The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section.

BACKGROUND: The 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). METHODS: The 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. RESULTS: The 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. CONCLUSION: The 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.

The cuff leak test in critically ill patients: An international survey of intensivists.

BACKGROUND: The cuff leak test (CLT) is used to assess laryngeal edema prior to extubation. There is limited evidence for its diagnostic accuracy and conflicting guidelines surrounding its use in critically ill patients who do not have risk factors for laryngeal edema. The primary study aim was to describe intensivists' beliefs, attitudes, and practice regarding the use of the CLT. METHODS: A 13-item survey was developed, pilot-tested, and subjected to clinical sensibility testing. The survey was distributed electronically through MetaClinician®. Descriptive statistics and multivariable regression analysis were performed to examine associations between participant demographics and survey responses. RESULTS: 1184 practicing intensivists from 17 countries in North and South America, Europe, Oceania, and Asia participated. The majority (59%) of respondents reported rarely or never perform the CLT prior to extubating patients not at high risk of laryngeal edema, which correlated with 54% of respondents reporting they believed a failed CLT did not predict reintubation. Intensivists from the Middle East were 2.4 times more likely to request a CLT compared to those from North America. Intensivists with base training in medicine or emergency medicine were more likely to request a CLT prior to extubation compared to those with base training in anesthesiology. CONCLUSION: Use of the CLT prior to extubating patients not at high risk of laryngeal edema in the intensive care unit is highly variable. Practice appears to be influenced by country of practice and base specialty training.

Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials.

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.

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.

Extracorporeal liver support in patients with liver failure: a systematic review and meta-analysis of randomized trials.

PURPOSE: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) are associated with significant mortality and morbidity. Extracorporeal liver support (ECLS) devices have been used as a bridge to liver transplant; however, the efficacy and safety of ECLS are unclear. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the efficacy and safety of ECLS in liver failure. METHODS: We searched MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through March 13, 2019. RCTs comparing ECLS to usual care in ALF or ACLF were included. We used the Grading of Recommendations Assessment, Development and Evaluation approach to assess the certainty of the evidence. RESULTS: We identified 25 RCTs (1796 patients). ECLS use was associated with reduction in mortality (RR 0.84; 95% CI 0.74, 0.96, moderate certainty) and improvement in hepatic encephalopathy (HE) (RR 0.71; 95% CI 0.60, 0.84, low certainty) in patients with ALF or ACLF. The effect of ECLS on hypotension (RR 1.46; 95% CI 0.98, 2.2, low certainty), bleeding (RR 1.21; 95% CI 0.88, 1.66, moderate certainty), thrombocytopenia (RR 1.62; 95% CI 1.0, 2.64, very low certainty) and line infection (RR 1.92; 95% CI 0.11, 33.44, low certainty) was uncertain. CONCLUSIONS: ECLS may reduce mortality and improve HE in patients with ALF and ACLF. The effect on other outcomes is uncertain. However, the evidence is limited by risk of bias and imprecision, and larger trials are needed to better determine the effect of ECLS on patient-important outcomes.

Cuff Leak Test and Airway Obstruction in Mechanically Ventilated ICU Patients (COMIC): a pilot randomised controlled trial protocol.

INTRODUCTION: Endotracheal intubation and invasive mechanical ventilation are lifesaving interventions that are commonly performed in the intensive care unit (ICU). Laryngeal oedema is a known complication of intubation that may cause airway obstruction in a patient on extubation. To date, the only test available to predict this complication is the cuff leak test (CLT); however, its diagnostic accuracy and utility remains uncertain. Herein, we report the protocol for the CuffLeak and AirwayObstruction in MechanicallyVentilated ICU Patients (COMIC) pilottrial. METHODS AND ANALYSIS: This will be a multicentred, pragmatic, pilot randomised controlled trial (RCT). We will enrol 100 mechanically ventilated patients in the ICU who are deemed ready for extubation. We will exclude patients at a high risk of laryngeal oedema. All enrolled patients will have a CLT done before extubation. In the intervention arm, the results of the CLT will be communicated to the bedside physician, and decision to extubate will be left to the treating team. In the control arm, respiratory therapist will not communicate the results of the CLT to the treating physician, and the patient will be extubated regardless of the CLT result. Randomisation will be done in a 1:1 allocation ratio, stratified by size of the endotracheal tube and duration of invasive mechanical ventilation.Although we will examine all clinical outcomes relevant for the future COMIC RCT, the primary outcomes of the COMIC pilottrial will be feasibility outcomes including: consent rate, recruitment rate and protocol adherence. Clinical outcomes include postextubation stridor, reintubation, emergency surgical airway, ICU mortality, in hospital mortality, duration of mechanical ventilation and ICU length of stay in days. ETHICS AND DISSEMINATION: The Hamilton Integrated Research Ethics Board, Imam Abdulrahman Bin Faisal University Institutional Review Board and Bioethical Commission of the Jagiellonian University approved this study. The trial results will be disseminated via publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03372707.

