half-life drugs adminstered for daily burn dressings. The primary outcome was the duration of invasive mechanical ventilation in the ICU.
Eighty-seven (46.2%) patients were included in the Control phase and 101 (53.7%) in the Intervention phase. The median burned cutaneous surface was 20% 11%–38% and median ABSI was 7 5–9. The durations of hypnotic and opioid infusions were not statistically different between the 2 phases (8 days 2–24 vs. 6 days 2–17 (P=0.3) and 17 days 4–32 vs. 8 days 3–23 (P=0.06), respectively). The duration of mechanical ventilation was 14 days 3-29 in the Control phase and 7 days 2–24 in the Intervention phase (P=0.7). When taking into account the competition between mortality and weaning from mechanical ventilation, we found no significant difference between the 2 phases (Gray test, P=0.4). The time-series analysis showed no difference for the duration of mechanical ventilation in the Intervention phase (P=0.6). Eighteen (20.7%) patients died in the Control phase, and 18 (18%) in the Intervention phase (P=0.6).
Scale-based lightening of continuous sedation-analgesia with repeated short general anesthesia for dressing is feasible in severe burn patients but failed to demonstrate a decrease in the duration of invasive mechanical ventilation.
Context:
PCSK9 (proprotein convertase subtilisin kexin type 9) is a secreted protease that modulates cholesterol homeostasis by decreasing low-density lipoprotein receptor expression. Low levels of ...plasma lipoproteins are related to severity of illness and survival in patients of intensive care units (ICU).
Objective:
The aim of the study was to investigate the regulation of plasma PCSK9 and its association with plasma lipid parameters and clinical markers of severity during critical illness.
Design and Patients:
The plasma biobank from the previously published HYPOLYTE prospective study was used to measure PCSK9 concentrations by ELISA at days 0 and 8 in 111 patients admitted to surgical ICU for severe multiple trauma. Patients were randomly assigned to hydrocortisone therapy or placebo.
Results:
Plasma PCSK9 levels were increased by 2-fold between days 0 and 8 (231 ± 116 vs 481 ± 227 ng/ml; P = .0001). Hydrocortisone therapy did not alter PCSK9 concentrations (451 ± 216 vs 511 ± 239 ng/ml in placebo group; P = .33). PCSK9 was positively associated with low-density lipoprotein-cholesterol (Pearson coefficient, 0.26; P = .007) at day 0, but not at day 8. At day 8, an inverse correlation was found between PCSK9 and high-density lipoprotein-cholesterol (β = −653; P = .004). Although baseline PCSK9 concentrations were not associated to severity scores, PCSK9 values at day 8 were related to injury severity score (β = 6.17; P = .0007), length of stay in ICU (β = 6.14; P = .0001), and duration of both mechanical ventilation (β = 8.26; P = .0001) and norepinephrine infusion (β = 18.57; P = .015).
Conclusions:
Plasma PCSK9 appears as a late biomarker of illness severity in patients with severe multiple trauma.
Mechanical ventilation is associated with morbidity in patients with brain injury.
This study aims to assess the effectiveness of an extubation readiness bundle to decrease ventilator time in ...patients with brain injury.
Before-after design in two intensive care units (ICUs) in one university hospital. Brain-injured patients ventilated more than 24 hours were evaluated during two phases (a 3-yr control phase followed by a 22-mo intervention phase). Bundle components were protective ventilation, early enteral nutrition, standardization of antibiotherapy for hospital-acquired pneumonia, and systematic approach to extubation. The primary endpoint was the duration of mechanical ventilation.
A total of 299 and 200 patients, respectively, were analyzed in the control and the intervention phases of this before-after study. The intervention phase was associated with lower tidal volume (P < 0.01), higher positive end-expiratory pressure (P < 0.01), and higher enteral intake in the first 7 days (P = 0.01). The duration of mechanical ventilation was 14.9 ± 11.7 days in the control phase and 12.6 ± 10.3 days in the intervention phase (P = 0.02). The hazard ratio for extubation was 1.28 (95% confidence interval CI, 1.04-1.57; P = 0.02) in the intervention phase. Adjusted hazard ratio was 1.40 (95% CI, 1.12-1.76; P < 0.01) in multivariate analysis and 1.34 (95% CI, 1.03-1.74; P = 0.02) in propensity score-adjusted analysis. ICU-free days at Day 90 increased from 50 ± 33 in the control phase to 57 ± 29 in the intervention phase (P < 0.01). Mortality at Day 90 was 28.4% in the control phase and 23.5% in the intervention phase (P = 0.22).
The implementation of an evidence-based extubation readiness bundle was associated with a reduction in the duration of ventilation in patients with brain injury.
High-dose baclofen could prove beneficial in patients with unhealthy alcohol use in intensive care units (ICU). However, the pharmacokinetic properties of baclofen are unknown in this population. Our ...objectives were to investigate the pharmacokinetics of baclofen and the relationship between baclofen exposure and its toxicity in the ICU.
As part of a healthcare quality improvement project, we conducted a prospective, single-center study in a surgical intensive care unit at Nantes University Hospital in order to assess our local protocol of sedation in patients with consumption of alcohol above the recommended limits by the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Baclofen pharmacokinetics were investigated by a non-compartment analysis and a population approach in 20 patients under mechanical ventilation. After a baclofen loading dose on day 1, daily doses were divided into 3 intakes adapted to glomerular filtration rate (GFR) and blood samples were withdrawn on day 3 for pharmacokinetic analysis. Baclofen was administered until extubation or tracheostomy and agitation-related events as well as the potential side effects of baclofen were noted.
In this population, pharmacokinetic parameters absorption latency time = 0.37 h, absorption constant rate = 2.2 h−1, apparent volume of distribution = 105 L, apparent clearance (l/h) = 13.5 × (GFR/103)0.839 were characterized by modified absorption and the influence of renal function: renal failure significantly increased baclofen exposure (p = .007) and significantly decreased baclofen clearance (p = .007) compared with patients without renal failure. When comparing patients with or without possible signs of baclofen toxicity, no difference was found regarding baclofen exposure (p = .34) and plasma peak concentration (p = .26).
The a priori planned algorithm for dose adaptation according to renal clearance appeared to be suitable in our population. Daily administration of 150 mg of baclofen in ICU patients with preserved renal function did not lead to toxic concentrations in the plasma. A dose reduction of approximately 40%, 60% and 70% in patients with mild, moderate and severe renal failure could be suggested.
•Alcohol is a leading psychoactive substance responsible for one death every 12 min in France.•Baclofen use in AUD remains controversial and temporary recommendations have recently been updated with lower daily doses•In ICU, 150 mg of baclofen daily did not lead to toxic plasma concentration provided dose adjustment to renal function.
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