Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock

Importance Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock—a condition due to excessive vasodilation, most frequently from severe infection. Blood pressure support with a noncatecholamine vasopressor may reduce stimulation of adrenergic receptors and decrease myocardial oxygen demand. Atrial fibrillation is common with catecholamines and is associated with adverse events, including mortality and increased length of stay (LOS). Objectives To determine whether treatment with vasopressin + catecholamine vasopressors compared with catecholamine vasopressors alone was associated with reductions in the risk of adverse events. Data Sources MEDLINE, EMBASE, and CENTRAL were searched from inception to February 2018. Experts were asked and meta-registries searched to identify ongoing trials. Study Selection Pairs of reviewers identified randomized clinical trials comparing vasopressin in combination with catecholamine vasopressors to catecholamines alone for patients with distributive shock. Data Extraction and Synthesis Two reviewers abstracted data independently. A random-effects model was used to combine data. Main Outcomes and Measures The primary outcome was atrial fibrillation. Other outcomes included mortality, requirement for renal replacement therapy (RRT), myocardial injury, ventricular arrhythmia, stroke, and LOS in the intensive care unit and hospital. Measures of association are reported as risk ratios (RRs) for clinical outcomes and mean differences for LOS. Results Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], −0.06 [95% CI, −0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, −0.04 [95% CI, −0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, −0.07 [95% CI, −0.12 to −0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes. Conclusions and Relevance In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied

Perspective of the Surviving Sepsis Campaign on the Management of Pediatric Sepsis in the Era of Coronavirus Disease 2019

Severe acute respiratory syndrome coronavirus 2 is a novel cause of organ dysfunction in children, presenting as either coronavirus disease 2019 with sepsis and/or respiratory failure or a hyperinflammatory shock syndrome. Clinicians must now consider these diagnoses when evaluating children for septic shock and sepsis-associated organ dysfunction. The Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-associated Organ Dysfunction in Children provide an appropriate framework for the early recognition and initial resuscitation of children with sepsis or septic shock caused by all pathogens, including severe acute respiratory syndrome coronavirus 2. However, the potential benefits of select adjunctive therapies may differ from non-coronavirus disease 2019 sepsis

Diagnosis of ventilator-associated pneumonia in critically ill adult patients-a systematic review and meta-analysis.

The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

OBJECTIVE: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." DESIGN: A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. RESULTS: The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. CONCLUSIONS: Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality

Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines.

To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness. We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We defined "early" EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds. We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion. We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access

The efficacy and safety of prokinetic agents in critically ill patients receiving enteral nutrition: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Intolerance to enteral nutrition is common in critically ill adults, and may result in significant morbidity including ileus, abdominal distension, vomiting and potential aspiration events. Prokinetic agents are prescribed to improve gastric emptying. However, the efficacy and safety of these agents in critically ill patients is not well-defined. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy and safety of prokinetic agents in critically ill patients. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library from inception up to January 2016. Eligible studies included randomized controlled trials (RCTs) of critically ill adults assigned to receive a prokinetic agent or placebo, and that reported relevant clinical outcomes. Two independent reviewers screened potentially eligible articles, selected eligible studies, and abstracted pertinent data. We calculated pooled relative risk (RR) for dichotomous outcomes and mean difference for continuous outcomes, with the corresponding 95 % confidence interval (CI). We assessed risk of bias using Cochrane risk of bias tool, and the quality of evidence using grading of recommendations assessment, development, and evaluation (GRADE) methodology. RESULTS: Thirteen RCTs (enrolling 1341 patients) met our inclusion criteria. Prokinetic agents significantly reduced feeding intolerance (RR 0.73, 95 % CI 0.55, 0.97; P = 0.03; moderate certainty), which translated to 17.3 % (95 % CI 5, 26.8 %) absolute reduction in feeding intolerance. Prokinetics also reduced the risk of developing high gastric residual volumes (RR 0.69; 95 % CI 0.52, 0.91; P = 0.009; moderate quality) and increased the success of post-pyloric feeding tube placement (RR 1.60, 95 % CI 1.17, 2.21; P = 0.004; moderate quality). There was no significant improvement in the risk of vomiting, diarrhea, intensive care unit (ICU) length of stay or mortality. Prokinetic agents also did not significantly increase the rate of diarrhea. CONCLUSION: There is moderate-quality evidence that prokinetic agents reduce feeding intolerance in critically ill patients compared to placebo or no intervention. However, the impact on other clinical outcomes such as pneumonia, mortality, and ICU length of stay is unclear

Expert consensus statements for the management of COVID-19-related acute respiratory failure using a Delphi method.

Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ <sup>2</sup> ) test (p < 0·05 was considered as unstable). Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. The study was registered with Clinical trials.gov Identifier: NCT04534569