The COVID-19 pandemic is responsible for many hospitalizations in intensive care units (ICU), with widespread use of invasive mechanical ventilation (IMV) which exposes patients to the risk of ...ventilator-associated pneumonia (VAP). The characteristics of VAP in COVID-19 patients remain unclear.
We retrospectively collected data on all patients hospitalized for COVID-19 during the first phase of the epidemic in one of the seven ICUs of the Pays-de-Loire region (North-West France) and who were on invasive mechanical ventilation for more than 48 h. We studied the characteristics of VAP in these patients. VAP was diagnosed based on official recommendations, and we included only cases of VAP that were confirmed by a quantitative microbiological culture.
We analyzed data from 188 patients. Of these patients, 48.9% had VAP and 19.7% experienced multiple episodes. Our study showed an incidence of 39.0 VAP per 1000 days of IMV (until the first VAP episode) and an incidence of 33.7 VAP per 1000 days of IMV (including all 141 episodes of VAP). Multi-microbial VAP accounted for 39.0% of all VAP, and 205 pathogens were identified. Enterobacteria accounted for 49.8% of all the isolated pathogens. Bacteremia was associated in 15 (10.6%) cases of VAP. Pneumonia was complicated by thoracic empyema in five cases (3.5%) and by pulmonary abscess in two cases (1.4%). Males were associated with a higher risk of VAP (sHR 2.24 CI95% 1.18; 4.26 p = 0.013).
Our study showed an unusually high incidence of VAP in patients admitted to the ICU for severe COVID-19, even though our services were not inundated during the first wave of the epidemic. We also noted a significant proportion of enterobacteria. VAP-associated complications (abscess, empyema) were not exceptional.
As an observational study, this study has not been registered.
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
.
Reverse transcriptase-polymerase chain reaction (RT-PCR) testing is an important tool for diagnosing coronavirus disease 2019 (COVID-19). However, performance concerns have emerged recently, notably ...regarding sensitivity. We hypothesized that the clinical, biological, and radiological characteristics of patients with a false-negative first RT-PCR test and a final diagnosis of COVID-19 might differ from those of patients with a positive first RT-PCR test. We conducted a multicenter matched case-control study in COVID-19 patients. Patients with a negative first RT-PCR test were matched to patients with a positive first RT-PCR test on age, sex, and initial admission unit (ward or intensive care). We included 80 cases and 80 controls between March 30, and June 22, 2020. Neither mortality at hospital discharge nor hospital stay length differed between the two groups (P = 0.80 and P = 0.54, respectively). By multivariate analysis, two factors were independently associated with a lower risk of a first false-negative test, namely, headache (adjusted OR aOR, 0.07; 95% confidence interval 95% CI, 0.01-0.49; P = 0.007) and fatigue/malaise (aOR, 0.16; 95% CI, 0.03-0.81; P = 0.027); two other factors were independently associated with a higher risk of a first false-negative test, namely, platelets > 207·10
mm
(aOR, 3.81; 95% CI, 1.10-13.16; P = 0.034) and C-reactive protein > 79.8 mg·L
(aOR, 4.00; 95% CI, 1.21-13.19; P = 0.023). Patients with suspected COVID-19 whose laboratory tests indicating marked inflammation were at higher risk of a first false-negative RT-PCR test. Strategies involving serial RT-PCR testing must be rigorously evaluated.
Severe community-acquired pneumonia caused by Streptococcus pneumoniae is associated with high morbidity and mortality rates. CAL02, a novel antitoxin agent with an unprecedented mode of action, ...consists of liposomes that capture bacterial toxins known to dysregulate inflammation, cause organ damage, and impede immune defence. We aimed to assess the safety of CAL02 as an add-on therapy to antibiotics.