Prophylactic Endotracheal Intubation in Patients with Upper Gastrointestinal Bleeding Undergoing Endoscopy: A Systematic Review and Meta-analysis.

BACKGROUND: Patients with upper gastrointestinal bleeding (UGIB) often require urgent or emergent esophagogastroduodenoscopy (EGD) and are at risk of complications such as aspiration of gastric content or blood. The role of prophylactic endotracheal intubation (PEI) in the absence of usual respiratory status-related indications is not well established. METHODS: We searched Medline, EMBASE, Cochrane Library's Central Register of Controlled Trials (CENTRAL) and SCOPUS from inception through July 2017 without date or language of publication restriction. We included studies that compared PEI with usual care (UC) in patients with acute UGIB, and reported any of the following outcomes: aspiration, pneumonia, mortality and length of stay. We excluded studies in which majority of included patients required intubation due to respiratory failure or decreased level of consciousness. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence for each outcome. RESULTS: We did not identify any randomized trials on this topic. We included 10 observational studies (n = 6068). We were not able to perform any adjusted analyses. PEI was associated with a significant increase in aspiration (OR 3.85, 95% CI, 1.46, 10.25; P = 0.01; I2 = 56%; low-quality evidence), pneumonia (OR 4.17, 95% CI, 1.82, 9.57; P = 0.0007; I2 =52%; low-quality evidence) and hospital length of stay (mean difference 0.86 days, 95% CI 0.13, 1.59; P = 0.02; I2 = 0; low-quality evidence), without clear effect on mortality (OR 1.92, 95% CI, 0.71, 5.23; P = 0.2; I2 = 95%; very low-quality evidence). CONCLUSIONS: Low- to very low-quality evidence from observational studies suggests that PEI in the setting of UGIB may be associated with higher rates of respiratory complications and, less likely, with increased mortality. Although the results are alarming, the lack of higher quality evidence calls for randomized trials to inform practice.

Making the McMOST out of Milestones and Objectives: Reimagining Standard Setting Using the McMaster Milestones and Objectives Stratification Technique.

BACKGROUND: As we enter the era of milestones and competency-based medical education (CBME), there is an increasing need to examine the procedures for stratifying objectives into levels of achievement. Most techniques used to date (e.g., Delphi surveys) involve some sort of consensus-based process, essentially crowd-sourcing wisdom of multiple educators to set anticipated milestones. In most graduate education settings, however, many simply use the judgment of one or two educators when setting educational objectives. Meanwhile, standard-setting procedures have been historically used in medical education for setting cut-points to determine levels of acceptable performance and do so in a more robust manner. OBJECTIVES: Inspired by these standard-setting procedures, the authors sought to develop a new way to stratify objectives into three relative levels of achievement (junior [ACGME level 1], intermediate [ACGME level 2-3], senior [ACGME level 4]). METHODS: The authors describe a novel, stepwise method that is composed of four steps. There are four steps to the McMOST procedure: 1) sorting objectives with a group of experienced teachers, 2) factor analysis to group preferences, 3) labeling components and reorganizing groupings, and 4) confirmation and final review by educational and content experts. RESULTS: Using McMOST method resulted in a change of placement for 15 of 34 (44%) of the milestones and improved agreement in two of three levels (intermediate from intraclass correlation of 0.56 to 0.80; senior from 0.69 to 0.79). CONCLUSIONS: The authors describe a novel protocol for stratifying objectives that may be useful to stratify and sort competencies into various levels of achievement (e.g., milestones) in this era of CBME.

Development and Validation of the McMaster Prescribing Competency Assessment for Medical Trainees (MacPCA).

