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BackgroundThe rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU).MethodsThe SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations.ResultsThe SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. ConclusionThe SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Introduction Antimicrobial treatments for carbapenem-resistant Enterobacteriaceae (CRE) bacteremia are limited, with colistin-based regimens being a primary therapy. Ceftazidime-avibactam is an emerging treatment for various CRE infections. This study aimed to assess ceftazidime-avibactam effectiveness compared to colistin in patients with CRE bacteremia. Methods This retrospective, multi-centre study included adult patients with CRE bacteremia treated with ceftazidime-avibactam or colistin, from 01 September 2017 until 01 December 2020, at two tertiary centres in Saudi Arabia. The risk of 14-day mortality was compared between recipients of ceftazidime-avibactam versus colistin, using Cox multivariable regression, adjusted for Pitt score, Charlson Comorbidity Index score, and treatment with chemotherapy and immunosuppressive agents. Results We enrolled 61 patients; 32 received ceftazidime-avibactam, and 29 received colistin. The adjusted risk of 14-day mortality was lower in the ceftazidime-avibactam group than the colistin group (hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.10 – 0.99;P = 0.049), while the crude 14-day mortality was not different between the two antibiotics (HR, 0.59; 95% CI 0.21-1.66; P = 0.32). The clinical success rate was higher with the use of ceftazidime-avibactam versus colistin (46.8% versus 20.4%, respectively; P = 0.047). Conclusion Ceftazidime-avibactam was associated with a lower risk of 14-day mortality than colistin in patients with CRE bacteremia.

IMPORTANCE: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. OBJECTIVE: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. INTERVENTION: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). MAIN OUTCOMES AND MEASURES: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. RESULTS: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, −6.37% [95% CI, −15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, −1.15% [95% CI, −9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. CONCLUSIONS AND RELEVANCE: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04350723

Septic shock and acute respiratory distress syndrome (ARDS) are characterized by a dysregulated immune host response that may respond to steroid therapy. Eosinophils contribute to type 2 inflammation that often responds to steroid therapy; their role in immune dysregulation and outcomes in sepsis and ARDS is unclear.A systematic search of Cochrane Library, MEDLINE, and EMBASE was performed from inception to 9 September 2020. The search comprised the following terms: eosinophils, sepsis, septic shock, and ARDS. Two reviewers independently screened abstracts and texts and extracted data on disease severity and clinical outcomes.Thirty-nine studies were identified: 30 evaluated serum eosinophil count in sepsis, one evaluated eosinophil activity in sepsis, three assessed bronchoalveolar lavage (BAL) eosinophil count in ARDS, four assessed eosinophil activity in ARDS, and one assessed peripheral eosinophil count in ARDS. Eleven studies showed an association between eosinopenia and sepsis, and eight studies found persistent eosinopenia at48 hr of intensive care unit admission to predict mortality and readmission in septic patients. Three studies found BAL eosinophil count to be low in ARDS, although one found that levels rose in late-phase ARDS. Three studies found eosinophil activity markers in BAL to be high in ARDS and correlate with ARDS severity.Persistent peripheral eosinopenia is a marker of bacterial sepsis and is independently associated with poor outcomes. Bronchoalveolar lavage eosinophil counts are low in early-phase ARDS, but increase in late-phase ARDS, while elevated markers of eosinophil activity correlate with ARDS severity. Further studies understanding the mechanisms leading to eosinopenia in sepsis and increased eosinophil activity in ARDS are needed.RéSUMé: OBJECTIF: Le choc septique et le syndrome de détresse respiratoire aiguë (SDRA, ARDS en anglais) se caractérisent par une réponse immunitaire dérégulée chez l’hôte qui pourrait répondre à une corticothérapie. Les éosinophiles contribuent à l’inflammation de type 2, laquelle répond souvent à la corticothérapie; leur rôle dans la dérégulation immunitaire et les devenirs en cas de sepsis et de SDRA n’est pas clair.Une recherche systématique dans les bases de données Cochrane Library, MEDLINE et EMBASE a été réalisée de leur création au 9 septembre 2020. La recherche comprenait les termes suivants : éosinophiles, sepsis, choc septique et SDRA. Deux réviseurs ont examiné de manière indépendante les résumés et textes et ont extrait les données décrivant la gravité de la maladie et les devenirs cliniques.Trente-neuf études ont été identifiées : 30 études portaient sur le décompte d’éosinophiles sériques lors de sepsis, une étude examinait l’activité des éosinophiles dans un contexte de sepsis, trois ont évalué le décompte d’éosinophiles par lavage bronchoalvéolaire (LBA) dans les cas de SDRA, quatre ont examiné l’activité des éosinophiles dans le SDRA, et une a évalué le décompte d’éosinophiles périphériques dans les cas de SDRA. Onze études ont montré une association entre l’éosinopénie et le sepsis, et huit études ont remarqué qu’une éosinopédie persistante pour plus de 48 heures après l’admission à l’unité de soins intensifs était un prédicteur de mortalité et de réadmission chez les patients septiques. Trois études ont révélé que le nombre d’éosinophiles dans un LBA était faible en cas de SDRA, bien qu’une étude ait constaté que les taux augmentaient dans les SDRA de phase tardive. Trois études ont révélé que les marqueurs d’activité éosinophilique dans les LBA étaient élevés dans les cas de SDRA et étaient corrélés à la gravité du SDRA.L’éosinopénie périphérique persistante est un marqueur de sepsis bactérien et est indépendamment associée à de mauvais pronostics. Les décomptes d’éosinophiles dans les lavages bronchoalvéolaires sont bas dans les cas de SDRA en phase précoce, mais augmentent dans le SDRA en phase tardive, alors que des marqueurs élevés d’activité éosinophilique sont corrélés à la sévérité du SDRA. D’autres études visant à comprendre les mécanismes menant à l’éosinopénie dans le sepsis et à l’augmentation de l’activité éosinophilique dans le SDRA sont nécessaires.

Background:Speculations whether treatment with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARB) predisposes to severe coronavirus disease 2019 (COVID-19) or worsens its outcomes. This study assessed the association of ACE-I/ARB therapy with the development of severe COVID-19.Methods:This multi-center, prospective study enrolled patients hospitalized for COVID-19 and receiving one or more antihypertensive agents to manage either hypertension or cardiovascular disease. ACE-I/ARB therapy associations with severe COVID-19 on the day of hospitalization, intensive care unit (ICU) admission, mechanical ventilation and in-hospital death on follow-up were tested using a multivariate logistic regression model adjusted for age, obesity, and chronic illnesses. The composite outcome of mechanical ventilation and death was examined using the adjusted Cox multivariate regression model.Results:Of 338 enrolled patients, 245 (72.4%) were using ACE-I/ARB on the day of hospital admission, and 197 continued ACE-I/ARB therapy during hospitalization. Ninety-eight (29%) patients had a severe COVID-19, which was not significantly associated with the use of ACE-I/ARB (OR 1.17, 95% CI 0.66-2.09; P = .57). Prehospitalization ACE-I/ARB therapy was not associated with ICU admission, mechanical ventilation, or in-hospital death. Continuing ACE-I/ARB therapy during hospitalization was associated with decreased mortality (OR 0.22, 95% CI 0.073-0.67; P = .008). ACE-I/ARB use was not associated with developing the composite outcome of mechanical ventilation and in-hospital death (HR 0.95, 95% CI 0.51-1.78; P = .87) versus not using ACE-I/ARB.Conclusion:Patients with hypertension or cardiovascular diseases receiving ACE-I/ARB therapy are not at increased risk for severe COVID-19 on admission to the hospital. ICU admission, mechanical ventilation, and mortality are not associated with ACE-I/ARB therapy. Maintaining ACE-I/ARB therapy during hospitalization for COVID-19 lowers the likelihood of death.Clinical Trial Registration:ClinicalTrials.gov, NCT4357535.

Purpose: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU).Methods: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities.Results: The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia".Conclusion: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.Keywords: Clinical practice guideline; Dexmedetomidine; ICM-RPG; Sedation.© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.

Objective To determine the efficacy and safety of awake prone positioning versus usual care in non-intubated adults with hypoxemic respiratory failure due to covid-19. Design Systematic review with frequentist and bayesian meta-analyses. Study eligibility Randomized trials comparing awake prone positioning versus usual care in adults with covid-19 related hypoxemic respiratory failure. Information sources were Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to 4 March 2022. Data extraction and synthesis Two reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were performed for the primary and secondary outcomes. Bayesian meta-analyses were performed for endotracheal intubation and mortality outcomes. GRADE certainty of evidence was assessed for outcomes. Main outcome measures The primary outcome was endotracheal intubation. Secondary outcomes were mortality, ventilator-free days, intensive care unit (ICU) and hospital length of stay, escalation of oxygen modality, change in oxygenation and respiratory rate, and adverse events. Results 17 trials (2931 patients) met the eligibility criteria. 12 trials were at low risk of bias, three had some concerns, and two were at high risk. Awake prone positioning reduced the risk of endotracheal intubation compared with usual care (crude average 24.2% v 29.8%, relative risk 0.83, 95% confidence interval 0.73 to 0.94; high certainty). This translates to 55 fewer intubations per 1000 patients (95% confidence interval 87 to 19 fewer intubations). Awake prone positioning did not significantly affect secondary outcomes, including mortality (15.6% v 17.2%, relative risk 0.90, 0.76 to 1.07; high certainty), ventilator-free days (mean difference 0.97 days, 95% confidence interval −0.5 to 3.4; low certainty), ICU length of stay (−2.1 days, −4.5 to 0.4; low certainty), hospital length of stay (−0.09 days, −0.69 to 0.51; moderate certainty), and escalation of oxygen modality (21.4% v 23.0%, relative risk 1.04, 0.74 to 1.44; low certainty). Adverse events related to awake prone positioning were uncommon. Bayesian meta-analysis showed a high probability of benefit with awake prone positioning for endotracheal intubation (non-informative prior, mean relative risk 0.83, 95% credible interval 0.70 to 0.97; posterior probability for relative risk Conclusions Awake prone positioning compared with usual care reduces the risk of endotracheal intubation in adults with hypoxemic respiratory failure due to covid-19 but probably has little to no effect on mortality or other outcomes. Systematic review registration PROSPERO CRD42022314856.

BackgroundCoronavirus disease 2019 (COVID-19), may progress to respiratory failure requiring invasive mechanical ventilation. Due to ventilator shortage and healthcare systems strain, affordable interventions such as awake prone positioning has been used to improve oxygenation, however, the effect of this intervention on patient-important outcomes is uncertain. The COVI-PRONE trial aims to determine if awake prone positioning in hypoxemic COVID-19 patients reduces the need for invasive mechanical ventilation.Study designA pragmatic, multicenter, international, parallel-group, and stratified randomized controlled trial, aiming to enrol 400 hospitalized adults with COVID-19.ParticipantsThe target population is hospitalized adults with confirmed or suspected COVID-19, hypoxemia that requires ≥40% oxygen or ≥ 5 L/min by nasal cannula, and abnormal chest x-ray. We will exclude patients with any of the following: immediate need for intubation; altered mental status; contraindication to prone positioning; hemodynamic instability; body mass index > 40 kg/m2; third trimester pregnancy; do not intubate status; previous enrolment or intubation within the same hospital admission; and prone positioning for more than one day prior to randomization.Study intervention and controlFollowing informed a priori or deferred consent, eligible patients will be centrally randomized to either the intervention arm (prone positioning) or standard of care (no prone positioning). Patients randomized to the prone position will be required to either self-prone or assist-prone for a total of eight to ten hours per day until they meet pre-specified stopping criteria.Study outcomesThe primary outcome is invasive mechanical ventilation at 30-days of randomization. Other outcomes include mortality at 60 days, invasive and non-invasive mechanical ventilation free days at 30 days, hospital length of stay at 60 days, days alive and outside of the hospital at 60 days, complications of proning, and serious adverse events.

IntroductionNoninvasive ventilation delivered by helmet is has been used for respiratory support of patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. The aim of this study is to compare helmet noninvasive ventilation with usual care versus usual care alone to reduce the mortality.Methods and analysisThis is a multicenter, pragmatic, parallel, randomized controlled trial that compares helmet noninvasive ventilation with usual care to usual care alone in 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness.Ethics and disseminationApprovals are obtained from the Institutional Review Boards (IRBs) of each participating institution. Our findings will be published in peer-review journals and presented at relevant conferences and meetings.Trial registration numberNCT04477668 registered on July 20, 2020Article SummaryStrengths and limitations of this studyThis trial compares helmet NIV to usual care for respiratory support of patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.The trial is a multi-center, pragmatic, parallel randomized controlled trial.The main limitation is the unblinded design due to the nature of the intervention.

