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Breast Surgery

Tuesday 21 May 2024

Critical Care bulletin - May 2024

 

Development and validation of the tic score for early detection of traumatic coagulopathy upon hospital admission: a cohort study

 by Louis Brac, Albrice Levrat, Charles-Hervé Vacheron, Pierre Bouzat, Tristan Delory and Jean-Stéphane David 

 Critical Care volume 28, Article number: 168, Published: 18 May 2024

 Background

Critically injured patients need rapid and appropriate hemostatic treatment, which requires prompt identification of trauma-induced coagulopathy (TIC) upon hospital admission. We developed and validated the performance of a clinical score based on prehospital resuscitation parameters and vital signs at hospital admission for early diagnosis of TIC.

Methods

The score was derived from a level-1 trauma center registry (training set). It was then validated on data from two other level-1 trauma centers: first on a trauma registry (retrospective validation set), and then on a prospective cohort (prospective validation set). TIC was defined as a PTratio > 1.2 at hospital admission. Prehospital (vital signs and resuscitation care) and admission data (vital signs and laboratory parameters) were collected. We considered parameters independently associated with TIC in the score (binomial logistic regression). We estimated the score’s performance for the prediction of TIC.

Results

A total of 3489 patients were included, and among these a TIC was observed in 22% (95% CI 21–24%) of cases. Five criteria were identified and included in the TIC Score: Glasgow coma scale < 9, Shock Index > 0.9, hemoglobin < 11 g.dL−1, prehospital fluid volume > 1000 ml, and prehospital use of norepinephrine (yes/no). The score, ranging from 0 and 9 points, had good performance for the identification of TIC (AUC: 0.82, 95% CI: 0.81–0.84) without differences between the three sets used. A score value < 2 had a negative predictive value of 93% and was selected to rule-out TIC. Conversely, a score value ≥ 6 had a positive predictive value of 92% and was selected to indicate TIC.

Conclusion

The TIC Score is quick and easy to calculate and can accurately identify patients with TIC upon hospital admission.

 

Oral challenge vs routine care to assess low-risk penicillin allergy in critically ill hospital patients (ORACLE): a pilot safety and feasibility randomised controlled trial

 

Intensive Care Medicine: Published 13 May 2024

Purpose

Critically ill patients are vulnerable to penicillin allergy labels that may be incorrect. The validity of skin testing in intensive care units (ICUs) is uncertain. Many penicillin allergy labels are low risk, and validated tools exist to identify those amenable to direct oral challenge. This pilot randomised controlled trial explored the feasibility, safety, and validity of direct enteral challenge for low-risk penicillin allergy labels in critical illness.

Methods

Consenting patients with a low-risk penicillin allergy label (PAL) (PEN-FAST risk assessment score < 3) in four ICUs (Melbourne, Australia) were randomised 1:1 to penicillin (250 mg amoxicillin or implicated penicillin) direct enteral challenge versus routine care (2-h post-randomisation observation for each arm). Repeat challenge was performed post -ICU in the intervention arm. Patients were reviewed at 24 h and 5 days after each challenge/observation.

Results

We screened 533 patients. 130 (24.4%) were eligible and 80/130 (61.5%) enrolled (age median 64.5 years (interquartile range, IQR 53.5, 74), PEN-FAST median 1 (IQR 0,1)), with 40 (50%) randomised to direct enteral challenge. A positive challenge rate of 2.5% was identified. No antibiotic-associated serious adverse events were identified. 32/40 (80%) received a repeat challenge (zero positive). Post-randomisation, 13 (32%) of the intervention arm and 4 (10%) of the control arm received penicillin (odds ratio, OR 4.33 [1.27, 14.78] p = 0.019).

Conclusion

These findings support the safety, validity, and feasibility of direct enteral challenge for critically ill patients with PEN-FAST assessed low-risk penicillin allergy. The absence of false negative results was confirmed by subsequent negative repeat challenges. A relatively low recruitment to screened ratio suggests that more inclusive eligibility criteria and integration of allergy assessment into routine ICU processes are needed to optimise allergy delabelling in critical illness.

