Other bulletins in this series include:

Breast Surgery

Thursday 23 January 2020

Timing of Tracheostomy in Pediatric Patients: A Systematic Review and Meta-Analysis*



by Abdelaal Ahmed Mahmoud M. Alkhatip, Ahmed; Younis, Mohamed; Jamshidi, Negar; Hussein, Hazem A; Farag, Ehab; Hamza, Mohamed K.; Bahr, Mahmoud H.; Goda Ahmed, Ahmed; Sallam, Amr M.; Mohamed, Hassan; Elayashy, Mohamed; Hosny, Hisham; Yassin, Hany M.; Abdelhaq, Mohamed; Elramely, Mohamed A.; Reeves, David; Mills, Kerry E.; Kamal, Ahmed M.; Zakaria, Dina


Objectives: Tracheostomy is a very common clinical intervention in critically ill adult patients. The indications for tracheostomy procedures in pediatric patients with complex conditions have increased dramatically in recent years, but there are currently no guidelines on the optimal timing of tracheostomy in pediatric patients undergoing prolonged ventilation.
 Data Sources: We performed a systematic search of the existing literature in MEDLINE via PubMed and Embase databases and the Cochrane Library to identify clinical trials, observational studies, and cohort studies that compare early and late tracheostomy in children. The date of the last search was August 27, 2018. Included articles were subjected to manual searching.
Study Selection: Studies in mechanically ventilated children that compared early with late tracheostomy were included.
Data Extraction: Data were extracted into a spreadsheet and copied into Review Manager 5.3 (The Cochrane Collaboration, Copenhagen, Denmark).
Data Synthesis: Data were meta-analyzed using an inverse variance, random effects model. Continuous outcomes were calculated as mean differences with 95% CIs, and dichotomous outcomes were calculated as Mantel-Haenszel risk ratios with 95% CIs. We included eight studies (10 study arms). These studies were all retrospective cohort studies. Early tracheostomy was associated with significant reductions in mortality, days on mechanical ventilation, and length of intensive care and total hospital stay, although the lack of randomized, controlled trials limits the validity of these findings. Although variance was imputed for some studies, these conclusions did not change after removing these studies from the analysis.
Conclusions: In children on mechanical ventilation, early tracheostomy may improve important medical outcomes. However, our data demonstrate the urgent need for high-quality, randomized controlled trials in the pediatric population.

Vasopressin and its analogues in shock states: a review



by Julien Demiselle, Nicolas Fage, Peter Radermacher and Pierre Asfar

Annals of Intensive Care volume 10, Article number: 9 (2020) Published: 22 January 2020

Abstract
Activation of arginine–vasopressin is one of the hormonal responses to face vasodilation-related hypotension. Released from the post-pituitary gland, vasopressin induces vasoconstriction through the activation of V1a receptors located on vascular smooth muscle cells. Due to its non-selective receptor affinity arginine–vasopressin also activates V2 (located on renal tubular cells of collecting ducts) and V1b (located in the anterior pituitary and in the pancreas) receptors, thereby potentially promoting undesired side effects such as anti-diuresis, procoagulant properties due to release of the von Willebrand’s factor and platelet activation. Finally, it also cross-activates oxytocin receptors. During septic shock, vasopressin plasma levels were reported to be lower than expected, and a hypersensitivity to its vasopressor effect is reported in such situation. Terlipressin and selepressin are synthetic vasopressin analogues with a higher affinity for the V1 receptor, and, hence, potentially less side effects. In this narrative review, we present the current knowledge of the rationale, benefits and risks of vasopressin use in the setting of septic shock and vasoplegic shock following cardiac surgery. Clearly, vasopressin administration allows reducing norepinephrine requirements, but so far, no improvement of survival was reported and side effects are frequent, particularly ischaemic events. Finally, we will discuss the current indications for vasopressin and its agonists in the setting of septic shock, and the remaining unresolved questions.

Family Care Rituals in the ICU to Reduce Symptoms of Post-Traumatic Stress Disorder in Family Members—A Multicenter, Multinational, Before-and-After Intervention Trial*



by Amass, Timothy H.; Villa, Gianluca; OMahony, Sean; Badger, James M.; McFadden, Rory; Walsh, Thomas; Caine, Tanis; McGuirl, Don; Palmisciano, Amy; Yeow, Mei-Ean; De Gaudio, Raffaele; Curtis, J. Randall; Levy, Mitchell M