IntroductionNon-invasive ventilation (NIV) delivered by helmet has been used for respiratory support of patients with acute hypoxaemic respiratory failure due to COVID-19 pneumonia. The aim of this study was to compare helmet NIV with usual care versus usual care alone to reduce mortality.Methods and analysisThis is a multicentre, pragmatic, parallel randomised controlled trial that compares helmet NIV with usual care to usual care alone in a 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness.Ethics and disseminationApprovals are obtained from the institutional review boards of each participating institution. Our findings will be published in peer-reviewed journals and presented at relevant conferences and meetings.Trial registration numberNCT04477668.

ImportanceHelmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited.ObjectiveTo evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.Design, Setting, and ParticipantsThis was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021.InterventionsPatients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen.Main Outcomes and MeasuresThe primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events.ResultsAmong 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, −8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, −3.1% [95% CI, −14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group.Conclusions and RelevanceResults of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm.Trial RegistrationClinicalTrials.gov Identifier: NCT04477668

Background and objectiveNoninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation having multiple advantages over other support modalities but data about effectiveness are limited.MethodsIn this multicenter randomized trial of helmet non-invasive ventilation for COVID-19 patients (Helmet-COVID), 320 adult ICU patients with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (with a ratio of arterial oxygen partial pressure to fraction (percent) of inspired oxygen (PaO2/FiO2) 10 L/min or above) will be randomized to helmet-noninvasive ventilation with usual care or usual care alone. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction from 40% to 25%.ConclusionConsistent with international guidelines, we developed a detailed plan to guide the analysis of the Helmet-COVID trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes to facilitate unbiased analyses of clinical data.Trial registrationClinicaltrials.gov: NCT04477668 (registered on July 20, 2020)

BACKGROUND: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. METHODS: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. RESULTS: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. CONCLUSION: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.

OBJECTIVES In this systematic review and meta-analysis, we assessed whether a high CO2 gap predicts mortality in adult critically ill patients with circulatory shock. DATA SOURCES A systematic search of MEDLINE and EMBASE electronic databases from inception to October 2019. STUDY SELECTION Studies from adult (age ≥ 18 yr) ICU patients with shock reporting CO2 gap and outcomes of interest. Case reports and conference abstracts were excluded. DATA EXTRACTION Data extraction and study quality assessment were performed independently in duplicate. DATA SYNTHESIS We used the Newcastle-Ottawa Scale to assess methodological study quality. Effect sizes were pooled using a random-effects model. The primary outcome was mortality (28 d and hospital). Secondary outcomes were ICU length of stay, hospital length of stay, duration of mechanical ventilation, use of renal replacement therapy, use of vasopressors and inotropes, and association with cardiac index, lactate, and central venous oxygen saturation. CONCLUSIONS We included 21 studies (n = 2,155 patients) from medical (n = 925), cardiovascular (n = 685), surgical (n = 483), and mixed (n = 62) ICUs. A high CO2 gap was associated with increased mortality (odds ratio, 2.22; 95% CI, 1.30-3.82; p = 0.004) in patients with shock, but only those from medical and surgical ICUs. A high CO2 gap was associated with higher lactate levels (mean difference 0.44 mmol/L; 95% CI, 0.20-0.68 mmol/L; p = 0.0004), lower cardiac index (mean difference, -0.76 L/min/m; 95% CI, -1.04 to -0.49 L/min/m; p = 0.00001), and central venous oxygen saturation (mean difference, -5.07; 95% CI, -7.78 to -2.37; p = 0.0002). A high CO2 gap was not associated with longer ICU or hospital length of stays, requirement for renal replacement therapy, longer duration of mechanical ventilation, or higher vasopressors and inotropes use. Future studies should evaluate whether resuscitation aimed at closing the CO2 gap improves mortality in shock.