 

Incidence, risk factors and outcomes of nosocomial infection in adult patients supported by extracorporeal membrane oxygenation: a systematic review and meta-analysis

 by Ali Ait Hssain, Amir Vahedian-Azimi, Abdulsalam Saif Ibrahim, Ibrahim Fawzy Hassan, Elie Azoulay and Michael Darmon 

 Critical Care volume 28, Article number: 158, Published: 10 May 2024

Background

An increasing number of patients requires extracorporeal membrane oxygenation (ECMO) for life support. This supportive modality is associated with nosocomial infections (NIs). This systematic review and meta-analysis aim to assess the incidence and risk factors of NIs in adult.

Methods

We searched PubMed, Scopus, Web of Science, and ProQuest databases up to 2022. The primary endpoint was incidence of NI. Secondary endpoints included time to infection, source of infection, ECMO duration, Intensive care and hospital length of stay (LOS), ECMO survival and overall survival. Incidence of NI was reported as pooled proportions and 95% confidence intervals (CIs), while dichotomous outcomes were presented as risk ratios (RR) as the effective index and 95% CIs using a random-effects model.

Results

Among the 4,733 adult patients who received ECMO support in the 30 included studies, 1,249 ECMO-related NIs per 1000 ECMO-days was observed. The pooled incidence of NIs across 18 studies involving 3424 patients was 26% (95% CI 14–38%).Ventilator-associated pneumonia (VAP) and bloodstream infections (BSI) were the most common NI sources. Infected patients had lower ECMO survival and overall survival rates compared to non-infected patients, with risk ratio values of 0.84 (95% CI 0.74–0.96, P = 0.01) and 0.80 (95% CI 0.71–0.90, P < 0.001), respectively.

Conclusion

Results showed that 16% and 20% lower of ECMO survival and overall survival in patients with NI than patients without NI, respectively. However, NI increased the risk of in-hospital mortality by 37% in infected patients compared with non-infected patients. In addition, this study identified the significant positive correlation between ECMO duration and ECMO-related NI.

 

Effect of immediate initiation of invasive ventilation on mortality in acute hypoxemic respiratory failure: a target trial emulation

by Ricard Mellado-Artigas, Xavier Borrat, Bruno L. Ferreyro, Christopher Yarnell, Sicheng Hao, Kerollos N. Wanis, Enric Barbeta, Antoni Torres, Carlos Ferrando and Laurent Brochard 

Critical Care volume 28, Article number: 157, Published: 10 May 2024

Purpose

Invasive ventilation is a fundamental treatment in intensive care but its precise timing is difficult to determine. This study aims at assessing the effect of initiating invasive ventilation versus waiting, in patients with hypoxemic respiratory failure without immediate reason for intubation on one-year mortality.

Methods

Emulation of a target trial to estimate the benefit of immediately initiating invasive ventilation in hypoxemic respiratory failure, versus waiting, among patients within the first 48-h of hypoxemia. The eligible population included non-intubated patients with SpO2/FiO2 ≤ 200 and SpO2 ≤ 97%. The target trial was emulated using a single-center database (MIMIC-IV) which contains granular information about clinical status. The hourly probability to receive mechanical ventilation was continuously estimated. The hazard ratios for the primary outcome, one-year mortality, and the secondary outcome, 30-day mortality, were estimated using weighted Cox models with stabilized inverse probability weights used to adjust for measured confounding.

Results

2996 Patients fulfilled the inclusion criteria of whom 792 were intubated within 48 h. Among the non-invasive support devices, the use of oxygen through facemask was the most common (75%). Compared to patients with the same probability of intubation but who were not intubated, intubation decreased the hazard of dying for the first year after ICU admission HR 0.81 (95% CI 0.68–0.96, p = 0.018). Intubation was associated with a 30-day mortality HR of 0.80 (95% CI 0.64–0.99, p = 0.046).

Conclusion

The initiation of mechanical ventilation in patients with acute hypoxemic respiratory failure reduced the hazard of dying in this emulation of a target trial.