Objectives: To assess the feasibility and efficacy of implementing “Family Care Rituals” as a means of engaging family members in the care of patients admitted to the ICU with a high risk of ICU mortality on outcomes including stress-related symptoms in family members.
Design: Prospective, before-and-after intervention evaluation.
Setting: Two U.S. academic medical ICU’s, and one Italian academic medical/surgical ICU.
Subjects: Family members of patients who had an attending predicted ICU mortality of greater than 30% within the first 24 hours of admission. Interventions: A novel intervention titled “Family Care Rituals” during which, following a baseline observation period, family members enrolled in the intervention phase were given an informational booklet outlining opportunities for engagement in care of the patient during their ICU stay.
Measurements and Main Results: Primary outcome was symptoms of post-traumatic stress disorder in family members 90 days after patient death or ICU discharge. Secondary outcomes included symptoms of depression, anxiety, and family satisfaction. At 90-day follow-up, 131 of 226 family members (58.0%) responded preintervention and 129 of 226 family members (57.1%) responded postintervention. Symptoms of post-traumatic stress disorder were significantly higher preintervention than postintervention (39.2% vs 27.1%; unadjusted odds ratio, 0.58; p = 0.046). There was no significant difference in symptoms of depression (26.5% vs 25.2%; unadjusted odds ratio, 0.93; p = 0.818), anxiety (41.0% vs 45.5%; unadjusted odds ratio, 1.20; p = 0.234), or mean satisfaction scores (85.1 vs 89.0; unadjusted odds ratio, 3.85; p = 0.052) preintervention versus postintervention 90 days after patient death or ICU discharge.
Conclusions: Offering opportunities such as family care rituals for family members to be involved with providing care for family members in the ICU was associated with reduced symptoms of post-traumatic stress disorder. This intervention may lessen the burden of stress-related symptoms in family members of ICU patients.

A lung rescue team improves survival in obesity with acute respiratory distress syndrome



by Gaetano Florio, Matteo Ferrari, Edward A. Bittner, Roberta De Santis Santiago, Massimiliano Pirrone, Jacopo Fumagalli, Maddalena Teggia Droghi, Cristina Mietto, Riccardo Pinciroli, Sheri Berg, Aranya Bagchi, Kenneth Shelton, Alexander Kuo, Yvonne Lai, Abraham Sonny, Peggy Lai…

Critical Care volume 24, Article number: 4 (2020) Published: 15 January 2020

Background
Limited data exist regarding ventilation in patients with class III obesity [body mass index (BMI) > 40 kg/m2] and acute respiratory distress syndrome (ARDS). The aim of the present study was to determine whether an individualized titration of mechanical ventilation according to cardiopulmonary physiology reduces the mortality in patients with class III obesity and ARDS.
Methods
In this retrospective study, we enrolled adults admitted to the ICU from 2012 to 2017 who had class III obesity and ARDS and received mechanical ventilation for > 48 h. Enrolled patients were divided in two cohorts: one cohort (2012–2014) had ventilator settings determined by the ARDSnet table for lower positive end-expiratory pressure/higher inspiratory fraction of oxygen (standard protocol-based cohort); the other cohort (2015–2017) had ventilator settings determined by an individualized protocol established by a lung rescue team (lung rescue team cohort). The lung rescue team used lung recruitment maneuvers, esophageal manometry, and hemodynamic monitoring.
Results
The standard protocol-based cohort included 70 patients (BMI = 49 ± 9 kg/m2), and the lung rescue team cohort included 50 patients (BMI = 54 ± 13 kg/m2). Patients in the standard protocol-based cohort compared to lung rescue team cohort had almost double the risk of dying at 28 days [31% versus 16%, P = 0.012; hazard ratio (HR) 0.32; 95% confidence interval (CI95%) 0.13–0.78] and 3 months (41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74), and this effect persisted at 6 months and 1 year (incidence of death unchanged 41% versus 22%, P = 0.006; HR 0.35; CI95% 0.16–0.74).
Conclusion
Individualized titration of mechanical ventilation by a lung rescue team was associated with decreased mortality compared to use of an ARDSnet table.

Should the ultrasound probe replace your stethoscope? A SICS-I sub-study comparing lung ultrasound and pulmonary auscultation in the critically ill



by Eline G. M. Cox, Geert Koster, Aidan Baron, Thomas Kaufmann, Ruben J. Eck, T. Corien Veenstra, Bart Hiemstra, Adrian Wong, Thomas C. Kwee, Jaap E. Tulleken, Frederik Keus, Renske Wiersema and Iwan C. C. van der Horst
Critical Care volume 24, Article number: 14 (2020) Published: 13 January 2020
Background
In critically ill patients, auscultation might be challenging as dorsal lung fields are difficult to reach in supine-positioned patients, and the environment is often noisy. In recent years, clinicians have started to consider lung ultrasound as a useful diagnostic tool for a variety of pulmonary pathologies, including pulmonary edema. The aim of this study was to compare lung ultrasound and pulmonary auscultation for detecting pulmonary edema in critically ill patients.
Methods
This study was a planned sub-study of the Simple Intensive Care Studies-I, a single-center, prospective observational study. All acutely admitted patients who were 18 years and older with an expected ICU stay of at least 24 h were eligible for inclusion. All patients underwent clinical examination combined with lung ultrasound, conducted by researchers not involved in patient care. Clinical examination included auscultation of the bilateral regions for crepitations and rhonchi. Lung ultrasound was conducted according to the Bedside Lung Ultrasound in Emergency protocol. Pulmonary edema was defined as three or more B lines in at least two (bilateral) scan sites. An agreement was described by using the Cohen κ coefficient, sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy. Subgroup analysis were performed in patients who were not mechanically ventilated.
Results
The Simple Intensive Care Studies-I cohort included 1075 patients, of whom 926 (86%) were eligible for inclusion in this analysis. Three hundred seven of the 926 patients (33%) fulfilled the criteria for pulmonary edema on lung ultrasound. In 156 (51%) of these patients, auscultation was normal. A total of 302 patients (32%) had audible crepitations or rhonchi upon auscultation. From 130 patients with crepitations, 86 patients (66%) had pulmonary edema on lung ultrasound, and from 209 patients with rhonchi, 96 patients (46%) had pulmonary edema on lung ultrasound. The agreement between auscultation findings and lung ultrasound diagnosis was poor (κ statistic 0.25). Subgroup analysis showed that the diagnostic accuracy of auscultation was better in non-ventilated than in ventilated patients.
Conclusion
The agreement between lung ultrasound and auscultation is poor.
Trial registration
NCT02912624. Registered on September 23, 2016.


Respiratory muscle ultrasonography: methodology, basic and advanced principles and clinical applications in ICU and ED patients—a narrative review





Respiratory muscle ultrasound is used to evaluate the anatomy and function of the respiratory muscle pump. It is a safe, repeatable, accurate, and non-invasive bedside technique that can be successfully applied in different settings, including general intensive care and the emergency department. Mastery of this technique allows the intensivist to rapidly diagnose and assess respiratory muscle dysfunction in critically ill patients and in patients with unexplained dyspnea. Furthermore, it can be used to assess patient–ventilator interaction and weaning failure in critically ill patients. This paper provides an overview of the basic and advanced principles underlying respiratory muscle ultrasound with an emphasis on the diaphragm. We review different ultrasound techniques useful for monitoring of the respiratory muscle pump and possible therapeutic consequences. Ideally, respiratory muscle ultrasound is used in conjunction with other components of critical care ultrasound to obtain a comprehensive evaluation of the critically ill patient. We propose the ABCDE-ultrasound approach, a systematic ultrasound evaluation of the heart, lungs and respiratory muscle pump, in patients with weaning failure.

Accuracy of ventilator-associated events for the diagnosis of ventilator-associated lower respiratory tract infections



by Olivier Pouly, Sylvain Lecailtel, Sophie Six, Sébastien Préau, Frédéric Wallet, Saad Nseir and Anahita Rouzé

Annals of Intensive Care volume 10, Article number: 6 (2020) Published: 13 January 2020


Background
The aim of this study was to investigate the concordance between ventilator-associated events (VAE) and ventilator-associated lower respiratory tract infections (VA-LRTI), and their impact on outcome.
Methods
This retrospective study was performed in five 10-bed ICUs of a teaching hospital, during a 2-year period. Ventilator-associated lower respiratory tract infections (VA-LRTI), including ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) were prospectively diagnosed. The agreement between VAE, VAT and VAP was assessed by k statistics.
Results
A total of 1059 patients (15,029 ventilator-days) were included. 268 VAP (17.8 per 1000 ventilator-days), 127 VAT (8.5 per 1000 ventilator-days) and 262 VAE (17.4 per 1000 ventilator-days) were diagnosed. There was no agreement between VAT and VAE, and the agreement was poor between VAP and VAE (k = 0.12, 95% CI 0.03–0.20). VAE and VA-LRTI were associated with significantly longer duration of mechanical ventilation, ICU and hospital length of stay. VAP, VAT and VAE were not significantly associated with mortality in multivariate analysis.
Conclusions
The agreement was poor between VAE and VAP. No agreement was found between VAE and VAT. VAE episodes were significantly associated with longer duration of mechanical ventilation and length of stay, but not with ICU mortality.

Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria



by Amol T. Kothekar, Jigeeshu Vasishtha Divatia, Sheila Nainan Myatra, Anand Patil, Manjunath Nookala Krishnamurthy, Harish Mallapura Maheshwarappa, Suhail Sarwar Siddiqui, Murari Gurjar, Sanjay Biswas and Vikram Gota

Annals of Intensive Care volume 10, Article number: 4 (2020) 

Background
Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40). We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock. We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100.
Methods
Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses. Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data. European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used.
Results
A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively. Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target. A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40. Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H).
Conclusions
In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires a bolus of 500 mg followed by EI of 1500 mg Q8H. While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.

C-reactive protein clustering to clarify persistent inflammation, immunosuppression and catabolism syndrome





Purpose
Among patients surviving treatment in intensive care units (ICU), some cases exist for which inflammation persisted with prolonged hospital stays, referred as persistent inflammatory, immunosuppressed, catabolic syndrome (PIICS). C reactive protein (CRP) is regarded as the most important marker for PIICS. Nevertheless, the applicable cut-off of CRP for PIICS has never been described in the literature.
Methods
Data of patients admitted to the ICU/Emergency ward from May 2015 through June 2019 were analyzed retrospectively. Using K-means clustering, a 14-day CRP transition dataset was analyzed and categorized finally into 7 classes: 4 PIICS classes and 3 non-PIICS classes. Outcomes and the other PIICS characteristics were evaluated.
Results
From all 5513 admitted patients, this study examined data of 539 patients who had been admitted for more than 14 days, and for whom 14 day CRP transition analysis could be performed. By the CRP transitions of 7 categorized classes, the CRP cut-off for PIICS was regarded as 3.0 mg/dl on day 14. The Barthel Index at discharge, albumin, and total lymphocyte counts on day 14 were significantly lower in PIICS classes than those of non-PIICS classes. Creatinine kinase, antithrombin activity and thrombomodulin on admission were regarded as independent risk factors for PIICS.
Conclusions
Among patients with prolonged hospital stay, the PIICS population had elevated CRP, but lower Barthel Index, albumin, and total lymphocyte counts. The criterion of day 14 CRP for PIICS should be 3.0 mg/dl.

Development of an Undergraduate Medical Education Critical Care Content Outline Utilizing the Delphi Method



by Smith, Andrew G.; Brainard, Jason C.; Campbell,


Objectives: No consensus exists on a standardized critical care content outline for medical student education. The aim of this research is to develop a national undergraduate medical education critical care content outline.
Design: The authors used a Delphi process to reach expert consensus on a content outline that identified the core critical care knowledge topics and procedural skills that medical students should learn prior to entering residency. Over three iterative rounds, the expert panel reached consensus on a critical care content outline.
Setting: An electronic survey of critical care medical educators, residency program directors, and residents in the United States.
Subjects: The expert panel included three groups as follows: 1) undergraduate medical education critical care educators, 2) residency program directors representing all core specialties, and 3) residents representing their core specialties. Interventions: None.
 Measurements and Main Results: The expert panel included 28 members. Experts represented the following medical specialties: anesthesiology, emergency medicine, internal medicine, obstetrics and gynecology, pediatrics, and surgery. Seventeen experts had subspecialty training in critical care. The expert panel identified 19 highly recommended critical care knowledge topics and procedural skills. These topics and procedural skills were grouped into five broad categories as follows: 1) neurologic, 2) respiratory, 3) cardiovascular, 4) renal and electrolytes, and 5) supplemental ICU topics. Bag-mask ventilation was the only procedural skill identified as highly recommended.
Conclusions: This study provides a national consensus undergraduate medical education critical care content outline. By including experts from multiple specialties, this content outline is meaningful for medical student education, independent of medical specialty. The content outline represents a first step in the development of a national undergraduate medical education critical care curriculum.

High Quality Targeted Temperature Management (TTM) After Cardiac Arrest



by Fabio Silvio Taccone, Edoardo Picetti and Jean-Louis Vincent 

Critical Care volume 24, Article number: 6 (2020)

Targeted temperature management (TTM) is a complex intervention used with the aim of minimizing post-anoxic injury and improving neurological outcome after cardiac arrest. There is large variability in the devices used to achieve cooling and in protocols (e.g., for induction, target temperature, maintenance, rewarming, sedation, management of post-TTM fever). This variability can explain the limited benefits of TTM that have sometimes been reported. We therefore propose the concept of “high-quality TTM” as a way to increase the effectiveness of TTM and standardize its use in future interventional studies.