Critical Care Bulletin - May 2023

 

The future of intensive care: the study of the microcirculation will help to guide our therapies

 

by J. Duranteau, D. De Backer, K. Donadello, N. I. Shapiro, S. D. Hutchings, A. Rovas, M. Legrand, A. Harrois and C. Ince 

 

Critical Care volume 27, Article number: 190 Published: 16 May 2023

 

Abstract

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.

 

Acute traumatic coma awakening by right median nerve electrical stimulation: a randomised controlled trial

Intensive Care Medicine (2023) Published: 13 May 2023

 

Purpose

Severe traumatic brain injury (TBI) leads to acute coma and may result in prolonged disorder of consciousness (pDOC). We aimed to determine whether right median nerve electrical stimulation is a safe and effective treatment for accelerating emergence from coma after TBI.

Methods

This randomised controlled trial was performed in 22 centres in China. Participants with acute coma at 7–14 days after TBI were randomly assigned (1:1) to either routine therapy and right median nerve electrical stimulation (RMNS group) or routine treatment (control group). The RMNS group received 20 mA, 300 μs, 40 Hz stimulation pulses, lasting 20 s per minutes, 8 h per day, for 2 weeks. The primary outcome was the proportion of patients who regained consciousness 6 months post-injury. The secondary endpoints were Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness scale (FOUR), Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE) scores reported as medians on day 28, 3 months and 6 months after injury, and GCS and FOUR scores on day 1 and day 7 during stimulation. Primary analyses were based on the intention-to-treat set.

Results

Between March 26, 2016, and October 18, 2020, 329 participants were recruited, of whom 167 were randomised to the RMNS group and 162 to the control group. At 6 months post-injury, a higher proportion of patients in the RMNS group regained consciousness compared with the control group (72.5%, n = 121, 95% confidence interval (CI) 65.2–78.7% vs. 56.8%, n = 92, 95% CI 49.1–64.2%, p = 0.004). GOSE at 3 months and 6 months (5 [interquartile range (IQR) 3–7] vs. 4 [IQR 2–6], p = 0.002; 6 [IQR 3–7] vs. 4 [IQR 2–7], p = 0.0005) and FOUR at 28 days (15 [IQR 13–16] vs. 13 [interquartile range (IQR) 11–16], p = 0.002) were significantly increased in the RMNS group compared with the control group. Trajectory analysis showed that significantly more patients in the RMNS group had faster GCS, CRS-R and DRS improvement (p = 0.01, 0.004 and 0.04, respectively). Adverse events were similar in both groups. No serious adverse events were associated with the stimulation device.

Conclusion

Right median nerve electrical stimulation is a possible effective treatment for patients with acute traumatic coma, that will require validation in a confirmatory trial.

 

The role of clinical phenotypes in decisions to limit life-sustaining treatment for very old patients in the ICU

 

by Oded Mousai, Lola Tafoureau, Tamar Yovell, Hans Flaatten, Bertrand Guidet, Michael Beil, Dylan de Lange, Susannah Leaver, Wojciech Szczeklik, Jesper Fjolner, Akiva Nachshon, Peter Vernon van Heerden, Leo Joskowicz, Christian Jung, Gal Hyams and Sigal Sviri 

 

Annals of Intensive Care volume 13, Article number: 40 (2023) 

 

Background

Limiting life-sustaining treatment (LST) in the intensive care unit (ICU) by withholding or withdrawing interventional therapies is considered appropriate if there is no expectation of beneficial outcome. Prognostication for very old patients is challenging due to the substantial biological and functional heterogeneity in that group. We have previously identified seven phenotypes in that cohort with distinct patterns of acute and geriatric characteristics. This study investigates the relationship between these phenotypes and decisions to limit LST in the ICU.

Methods

This study is a post hoc analysis of the prospective observational VIP2 study in patients aged 80 years or older admitted to ICUs in 22 countries. The VIP2 study documented demographic, acute and geriatric characteristics as well as organ support and decisions to limit LST in the ICU. Phenotypes were identified by clustering analysis of admission characteristics. Patients who were assigned to one of seven phenotypes (n = 1268) were analysed with regard to limitations of LST.

Results

The incidence of decisions to withhold or withdraw LST was 26.5% and 8.1%, respectively. The two phenotypes describing patients with prominent geriatric features and a phenotype representing the oldest old patients with low severity of the critical condition had the largest odds for withholding decisions. The discriminatory performance of logistic regression models in predicting limitations of LST after admission to the ICU was the best after combining phenotype, ventilatory support and country as independent variables.

Conclusions

Clinical phenotypes on ICU admission predict limitations of LST in the context of cultural norms (country). These findings can guide further research into biases and preferences involved in the decision-making about LST.

 

Antibiotic stewardship in the ICU: time to shift into overdrive

by David Mokrani, Juliette Chommeloux, Marc Pineton de Chambrun, Guillaume Hékimian and Charles-Edouard Luyt 

Annals of Intensive Care volume 13, Article number: 39 (2023)

Abstract

Antibiotic resistance is a major health problem and will be probably one of the leading causes of deaths in the coming years. One of the most effective ways to fight against resistance is to decrease antibiotic consumption. Intensive care units (ICUs) are places where antibiotics are widely prescribed, and where multidrug-resistant pathogens are frequently encountered. However, ICU physicians may have opportunities to decrease antibiotics consumption and to apply antimicrobial stewardship programs. The main measures that may be implemented include refraining from immediate prescription of antibiotics when infection is suspected (except in patients with shock, where immediate administration of antibiotics is essential); limiting empiric broad-spectrum antibiotics (including anti-MRSA antibiotics) in patients without risk factors for multidrug-resistant pathogens; switching to monotherapy instead of combination therapy and narrowing spectrum when culture and susceptibility tests results are available; limiting the use of carbapenems to extended-spectrum beta-lactamase-producing Enterobacteriaceae, and new beta-lactams to difficult-to-treat pathogen (when these news beta-lactams are the only available option); and shortening the duration of antimicrobial treatment, the use of procalcitonin being one tool to attain this goal. Antimicrobial stewardship programs should combine these measures rather than applying a single one. ICUs and ICU physicians should be at the frontline for developing antimicrobial stewardship programs.

 

Effectiveness of diaphragmatic ultrasound as a predictor of successful weaning from mechanical ventilation: a systematic review and meta-analysis

 

by Henry M. Parada-Gereda, Adriana L. Tibaduiza, Alejandro Rico-Mendoza, Daniel Molano-Franco, Victor H. Nieto, Wanderley A. Arias-Ortiz, Purificación Perez-Terán and Joan R. Masclans 

 

Critical Care volume 27, Article number: 174 (2023) 

 

Background

Several measurements have been used to predict the success of weaning from mechanical ventilation; however, their efficacy varies in different studies. In recent years, diaphragmatic ultrasound has been used for this purpose. We conducted a systematic review and meta-analysis to evaluate the effectiveness of diaphragmatic ultrasound in predicting the success of weaning from mechanical ventilation.

Methods

Two investigators independently searched PUBMED, TRIP, EMBASE, COCHRANE, SCIENCE DIRECT, and LILACS for articles published between January 2016 and July 2022. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool; additionally, the certainty of the evidence is evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. Sensitivity and specificity analysis was performed for diaphragmatic excursion and diaphragmatic thickening fraction; positive and negative likelihood ratios and diagnostic odds ratios (DOR) with their confidence intervals (95% CI) were calculated by random effects analysis, summary receiver operating characteristic curve was estimated. Sources of heterogeneity were explored by subgroup analysis and bivariate meta-regression.

Results

Twenty-six studies were included, of which 19 were included in the meta-analysis (1204 patients). For diaphragmatic excursion, sensitivity was 0.80 (95% CI 0.77–0.83), specificity 0.80 (95% CI 0.75–0.84), area under the summary receiver operating characteristic curve 0.87 and DOR 17.1 (95% CI 10.2–28.6). For the thickening fraction, sensitivity was 0.85 (95% CI 0.82–0.87), specificity 0.75 (95% CI 0.69–0.80), area under the summary receiver operating characteristic curve 0.87 and DOR 17.2 (95% CI 9.16–32.3). There was heterogeneity among the included studies. When performing a subgroup analysis and excluding studies with atypical cutoff values, sensitivity and specificity increased for diaphragmatic thickening fraction; sensitivity increased and specificity decreased for diaphragmatic excursion; when comparing studies using pressure support (PS) versus T-tube, there was no significant difference in sensitivity and specificity; bivariate meta-regression analysis shows that patient position at the time of testing was a factor of heterogeneity in the included studies.

Conclusions

Measurement of diaphragmatic excursion and diaphragmatic thickening fraction predict the probability of successful weaning from mechanical ventilation with satisfactory diagnostic accuracy; however, significant heterogeneity was evident in the different included studies. Studies of high methodological quality in specific subgroups of patients in intensive care units are needed to evaluate the role of diaphragmatic ultrasound as a predictor of weaning from mechanical ventilation.

 

Optimizing enteral nutrition delivery by implementing volume-based feeding protocol for critically ill patients: an updated meta-analysis and systematic review

 

by Lu Wang, Yu Wang, Hua-Xin Li, Rui-peng Zhang, Li Chang, Jun Zeng and Hua Jiang 

 

Critical Care volume 27, Article number: 173 (2023) 

 

Background

This study aims to provide an updated assessment of the efficacy of optimized enteral nutrition (EN) delivery by implementing the volume-based feeding (VBF) protocol in critically ill patients.

Methods

We updated our previous literature retrieval with no language restrictions. The inclusion criteria were:1) Participants: Critically ill patients (Patients who was admitted in ICU; 2) Intervention: The VBF protocol was adopted for EN administration; 3) Comparison: The rate-based feeding (RBF) protocol was adopted for EN administration; 4) Major outcomes: EN nutrition delivery. The exclusion criteria included participants aged < 18 years, duplicated literature, animal and cellular experiments, and studies lacking any of the outcomes mentioned in the inclusion criteria. The databases included MEDLINE (through PubMed), Web of Science, Cochrane Library, Chinese Biomedical Literature Service System (SinoMed), Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure.

Result

Sixteen studies involving a total of 2896 critically ill patients are included in the updated meta-analysis. Compared with the previous meta-analysis, nine new studies were added that included 2205 more patients. The VBF protocol significantly improved energy (MD = 15.41%, 95% CI: [10.68, 20.14], p < 0.00001) and protein (MD = 22.05%, 95% CI: [10.89, 33.22], p = 0.0001) delivery. The patients in the VBF group stayed in the ICU for a shorter time (MD = 0.78, 95% CI: [0.01, 1.56], p = 0.05). The VBF protocol did not increase the risk of death (RR = 1.03, 95% CI: [0.85, 1.24], p = 0.76) or prolong the mechanical ventilation duration (MD = 0.81, 95% CI: [-0.30,1.92], p = 0.15). In addition, the VBF protocol did not affect EN complications, such as diarrhea (RR = 0.91, 95% CI: [0.73, 1.15], p = 0.43), emesis (RR = 1.23, 95% CI: [0.76, 1.99], p = 0.41), feeding intolerance (RR = 1.14, 95% CI: [0.63, 2.09], p = 0.66), and gastric retention (RR = 0.45, 95% CI: [0.16, 1.30], p = 0.14).

Conclusion

Our study revealed that the VBF protocol significantly improved calorie and protein delivery in critically ill patients with no additional risk.

 

Heterogeneity in the definition of delirium in ICUs and association with the intervention effect in randomized controlled trials: a meta-epidemiological study

 

by Lucie Collet, Aymeric Lanore, Camille Alaterre, Jean-Michel Constantin, Guillaume L. Martin, Agnès Caille, Arthur James and Agnès Dechartres 

 

Critical Care volume 27, Article number: 170 (2023)

 

Purpose

To evaluate the heterogeneity in the definition of delirium in randomized controlled trials (RCTs) included in meta-analyses of delirium in intensive care units (ICUs) and to explore whether intervention effect depends on the definition used.

Methods

We searched PubMed for meta-analyses including RCTs evaluating prevention or treatment strategies of delirium in ICU. The definition of delirium was collected from RCTs and classified as validated (DSM criteria, CAM-ICU, ICDSC, NEECHAM, DRS-R98) or non-validated (non-validated scales, set of symptoms, physician appreciation or not reported). We conducted a meta-epidemiological analysis to compare intervention effects between trials using or not a validated definition by a two-step method as primary analysis and a multilevel model as secondary analysis. A ratio of odds ratios (ROR) < 1 indicated larger intervention effects in trials using a non-validated definition.

Results

Of 149 RCTs (41 meta-analyses), 109 (73.1%) used a validated definition and 40 (26.8%) did not (including 31 [20.8%] not reporting the definition). The primary analysis of 7 meta-analyses (30 RCTs) found no significant difference in intervention effects between trials using a validated definition and the others (ROR = 0.54, 95% CI 0.27–1.08), whereas the secondary multilevel analysis including 12 meta-analyses (67 RCTs) found significantly larger effects for trials using a non-validated versus a validated definition (ROR = 0.36, 95% CI 0.21–0.62).

Conclusion

The definition of delirium was heterogeneous across RCTs, with one-fifth not reporting how they evaluated delirium. We did not find a significant association with intervention effect in the primary analysis. The secondary analysis including more studies revealed significantly larger intervention effects in trials using a non-validated versus a validated definition.

 Expert consensus statement on venovenous extracorporeal membrane oxygenation ECMO for COVID-19 severe ARDS: an international Delphi study

by Ahmed A. Rabie, Alyaa Elhazmi, Mohamed H. Azzam, Akram Abdelbary, Ahmed Labib, Alain Combes, Bishoy Zakhary, Graeme MacLaren, Ryan P. Barbaro, Giles J. Peek, Marta Velia Antonini, Kiran Shekar, Abdulrahman Al‐Fares, Pranay Oza, Yatin Mehta, Huda Alfoudri

Annals of Intensive Care volume 13, Article number: 36 (2023)

 

Background

The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus.

Objectives

To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS.

Methods

The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel’s questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively.

Results

In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics.

Conclusion

Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations.

 

Optimization of polymyxin B regimens for the treatment of carbapenem-resistant organism nosocomial pneumonia: a real-world prospective study

 

by Tiantian Tang, Ying Li, Ping Xu, Yanjun Zhong, Min Yang, Wanjun Ma, Daxiong Xiang, Bikui Zhang and Yangang Zhou 

 

Critical Care volume 27, Article number: 164 (2023)

 

Background

Polymyxin B is the first-line therapy for Carbapenem-resistant organism (CRO) nosocomial pneumonia. However, clinical data for its pharmacokinetic/pharmacodynamic (PK/PD) relationship are limited. This study aimed to investigate the relationship between polymyxin B exposure and efficacy for the treatment of CRO pneumonia in critically ill patients, and to optimize the individual dosing regimens.

Methods

Patients treated with polymyxin B for CRO pneumonia were enrolled. Blood samples were assayed using a validated high-performance liquid chromatography-tandem mass spectrometry method. Population PK analysis and Monte Carlo simulation were performed using Phoenix NLME software. Logistic regression analyses and receiver operating characteristic (ROC) curve were employed to identify the significant predictors and PK/PD indices of polymyxin B efficacy.