 

Effects of non-invasive respiratory support in post-operative patients: a systematic review and network meta-analysis

by Tommaso Pettenuzzo, Annalisa Boscolo, Elisa Pistollato, Chiara Pretto, Tommaso Antonio Giacon, Sara Frasson, Francesco Maria Carbotti, Francesca Medici, Giovanni Pettenon, Giuliana Carofiglio, Marco Nardelli, Nicolas Cucci, Clara Letizia Tuccio, Veronica Gagliardi, Chiara Schiavolin, Caterina Simoni… 

Critical Care volume 28, Article number: 152, Published: 08 May 2024

Background

Re-intubation secondary to post-extubation respiratory failure in post-operative patients is associated with increased patient morbidity and mortality. Non-invasive respiratory support (NRS) alternative to conventional oxygen therapy (COT), i.e., high-flow nasal oxygen, continuous positive airway pressure, and non-invasive ventilation (NIV), has been proposed to prevent or treat post-extubation respiratory failure. Aim of the present study is assessing the effects of NRS application, compared to COT, on the re-intubation rate (primary outcome), and time to re-intubation, incidence of nosocomial pneumonia, patient discomfort, intensive care unit (ICU) and hospital length of stay, and mortality (secondary outcomes) in adult patients extubated after surgery.

Methods

A systematic review and network meta-analysis of randomized and non-randomized controlled trials. A search from Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science from inception until February 2, 2024 was performed.

Results

Thirty-three studies (11,292 patients) were included. Among all NRS modalities, only NIV reduced the re-intubation rate, compared to COT (odds ratio 0.49, 95% confidence interval 0.28; 0.87, p = 0.015, I2 = 60.5%, low certainty of evidence). In particular, this effect was observed in patients receiving NIV for treatment, while not for prevention, of post-extubation respiratory failure, and in patients at high, while not low, risk of post-extubation respiratory failure. NIV reduced the rate of nosocomial pneumonia, ICU length of stay, and ICU, hospital, and long-term mortality, while not worsening patient discomfort.

Conclusions

In post-operative patients receiving NRS after extubation, NIV reduced the rate of re-intubation, compared to COT, when used for treatment of post-extubation respiratory failure and in patients at high risk of post-extubation respiratory failure.

 

Hospital-acquired bloodstream infections in critically ill cirrhotic patients: a post-hoc analysis of the EUROBACT-2 international cohort study

 

by Hannah Wozniak, Alexis Tabah, François Barbier, Stéphane Ruckly, Ambre Loiodice, Murat Akova, Marc Leone, Andrew Conway Morris, Matteo Bassetti, Kostoula Arvaniti, Ricard Ferrer, Liesbet de Bus, Jose Artur Paiva, Hendrik Bracht, Adam Mikstacki, Adel Alsisi

 

Annals of Intensive Care volume 14, Article number: 70 Published: 02 May 2024

 

Background

Hospital-acquired bloodstream infections are common in the intensive care unit (ICU) and have a high mortality rate. Patients with cirrhosis are especially susceptible to infections, yet there is a knowledge gap in the epidemiological distinctions in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients in the ICU. It has been suggested that cirrhotic patients, present a trend towards more gram-positive infections, and especially enterococcal infections. This study aims to describe epidemiological differences in hospital-acquired bloodstream infections between cirrhotic and non-cirrhotic patients hospitalized in the ICU regarding infection sources, microorganisms and mortality.

Methods

Using prospective Eurobact-2 international cohort study data, we compared hospital-acquired bloodstream infections sources and microorganisms in cirrhotic and non-cirrhotic patients. The association between Enterococcus faecium and cirrhosis was studied using a multivariable mixed logistic regression. The association between cirrhosis and mortality was assessed by a multivariable frailty Cox model.