This randomised, double-blind, multicentre, placebo-controlled trial was done in ten intensive care units (ICUs) in France and Belgium (but only six units enrolled patients), in patients with severe community-acquired pneumococcal pneumonia who required ICU admission and had been identified as being infected with S pneumoniae. We randomly assigned participants in two stages—the first stage randomly assigned six patients (1:1) to either low-dose CAL02 or placebo, and the second stage randomly assigned 18 patients (14:4) to either high-dose CAL02 or placebo, and stratified in four blocks (4:1, 4:1, 3:1, and 3:1), in addition to standard of care. Block randomisation was done with a computer-generated random number list. Participants, investigators, other site study personnel, the sponsor, and the sponsor's designees involved in study management and monitoring were masked to the randomisation list and treatment assignment. Patients were treated with low-dose (4 mg/kg) or high-dose (16 mg/kg) CAL02 or placebo (saline), in addition to standard antibiotic therapy. Two intravenous doses of study treatment were infused, with a 24 h interval, at a concentration of 10 mg/mL, stepwise, over a maximum of 2 h on days 1 and 2. The primary objective of the study was to assess the safety and tolerability of low-dose and high-dose CAL02 in patients with severe community-acquired pneumonia treated with standard antibiotic therapy, and the primary analysis was done on the safety population (all patients who received at least one dose of the study treatment). Efficacy was a secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT02583373.
Between March 21, 2016, and Jan 13, 2018, we screened 280 patients with community-acquired pneumonia. 19 patients were enrolled and randomly assigned, resulting in 13 patients in the CAL02 groups (three assigned to low-dose CAL02 and ten assigned to high-dose CAL02) and six in the placebo group. One patient randomly assigned to placebo was allocated to the wrong treatment group and received high-dose CAL02 instead of placebo. Thus, 14 patients received CAL02 (three received low-dose CAL02 and 11 received high-dose CAL02) and five patients received placebo, constituting the safety population. At baseline, the mean APACHE II score for the total study population was 21·5 (SD 4·9; 95% CI 19·3–23·7) and 11 (58%) of 19 patients had septic shock. Adverse events occurred in 12 (86%) of 14 patients in the CAL02 treatment groups combined and all five (100%) patients in the placebo group. Serious adverse events occurred in four (29%) of 14 patients in the CAL02 treatment groups combined and two (40%) of five patients in the placebo group. One non-serious adverse event (mild increase in triglycerides) in a patient in the high-dose CAL02 group was reported as related to study drug. However, analysis of the changes in triglyceride levels in the CAL02 groups compared with the placebo group revealed no correlation with administration of CAL02. No adverse events were linked to local tolerability events. All patients, apart from one who died in the low CAL02 group (death not related to the study drug) achieved clinical cure at the test of cure visit between days 15 and 22. The sequential organ failure assessment score decreased by mean 65·0% (95% CI 50·7–79·4) in the combined CAL02 groups compared with 29·2% (12·8–45·5) in the placebo group between baseline and day 8.
The nature of adverse events was consistent with the profile of the study population and CAL02 showed a promising safety profile and tolerability. However, the difference between high-dose and low-dose CAL02 could not be assessed in this study. Efficacy was in line with the expected benefits of neutralising toxins. The results of this study support further clinical development of CAL02 and provide a solid basis for a larger clinical study.
Combioxin.
To evaluate the potential association between early dysnatremia and 6-month functional outcome after cardiac arrest.
We pooled data from four randomised clinical trials in post-cardiac-arrest ...patients admitted to the ICU with coma after stable return of spontaneous circulation (ROSC). Admission natremia was categorised as normal (135-145 mmol/L), low, or high. We analysed associations between natremia category and Cerebral Performance Category (CPC) 1 or 2 at 6 months, with and without adjustment on the modified Cardiac Arrest Hospital Prognosis Score (mCAHP).
We included 1163 patients (581 from HYPERION, 352 from TTH48, 120 from COMACARE, and 110 from Xe-HYPOTHECA) with a mean age of 63 ± 13 years and a predominance of males (72.5%). A cardiac cause was identified in 63.6% of cases. Median time from collapse to ROSC was 20 15-29 minutes. Overall, mean natremia on ICU admission was 137.5 ± 4.7 mmol/L; 211 (18.6%) and 31 (2.7%) patients had hyponatremia and hypernatremia, respectively. By univariate analysis, CPC 1 or 2 at 6 months was significantly less common in the group with hyponatremia (50/211 24% vs. 363/893 41%; P = 0.001); the mCAHP-adjusted odds ratio was 0.45 (95%CI 0.26-0.79, p = 0.005). The number of patients with hypernatremia was too small for a meaningful multivariable analysis.
Early hyponatremia was common in patients with ROSC after cardiac arrest and was associated with a poorer 6-month functional outcome. The mechanisms underlying this association remain to be elucidated in order to determine whether interventions targeting hyponatremia are worth investigating. Registration ClinicalTrial.gov, NCT01994772, November 2013, 21.
Background
Intensive care has a strong impact on health-related quality of life (HRQOL). The specific impact of cardiac arrest in non-shockable rhythm is poorly known.
Patients and methods
We ...gathered patients included in two randomized controlled trials (AWARE and HYPERION). The HYPERION trial included ICU-treated non-shockable cardiac arrest patients. The AWARE study included ICU patients requiring mechanical ventilation. We compared the 3-months HRQOL of these patients to those of a large sample of the French general population. Physical and mental dimension were compared. Multivariable linear regression was used to pick up factors associated with HRQOL.
Results
72 and 307 patients of the HYPERION and the AWARE studies were compared to 20,574 French controls. ICU patients evidenced lower scores in all the SF-36 dimensions compared to the controls. Similar scores were observed in both HYPERION and AWARe trials. The physical component score was lower in patients from the HYPERION trial compared to those from the AWARE trials and to controls (38.6 29.6-47.8, 35.4 27.5-46.4 vs. 53.0 46.0-56.7,
p
<
0.001
). After adjustment for age and gender, HYPERION and AWARE trial status were associated wit lower physical component score.
Conclusion
Health-related quality of life of unshockable cardiac arrest survivors evaluated at 3 months was similar to ICU survivors and significantly lower than in individuals from general population, especially in the physical dimensions.
While targeted temperature management (TTM) has been recommended in patients with shockable cardiac arrest (CA) and suggested in patients with non-shockable rhythms, few data exist regarding the ...impact of the rewarming rate on systemic inflammation. We compared serum levels of the proinflammatory cytokine interleukin-6 (IL6) measured with two rewarming rates after TTM at 33 °C in patients with shockable out-of-hospital cardiac arrest (OHCA).
ISOCRATE was a single-center randomized controlled trial comparing rewarming at 0.50 °C/h versus 0.25 °C/h in patients coma after shockable OHCA in 2016-2020. The primary outcome was serum IL6 level 24-48 h after reaching 33 °C. Secondary outcomes included the day-90 Cerebral Performance Category (CPC) and the 48-h serum neurofilament light-chain (NF-L) level.
We randomized 50 patients. The median IL6 area-under-the-curve was similar between the two groups (12,389 7256-37,200 vs. 8859 6825-18,088 pg/mL h; P = 0.55). No significant difference was noted in proportions of patients with favorable day-90 CPC scores (13/25 patients at 0.25 °C/h (52.0%; 95% CI 31.3-72.2%) and 13/25 patients at 0.50 °C/h (52.0%; 95% CI 31.3-72.2%; P = 0.99)). Median NF-L levels were not significantly different between the 0.25 °C/h and 0.50 °C/h groups (76.0 pg mL, 25.5-3074.0 vs. 192 pg mL, 33.6-4199.0; P = 0.43; respectively).
In our RCT, rewarming from 33 °C at 0.25 °C/h, compared to 0.50 °C/h, did not decrease the serum IL6 level after shockable CA. Further RCTs are needed to better define the optimal TTM strategy for patients with CA. Trial registration ClinicalTrials.gov, NCT02555254 . Registered September 14, 2015.
Rewarming at a rate of 0.25 °C/h, compared to 0.50 °C, did not result in lower serum IL6 levels after achievement of hypothermia at 33 °C in patients who remained comatose after shockable cardiac arrest. No associations were found between the slower rewarming rate and day-90 functional outcomes or mortality. 140-character Tweet: Rewarming at 0.25 °C versus 0.50 °C did not decrease serum IL6 levels after hypothermia at 33 °C in patients comatose after shockable cardiac arrest.
Background
Critically ill patients with obesity may have an increased risk of difficult intubation and subsequent severe hypoxemia. We hypothesized that pre-oxygenation with noninvasive ventilation ...before intubation as compared with high-flow nasal cannula oxygen may decrease the risk of severe hypoxemia in patients with obesity.
Methods
Post hoc subgroup analysis of critically ill patients with obesity (body mass index ≥ 30 kg·m
−2
) from a multicenter randomized controlled trial comparing preoxygenation with noninvasive ventilation and high-flow nasal oxygen before intubation of patients with acute hypoxemic respiratory failure (PaO
2
/FiO
2
< 300 mm Hg). The primary outcome was the occurrence of severe hypoxemia (pulse oximetry < 80%) during the intubation procedure.