Results

A total of 105 patients were included, and the population PK model was developed based on 295 plasma concentrations. AUCss,24 h/MIC (AOR = 0.97, 95% CI 0.95–0.99, p = 0.009), daily dose (AOR = 0.98, 95% CI 0.97–0.99, p = 0.028), and combination of inhaled polymyxin B (AOR = 0.32, 95% CI 0.11–0.94, p = 0.039) were independent risk factors for polymyxin B efficacy. ROC curve showed that AUCss,24 h/MIC is the most predictive PK/PD index of polymyxin B for the treatment of nosocomial pneumonia caused by CRO, and the optimal cutoff point value was 66.9 in patients receiving combination therapy with another antimicrobial. Model-based simulation suggests that the maintaining daily dose of 75 and 100 mg Q12 h could achieve ≥ 90% PTA of this clinical target at MIC values ≤ 0.5 and 1 mg/L, respectively. For patients unable to achieve the target concentration by intravenous administration, adjunctive inhalation of polymyxin B would be beneficial.

Conclusions

For CRO pneumonia, daily dose of 75 and 100 mg Q12 h was recommended for clinical efficacy. Inhalation of polymyxin B is beneficial for patients who cannot achieve the target concentration by intravenous administration.

 

Necrotizing soft tissue infections in critically ill neutropenic patients: a French multicentre retrospective cohort study

 

by Romain Arrestier, Anis Chaba, Asma Mabrouki, Clément Saccheri, Emmanuel Canet, Marc Pineton de Chambrun, Annabelle Stoclin, Muriel Picard, Florent Wallet, François Perier, Matthieu Turpin, Laurent Argaud, Maxens Decavèle, Nahéma Issa, Cyril Cadoz, Kada Klouche

 

Annals of Intensive Care volume 13, Article number: 34 (2023) 

 

Background

Necrotizing soft tissue infections (NSTIs) are rare life-threatening bacterial infections. Few data are available regarding neutropenic patients with NSTIs. Our objectives were to describe the characteristics and management of neutropenic patients with NSTIs in intensive care units (ICUs). We conducted a retrospective multicentre cohort study in 18 ICUs between 2011 and 2021. Patients admitted with NSTIs and concomitant neutropenia at diagnosis were included and compared to non-neutropenic patients with NSTIs. The relationship between therapeutic interventions and outcomes was assessed using Cox regression and propensity score matching.

Results

76 neutropenic patients were included and compared to 165 non-neutropenic patients. Neutropenic patients were younger (54 ± 14 vs 60 ± 13 years, p = 0.002) and had less lower limb (44.7% vs 70.9%, p < 0.001) and more abdomino-perineal NSTIs (43.4% vs 18.8%, p < 0.001). Enterobacterales and non-fermenting gram-negative bacteria were the most frequently isolated microorganisms in neutropenic patients. In-hospital mortality was significantly higher in neutropenic than in non-neutropenic patients (57.9% vs 28.5%, p < 0.001). Granulocyte colony-stimulating factor (G-CSF) administration was associated with a lower risk of in-hospital mortality in univariable Cox (hazard ratio (HR) = 0.43 95% confidence interval (CI) [0.23–0.82], p = 0.010) and multivariable Cox (adjusted HR = 0.46 95% CI [0.22–0.94], p = 0.033) analyses and after overlap propensity score weighting (odds ratio = 0.25 95% CI [0.09; 0.68], p = 0.006).

Conclusions

Critically ill neutropenic patients with NSTIs present different clinical and microbiological characteristics and are associated with a higher hospital mortality than non-neutropenic patients. G-CSF administration was associated with hospital survival.

 

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study

Critical Care Medicine, April 20, 2023

Objectives: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF.

Design: Multicenter, prospective, inception cohort study.

Setting: Forty-four ICUs in 12 countries in four geographical regions.

Subjects: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021.

Interventions: None.

Measurements and Main Results: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8–17.6), of which newly developed AF was 13.3% (11.5–15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16–23), magnesium 16% (13–20), potassium 15% (12–19), amiodarone 51% (47–55), beta-1 selective blockers 34% (30–38), calcium channel blockers 4% (2–6), digoxin 16% (12–19), and direct current cardioversion in 4% (2–6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95–1.99).

Conclusions: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.