Results

Among the 1059 hospital-acquired bloodstream infections patients included from 101 centers, 160 had cirrhosis. Hospital-acquired bloodstream infection source in cirrhotic patients was primarily abdominal (35.6%), while it was pulmonary (18.9%) for non-cirrhotic (p < 0.01). Gram-positive hospital-acquired bloodstream infections accounted for 42.3% in cirrhotic patients compared to 33.2% in non-cirrhotic patients (p = 0.02). Hospital-acquired bloodstream infections in cirrhotic patients were most frequently caused by Klebsiella spp (16.5%), coagulase-negative Staphylococci (13.7%) and E. faecium (11.5%). E. faecium bacteremia was more frequent in cirrhotic patients (11.5% versus 4.5%, p < 0.01). After adjusting for possible confounding factors, cirrhosis was associated with higher E. faecium hospital-acquired bloodstream infections risk (Odds ratio 2.5, 95% CI 1.3–4.5, p < 0.01). Cirrhotic patients had increased mortality compared to non-cirrhotic patients (Hazard Ratio 1.3, 95% CI 1.01–1.7, p = 0.045).

Conclusions

Critically ill cirrhotic patients with hospital-acquired bloodstream infections exhibit distinct epidemiology, with more Gram-positive infections and particularly Enterococcus faecium.

 

Low Versus High Blood Pressure Targets in Critically Ill and Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

 by D’Amico, Filippo; Pruna, Alessandro; Putowski, Zbigniew; Dormio, Sara; Ajello, Silvia; Scandroglio, Anna Mara; Lee, Todd C.; Zangrillo, Alberto; Landoni, Giovanni 

 Critical Care Medicine, April 24, 2024.

 Objectives: 

Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality.

Data Sources: 

We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024.

Study Selection: 

Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings.

Data Extraction: 

The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928.

Data Synthesis: 

Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients. Patients in the low blood pressure target group had lower mortality (23 studies included: 1019/7679 [13.3%] vs. 1103/7649 [14.4%]; relative risk 0.93; 95% CI, 0.87–0.99; p = 0.03; I2 = 0%). This corresponded to a 97.4% probability of any increase in mortality with a Bayesian approach. These findings were mainly driven by studies performed in the ICU setting and with treatment lasting more than 24 hours; however, the magnitude and direction of the results were similar in the majority of sensitivity analyses including the analysis restricted to low risk of bias studies. We also observed a lower rate of atrial fibrillation and fewer patients requiring transfusion in low-pressure target groups. No differences were found in the other secondary outcomes.

Conclusions: 

Based on pooled randomized trial evidence, a lower compared with a higher blood pressure target results in a reduction of mortality, atrial fibrillation, and transfusion requirements. Lower blood pressure targets may be beneficial but there is ongoing uncertainty. However, the present meta-analysis does not confirm previous findings and recommendations. These results might inform future guidelines and promote the study of the concept of protective hemodynamics.

 

Efficacy and safety of antibiotics targeting Gram-negative bacteria in nosocomial pneumonia: a systematic review and Bayesian network meta-analysis

 by David Luque Paz, Dara Chean, Pierre Tattevin, Damien Luque Paz, Betsega Assefa Bayeh, Achille Kouatchet, Delphine Douillet and Jérémie Riou

 Annals of Intensive Care volume 14, Article number: 66, Published: 25 April 2024

Background

Multiple randomized controlled studies have compared numerous antibiotic regimens, including new, recently commercialized antibiotics in the treatment of nosocomial pneumonia (NP). The objective of this Bayesian network meta-analysis (NMA) was to compare the efficacy and the safety of different antibiotic treatments for NP.

Methods

We conducted a systematic search of PubMed, Medline, Web of Science, EMBASE and the Cochrane Library databases from 2000 through 2021. The study selection included studies comparing antibiotics targeting Gram-negative bacilli in the setting of NP. The primary endpoint was 28 day mortality. Secondary outcomes were clinical cure, microbiological cure and adverse events.