BACKGROUND: Prescribing is an essential skill for all physicians, built on knowledge of clinical pharmacology, therapeutics and toxicology across the life cycle. The decline in organized clinical pharmacology training in medical schools, combined with an expanding pharmacopeia and increasing complexity of patient care, makes prescribing competency difficult for medical students to master. OBJECTIVES: To develop and validate the McMaster Prescribing Competency Assessment (MacPCA), an online tool suitable for evaluating clinical pharmacology knowledge and prescribing skills of medical trainees in Canada. METHODS: The MacPCA was developed using an online examination platform scalable to multiple sites across Canada. Questions represented 8 domains of safe and effective prescribing with level of difficulty aimed at a final year medical student. Validation assessment concentrated on face and construct validity. RESULTS: 58 participants (7, 12 and 21 medical students in Years 1, 2, and 3, respectively and 8 undergraduate controls) were recruited. Mean scores were 31% (SD 13.6), 46% (SD 14.9), 75% (SD 8.3) and 81% (SD 10.5) for the controls, Year 1, Year 2, and Year 3 (final year) students, respectively. Combined Year 2/Year 3 scores were significantly better than control/Year 1 scores (p<0.0001). Final year student feedback indicated the test was fair, clear and unambiguous, aimed at the right level, with sufficient time for completion. CONCLUSIONS: The MacPCA demonstrated good face validity and successfully discriminated between upper year medical students and their junior colleagues. Further expansion of testing and validation is warranted.

Clinical education guideline creation by residents for junior learners in emergency medicine: a novel educational experience.

Clinical practice guidelines are an important vehicle for knowledge translation and improving patient care. For most learners, these documents can be daunting and confusing. We describe a novel educational experience that clarified the guideline generation process for learners while at the same time creating clinical educational guidelines (simplified learning aids) for junior learners in the emergency department (ED). We devised a system using near-peer mentors to generate a series of clinical education guideline learning materials created by residents and junior learners for the evaluation of undifferentiated chest pain in the ED. This process assisted in teaching residents and junior learners and generated an endurable educational product.

Intra-aortic balloon pump in patients with cardiogenic shock complicating myocardial infarction: a systematic review and meta-analysis of randomized trials (protocol).

BACKGROUND: Cardiogenic shock is the leading cause of death in patients with acute myocardial infarction. Despite significant advancements in health technology and research, hospital mortality approaches 50%. The intra-aortic balloon pump is a mechanical hemodynamic assist device that has been used for over 40 years in the management of patients with cardiogenic shock. A recent randomized trial suggests that the use of intra-aortic balloon pumps does not reduce mortality in patients with ischemic cardiogenic shock. METHODS: We plan to search MEDLINE, EMBASE, and the Cochrane Trial Registry for potentially eligible randomized trials that compare the use of intra-aortic balloon pump with no mechanical device support in patients with cardiogenic shock. No date, language or journal limitations will be applied. Two reviewers will independently screen and identify eligible studies using predefined eligibility criteria. Data abstraction will be done independently and in duplicate. We plan to use RevMan software to generate pooled estimates across included studies, using the previously published method of DerSimonian and Laird. We will report pooled estimates as risk ratios with 95% confidence intervals for binary outcomes, and as mean differences with 95% confidence intervals for continuous outcomes. We will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. DISCUSSION: The aim of this systematic review and meta-analysis is to summarize the available evidence on the efficacy of the intra-aortic balloon pump in cardiogenic shock. Systematic review registration: PROSPERO CRD42014007056.

N-acetylcysteine as a novel prophylactic treatment for ifosfamide-induced nephrotoxicity in children: translational pharmacokinetics.

Ifosfamide (IFO), which is used in the treatment of pediatric solid tumors, causes high rates of nephrotoxicity. N-acetylcysteine (NAC), an antidote for acetaminophen overdose, has been shown to prevent IFO-induced renal cell death and nephrotoxicity in both LLCPK-1 cells and a rat model. To facilitate the use of NAC in preventing IFO-induced nephrotoxicity in children, the authors compared the systemic exposure to NAC in children treated for acetaminophen overdose to the systemic exposure of the therapeutically effective rat model. The mean systemic exposure in the rat model was 18.72 mM·h (range, 9.92-30.02 mM·h), compared to the mean systemic exposure found in treated children (14.48 mM·h; range, 6.22-32.96 mM·h). They also report 2 pediatric cases in which NAC-attenuated acute renal failure associated with IFO when given concurrently with their chemotherapy treatment. Systemic exposure to NAC measured in 1 of these cases was comparable to that in the children treated for acetaminophen overdose. These results corroborate NAC's potential to protect against IFO-induced nephrotoxicity in children when used in its clinically approved dose schedule and supports a clinical trial in children.

Nail embolization to the femoral artery.

Modern air-nailing tools are known to cause penetrating trauma. We report the unusual case of a pneumatically fired carpenter's nail that penetrated the chest of a 30-year-old man and subsequently embolized from the heart to the left femoral artery without clinical evidence of having entered the heart. The nail was surgically removed, and the patient was discharged from hospital without sequelae after 10 days. This case and the relevant literature are discussed from the perspective of the emergency department investigation and care of such patients.