Enoxaparin is indicated for thromboprophylaxis in non-orthopedic surgical patients at a fixed dose of 40 mg daily. According to the US Food and Drug Administration’s enoxaparin prescribing information, this dose exposes low-weight patients (males < 57 kg, females < 45 kg) to a higher risk of bleeding. This study aimed to determine the rate of achieving a prophylactic peak anti-factor Xa (AFXa) level in low-weight surgical patients using enoxaparin 30 mg daily. Low-weight patients admitted for abdominopelvic or noncardiac thoracic surgery from May 2018 to May 2019 were prospectively studied. After receiving daily enoxaparin 30 mg, peak AFXa levels were assessed for achieving a prophylactic level (0.2-0.5 IU/mL). In 121 patients, the proportion of achieving a prophylactic peak AFXa level was 66.1%. More females (84.8%) achieved a prophylactic level compared to males (54.7%, P = .001). All out-of-range peak AFXa levels (33.9%) were sub-prophylactic. The median peak AFXa level was lower in males (0.24 [0.1-0.47] IU/mL) than females (0.31 [0.1-0.5] IU/mL; P < .001). On univariate analysis, female sex and weight were associated with achieving a prophylactic peak AFXa level. On multivariate analysis, only female sex was independently associated with an adequate prophylactic AFXa level (odds ratio 3.17, 95% CI: 1.32-11.94; P = .014). Four venous thromboembolism events (3.3%) were observed in patients with sub-prophylactic peak AFXa levels (9.7%). Two-thirds of low-weight surgical patients achieved a prophylactic peak AFXa level using daily enoxaparin 30 mg. This dose is likely to provide adequate thromboprophylaxis in low-weight females.

Purpose Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS. Methods We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries (ClinicalTrials.gov, ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data. Results Seven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86–1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57–0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35–0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain. Conclusions Inconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review.

The aim of this prospective, randomized study was to compare the effects of tigecycline and imipenem-cilastatin on fibrinogen levels in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients were empirically randomized to receive tigecycline or imipenem-cilastatin. Fibrinogen levels were measured in both patient groups on days 1, 3, 5 and 8 of antibiotic therapy and 3 days after antibiotic therapy completion. Twenty patients received tigecycline and 22 patients received imipenem-cilastatin . Patients in the tigecycline group had lower mean fibrinogen levels compared to those in the imipenem-cilastatin group on day 3 (4.1 ± 1.2 vs. 5.9 ± 1.3 g/L; p 0.001), day 5 (3.7 ± 1.2 vs. 6.5 ± 1.1 g/L; p 0.001), day 8 (3.5 ± 1.3 vs. 5.8 ± 1.6 g/L; p 0.001), and day 3 after antibiotic completion (4.1 ± 1.4 vs. 6.1 ± 1.6 g/L; p 0.001). In conclusion, compared to imipenem-cilastatin, tigecycline was associated with a significant decrease in fibrinogen levels, following CRS and HIPEC.

Purpose of review Upper gastrointestinal bleeding (UGIB) is a common condition that can lead to significant morbidity and mortality. Critical care physicians usually get involved in the care of patients with severe UGIB that is associated with hemodynamic compromise. We aim to provide the readers with evidence-based review of the management of patients with severe UGIB. Recent findings Proton pump inhibitors are the main pharmacologic intervention for UGIB, along with adequate resuscitation and timely endoscopic intervention. Endoscopic therapy should be performed as soon as haemodynamics stabilization is achieved, which requires team collaboration. Several radiologic interventions are now commonly used as a second-line intervention after endoscopy. Summary The management of severe UGIB requires multidisciplinary collaboration, prompt recognition and resuscitation, carful use of blood products, early correction of coagulopathy, and early endoscopic or radiologic interventions.

Background: Although recent international guidelines have been published on the management of critically ill patients with the novel coronavirus disease 2019 (COVID-19), there is a vital need to develop clinical practice guidelines tailored to the context of Saudi Arabia. Methods: The Saudi Critical Care Society (SCCS) is the sponsor for this guideline. The expert panel consisted of 19 members. All members completed the World Health Organization Conflict of Interest Form. The expert panel formulated questions on the management of critically ill patients in the intensive care unit with COVID-19. Panel members identified relevant studies. The panel used the categories of Grading Recommendations, Assessment, Development, and Evaluation (GRADE) to assess the confidence in the evidence. Results: The SCCS expert panel issued 53 statements; of which 7 were strong recommendations, 9 were best practice statements, 32 were weak recommendations, and we were not able to issue recommendations in 5 instances. The statements covered different aspects of the critical illness in COVID-19 patients, including: infection control; therapeutic interventions; supportive care; and crisis management. Conclusion: The SCCS guidelines on the management of critically ill COVID-19 patients have been based on the best available evidence and tailored to the context of Saudi Arabia. These guidelines will be updated periodically to incorporate new evidence.