Results
Among the 313 patients included in the original trial, 91 (29%) had obesity with a mean body mass index of 35 ± 5 kg·m
−2
. Patients with obesity were more likely to experience an episode of severe hypoxemia during intubation procedure than patients without obesity: 34% (31/91) vs. 22% (49/222); difference, 12%; 95% CI 1 to 23%;
P
= 0.03. Among patients with obesity, 40 received preoxygenation with noninvasive ventilation and 51 with high-flow nasal oxygen. Severe hypoxemia occurred in 15 patients (37%) with noninvasive ventilation and 16 patients (31%) with high-flow nasal oxygen (difference, 6%; 95% CI − 13 to 25%;
P
= 0.54). The lowest pulse oximetry values during intubation procedure were 87% interquartile range, 77–93 with noninvasive ventilation and 86% 78–92 with high-flow nasal oxygen (
P
= 0.98). After multivariable analysis, factors independently associated with severe hypoxemia in patients with obesity were intubation difficulty scale > 5 points and respiratory primary failure as reason for admission.
Conclusions
Patients with obesity and acute hypoxemic respiratory failure had an increased risk of severe hypoxemia during intubation procedure as compared to patients without obesity. However, preoxygenation with noninvasive ventilation may not reduce this risk compared with high-flow nasal oxygen.
Trial registration
Clinical trial number: NCT02668458 (
http://www.clinicaltrials.gov
)
Background
Few data are available about outcomes of patients screened for, but not enrolled in, randomised clinical trials.
Methods
We retrospectively reviewed patients who had non-inclusion criteria ...for the HYPERION trial comparing 33 °C to 37 °C in patients comatose after cardiac arrest in non-shockable rhythm, due to any cause. A good neurological outcome was defined as a day-90 Cerebral Performance Category score of 1 or 2.
Results
Of the 1144 patients with non-inclusion criteria, 1130 had day-90 information and, among these, 158 (14%) had good functional outcomes, compared to 7.9% overall in the HYPERION trial (10.2% with and 5.7% without hypothermia). Considerable centre-to-centre variability was found in the proportion of non-included patients who received hypothermia (0% to 83.8%) and who had good day-90 functional outcomes (0% to 31.3%). The proportion of patients with a good day-90 functional outcome was significantly higher with than without hypothermia (18.5% vs. 11.9%,
P
= 0.003).
Conclusion
Our finding of better functional outcomes without than with inclusion in the HYPERION trial, despite most non-inclusion criteria being of adverse prognostic significance (e.g., long no-flow and low-flow times and haemodynamic instability), raises important questions about the choice of patient selection criteria and the applicability of trial results to everyday practice. At present, reserving hypothermia for patients without predictors of poor prognosis seems open to criticism.
Prognostication of hypoxic-ischaemic brain injury after resuscitation from cardiac arrest is based on a multimodal approach including biomarker assays. Our goal was to assess whether plasma NSE helps ...to predict day-90 death or poor neurological outcome in patients resuscitated from cardiac arrest in non-shockable rhythm.
All included patients participated in the randomised multicentre HYPERION trial. Serum blood samples were taken 24, 48, and 72 h after randomisation; pre-treated, aliquoted, and frozen at −80 °C at the study sites; and shipped to a central biology laboratory, where the NSE assays were performed. Primary outcome was neurological status at day 90 assessed by Cerebral Performance Category (1 or 2 versus. 3, 4 or 5).
NSE was assayed in 235 assessable blood samples from 101 patients. In patients with good versus poor outcomes, median NSE values at 24, 48, and 72 h were 22.6 95%CI, 14.6;27.3 ng/mL versus 33.6 20.5;90.0 ng/mL (p < 0.04), 18.1 11.7;29.7 ng/mL versus 76.8 21.5;206.6 ng/mL (p < 0.0029), and 9 6.1;18.6 ng/mL versus 80.5 22.9;236.1 ng/mL (p < 0.001), respectively. NSE at 48 and 72 h predicted the neurological outcome with areas under the receiver-operating curve of 0.79 95%CI, 0.69;0.96 and 0.9 0.81;0.96, respectively. NSE levels did not differ significantly between the groups managed at 33°C and 37°C (p = 0.59).
Data from a multicentre trial on cardiac arrest with a non-shockable rhythm due to any cause confirm that NSE values at 72 h are associated with 90-day outcome. NSE levels did not differ significantly according to the targeted temperature.
ClinicalTrial NCT02722473.
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