Results

Sixteen studies encompassing 4993 patients were included in this analysis comparing 13 antibiotic regimens. The level of evidence for mortality comparisons ranged from very low to moderate. No significant difference in 28 day mortality was found among all beta-lactam regimens. Only the combination of meropenem plus aerosolized colistin was associated with a significant decrease of mortality compared to using intravenous colistin alone (OR = 0.43; 95% credible interval [0.17–0.94]), based on the results of the smallest trial included. The clinical failure rate of ceftazidime was higher than meropenem with (OR = 1.97; 95% CrI [1.19–3.45]) or without aerosolized colistin (OR = 1.40; 95% CrI [1.00–2.01]), imipemen/cilastatin/relebactam (OR = 1.74; 95% CrI [1.03–2.90]) and ceftazidime/avibactam (OR = 1.48; 95% CrI [1.02–2.20]). For microbiological cure, no substantial difference between regimens was found, but ceftolozane/tazobactam had the highest probability of being superior to comparators. In safety analyses, there was no significant difference between treatments for the occurrence of adverse events, but acute kidney failure was more common in patients receiving intravenous colistin.

Conclusions

This network meta-analysis suggests that most antibiotic regimens, including new combinations and cefiderocol, have similar efficacy and safety in treating susceptible Gram-negative bacilli in NP. Further studies are necessary for NP caused by multidrug-resistant bacteria.

Registration PROSPERO CRD42021226603

 

Respiratory drive heterogeneity associated with systemic inflammation and vascular permeability in acute respiratory distress syndrome

 by Elias Baedorf-Kassis, Michael Murn, Amy L. Dzierba, Alexis L. Serra, Ivan Garcia, Emily Minus, Clarissa Padilla, Todd Sarge, Valerie M. Goodspeed, Michael A. Matthay, Michelle N. Gong, Deborah Cook, Stephen H. Loring, Daniel Talmor and Jeremy R. Beitler 

 Critical Care volume 28, Article number: 136, Published: 23 April 2024

Background

In acute respiratory distress syndrome (ARDS), respiratory drive often differs among patients with similar clinical characteristics. Readily observable factors like acid–base state, oxygenation, mechanics, and sedation depth do not fully explain drive heterogeneity. This study evaluated the relationship of systemic inflammation and vascular permeability markers with respiratory drive and clinical outcomes in ARDS.

Methods

ARDS patients enrolled in the multicenter EPVent-2 trial with requisite data and plasma biomarkers were included. Neuromuscular blockade recipients were excluded. Respiratory drive was measured as PES0.1, the change in esophageal pressure during the first 0.1 s of inspiratory effort. Plasma angiopoietin-2, interleukin-6, and interleukin-8 were measured concomitantly, and 60-day clinical outcomes evaluated.

Results

54.8% of 124 included patients had detectable respiratory drive (PES0.1 range of 0–5.1 cm H2O). Angiopoietin-2 and interleukin-8, but not interleukin-6, were associated with respiratory drive independently of acid–base, oxygenation, respiratory mechanics, and sedation depth. Sedation depth was not significantly associated with PES0.1 in an unadjusted model, or after adjusting for mechanics and chemoreceptor input. However, upon adding angiopoietin-2, interleukin-6, or interleukin-8 to models, lighter sedation was significantly associated with higher PES0.1. Risk of death was less with moderate drive (PES0.1 of 0.5–2.9 cm H2O) compared to either lower drive (hazard ratio 1.58, 95% CI 0.82–3.05) or higher drive (2.63, 95% CI 1.21–5.70) (p = 0.049).

Conclusions

Among patients with ARDS, systemic inflammatory and vascular permeability markers were independently associated with higher respiratory drive. The heterogeneous response of respiratory drive to varying sedation depth may be explained in part by differences in inflammation and vascular permeability.

 

Rapidly improving ARDS differs clinically and biologically from persistent ARDS

 

by Patricia L. Valda Toro, Andrew Willmore, Nelson E. Wu, Kevin L. Delucchi, Alejandra Jauregui, Pratik Sinha, Kathleen D. Liu, Carolyn M. Hendrickson, Aartik Sarma, Lucile P. A. Neyton, Aleksandra Leligdowicz, Charles R. Langelier, Hanjing Zhuo, Chayse Jones, Kirsten N. Kangelaris, Antonio D. Gomez

 

Critical Care volume 28, Article number: 132 Published: 22 April 2024

 

Background

Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes.

Methods

We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO2:FiO2 > 300 or (ii) SpO2: FiO2 > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described.

Results

RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001).

Conclusions

This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials.