Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis.

Background: The optimal resuscitative fluid remains controversial. Objective: To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2 = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2 = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2 = 42%). Conclusion and Relevance: Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.

Midodrine as an Adjuvant to Intravenous Vasopressor Agents in Adults With Resolving Shock: Systematic Review and Meta-Analysis.

PURPOSE: To evaluate the effects of midodrine in addition to intravenous vasopressor therapy on outcomes in adults recovering from shock. MATERIALS AND METHODS: PubMed, Scopus, Clinicaltrials.gov, and published abstracts were searched from inception to November 2018 for studies comparing outcomes in shock after midodrine initiation versus no midodrine. RESULTS: Three studies with 2533 patients were included. Patients in whom midodrine was added to intravenous vasopressor therapy compared to intravenous vasopressor therapy alone experienced similar intensive care unit (ICU; mean difference [MD]: 1.38 days, 95% confidence interval [CI]: -3.48 to 6.23, I2 = 93%) and hospital lengths of stay (MD: 4.37 days, 95% CI: -3.45 to 12.19, I2 = 93%) and intravenous vasopressor duration after midodrine initiation (MD: 7.28 days, 95% CI: -0.86 to 15.41, I2 = 97%). Mortality was similar between groups (odds ratio: 0.74, 95% CI: 0.44-1.27, I2 = 65%). Qualitative assessment of reporting biases revealed minimal location bias, moderate selective outcome reporting bias, no selective analysis reporting bias, and no conflict of interest bias. CONCLUSIONS: Midodrine had no effect on ICU or hospital length of stay. These results were highly susceptible to the study heterogeneity and availability. Future investigation into standardized initiation of midodrine at an adequate dosage with an expedited titration strategy is needed in order to assess the utility of this strategy in shock management.

Major publications in critical care pharmacotherapy literature in 2018.

PURPOSE: To summarize selected original critical care pharmacotherapy research published in 2018. MATERIALS AND METHODS: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 32 journals monthly for impactful articles and reviewed 100 articles during 2018. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria were applied to all relevant articles included in the monthly CCPLU. Articles with a 1A grade, including one clinical practice guideline, two meta-analyses, and ten original research trials, were selected for review. RESULTS: Clinical practice guidelines for the management of pain, agitation, delirium, immobility, and sleep disruption were summarized. Meta-analyses on the role of corticosteroids in sepsis and early enteral nutrition were reviewed. Included original research trials evaluated corticosteroids in sepsis, enteral and parenteral nutrition in patients with shock, tenecteplase in acute ischemic stroke, antipsychotics for the treatment of intensive care unit delirium, vasopressors in cardiogenic shock, balanced crystalloids and saline for fluid administration, and meropenem and piperacillin-tazobactam for treatment of resistant Gram-negative organisms. CONCLUSION: This clinical review and expert commentary of impactful critical care pharmacotherapy publications in 2018 provides perspectives and insights for the critical care practitioner.

Safety, efficacy, and cost of four-factor prothrombin complex concentrate (4F-PCC) in patients with factor Xa inhibitor-related bleeding: a retrospective study.

Oral factor Xa (fXa) inhibitor-related bleeding is a concerning drug safety problem. There is considerable controversy surrounding available reversal strategies. The recently approved reversal agent andexanet alfa has limited data, an unclear safety profile, and imparts a substantial financial burden. This has led to the off-label use of four-factor prothrombin complex concentrates (4F-PCC) for this indication. This study aimed to assess the safety and efficacy of 4F-PCC for the management of major bleeding related to oral fXa inhibitors. This observational, retrospective study included adult patients admitted from 2014 to 2018 who received 4F-PCC (Kcentra®) for fXa inhibitor-related major bleeding. Efficacy was assessed using criteria described by Sarode et al. Secondary outcomes included the incidence of thromboembolism, mortality, and a cost analysis comparing 4F-PCC to andexanet alfa for reversal of oral fXa inhibitors. Thirty-one patients received 4F-PCC for major bleeding associated with apixaban (55%) or rivaroxaban (45%). Intracranial hemorrhage (58%) and pericardial effusion (16%) accounted for the majority of bleeding events. Most patients received a single weight-based 4F-PCC dose of 25 units/kg (38.7%) or 50 units/kg (51.6%). Effective hemostasis was achieved in 80.6% of patients. Five patients (16%) died due to acute bleeding and no thromboembolic events were observed. Administration of 4F-PCC was effective for most patients requiring emergent reversal of anticoagulation with apixaban or rivaroxaban and was associated with a low risk of thromboembolic events. Considerable cost differences limit the use of andexanet alfa and may warrant further study of 4F-PCC for fXa inhibitor reversal.

Systematic Review of the Clinical Utility of Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Screening for MRSA Pneumonia.

OBJECTIVE: To describe the diagnostic performance characteristics of methicillin-resistant Staphylococcus aureus (MRSA) nasal screening for patients with pneumonia. DATA SOURCES: PubMed and Scopus were searched from 1 January 1990 to 12 December 2018 using terms methicillin-resistant Staphylococcus aureus AND (screening OR active surveillance OR surveillance culture OR targeted surveillance OR chromogenic OR PCR OR polymerase chain reaction OR rapid test) AND (nares OR nasal) AND (pneumonia OR respiratory). STUDY SELECTION AND DATA EXTRACTION: Relevant studies in humans and English were considered. DATA SYNTHESIS: In all, 19 studies, including 21 790 patients, were included. Nasal screening for MRSA had a high negative predictive value (NPV; 76% to 99.4% for relevant studies) across all types of pneumonia. Time from nasal screening to culture varied across studies. Relevance to Patient Care and Clinical Practice: MRSA nasal screening has a high NPV for MRSA involvement in pneumonia. Utilizing this test for antimicrobial stewardship program (ASP) purposes can provide a valuable tool for reducing unwarranted anti-MRSA agents and may provide additional cost benefits. A cutoff of 7 days between nasal swab and culture or infection onset seems most appropriate for use of this test for anti-MRSA agent de-escalation for ASP purposes. CONCLUSIONS: Consideration for the inclusion of the utility of MRSA nasal screening in MRSA pneumonia should be made for future pneumonia and ASP guidelines. Additional studies are warranted to fully evaluate specific pneumonia classifications, culture types, culture timing, and clinical outcomes associated with the use of this test in patients with pneumonia.

Acute Decompensated Heart Failure.

Heart failure (HF) is a societal burden due to its high prevalence, frequent admissions for acute decompensated heart failure (ADHF), and the economic impact of direct and indirect costs associated with HF and ADHF. Common etiologies of ADHF include medication and diet noncompliance, arrhythmias, deterioration in renal function, poorly controlled hypertension, myocardial infarction, and infections. Appropriate medical management of ADHF in patients is guided by the identification of signs and symptoms of fluid overload or low cardiac output and utilization of evidence-based practices. In patients with fluid overload, various strategies for diuresis or ultrafiltration may be considered. Depending on hemodynamics and patient characteristics, vasodilator, inotropic, or vasopressor therapies may be of benefit. Upon ADHF resolution, patients should be medically optimized, have lifestyle modifications discussed and implemented, and medication concierge service considered. After discharge, a multidisciplinary HF team should follow up with the patient to ensure a safe transition of care. This review article evaluates the management options and considerations when treating a patient with ADHF.

Oral Agents for the Management of Agitation and Agitated Delirium in Critically Ill Patients.

Agitation is one of the most common issues that critically ill patients experience. Medications used to manage agitation are often administered intravenously or intramuscularly in the acutely agitated, critically ill patient. However, a multimodal approach that utilizes multiple routes of administration may be appropriate. This review summarizes the available literature on oral antipsychotics, clonidine, and valproic acid to manage agitation in critically ill patients while also focusing on their pharmacology and appropriate monitoring. Despite inconclusive findings from different studies, antipsychotics, clonidine, and valproic acid may provide benefit for specific patient populations. As more evidence emerges, these agents may start playing a greater role in the management of agitation, which is not amenable to first-line agents. As health care professionals, it is prudent to be familiar with their dosing regimens, common adverse effects, and the monitoring required to maximize patient benefits and minimize harms.

Systematic Review and Meta-Analysis of Acute Kidney Injury Associated with Concomitant Vancomycin and Piperacillin/tazobactam.

Concomitant vancomycin and piperacillin/tazobactam may be associated with increased acute kidney injury (AKI) compared to vancomycin without piperacillin/tazobactam. A systematic search of Medline, Cochrane Library, and Scopus through October 2016 using ["vancomycin" and "piperacillin" and "tazobactam"] and ["AKI" or "acute renal failure" or "nephrotoxicity"] and registered meta-analysis (PROSPERO: CRD42016041646) with relevant scenarios was performed. From 307 results, fourteen observational studies totaling 3549 patients were analyzed. Concomitant vancomycin and piperacillin/tazobactam was associated with AKI in unadjusted (odds ratio (OR) 3.12, 95% confidence interval (CI) 2.04-4.78) and adjusted (aOR 3.11, 95% CI 1.77-5.47) analyses. Similar findings were seen assessing studies in adults (aOR 3.15, 95% CI 1.72-5.76), children (OR 4.55, 95% CI 2.71-10.21), and when <50% of patients received care in an intensive care unit (aOR 3.04, 95% CI 1.49-6.22) but not ≥50% (aOR 2.83, 95% CI 0.74-10.85). Increased AKI with concomitant vancomycin and piperacillin/tazobactam should be considered when determining beta-lactam therapy.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal polymerase chain reaction assay in critically ill patients with nosocomial pneumonia.

PURPOSE: This study investigated the diagnostic performance characteristics of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) assay in critically ill patients with nosocomial pneumonia. MATERIALS AND METHODS: This retrospective, single-center study included adult patients admitted to an intensive care unit with suspected nosocomial pneumonia. Patients must have received an MRSA nasal PCR assay and respiratory culture within predetermined time intervals. The primary outcome included the diagnostic performance characteristics of the assay. Secondary outcomes included the change in negative predictive value (NPV) over time, rate of acute kidney injury, and cost avoidance associated with vancomycin and monitoring. RESULTS: In 400 patients meeting inclusion criteria, the prevalence of culture confirmed MRSA pneumonia was 9.3%. When compared to initial cultures, the PCR assay demonstrated 91.89% sensitivity and 84.3% specificity with a positive predictive value and NPV of 37.36% and 99.03%. The NPV decreased to 87.5% at 21.9 days. No difference was found in rates of acute kidney injury. A cost avoidance of $108 per patient was estimated in patients de-escalated based on negative results. CONCLUSION: In critically ill patients, an MRSA nasal PCR assay has a high NPV for nosocomial pneumonia and can be used to guide vancomycin de-escalation.

Comparative Incidence of Acute Kidney Injury in Critically Ill Patients Receiving Vancomycin with Concomitant Piperacillin-Tazobactam or Cefepime: A Retrospective Cohort Study.

STUDY OBJECTIVE: The combination of vancomycin and piperacillin-tazobactam has been associated with an increased risk of acute kidney injury (AKI) in non-critically ill patient populations, but it is still unknown if this association exists in critically ill patients. The objective of this study was to compare the incidence of AKI development during therapy or within 72 hours after completion of therapy in adult critically ill patients who received vancomycin with concomitant piperacillin-tazobactam or cefepime. DESIGN: Retrospective cohort study. SETTING: Medical, surgical, and neuroscience intensive care units (ICUs) within a single tertiary care hospital. PATIENTS: A total of 122 critically ill patients who received at least 48 hours of combination therapy with vancomycin and piperacillin-tazobactam (49 patients) or vancomycin and cefepime (73 patients) during an ICU admission between September 2012 and December 2014. MEASUREMENTS AND MAIN RESULTS: The primary outcome was AKI development, as determined by the Acute Kidney Injury Network criteria, during combination therapy or within 72 hours of completion of combination therapy. The inverse probability of the treatment-weighting (IPTW) approach was used to account for potential treatment selection bias. AKI incidence was assessed in the unadjusted and propensity score-weighted cohorts. Of the 122 patients, 37 patients (30.3%) developed AKI. In the unadjusted analysis, the incidence of AKI was similar in the piperacillin-tazobactam group compared with the cefepime group (32.7% vs 28.8%, p=0.647). The average treatment effect between the groups was not significant, showing no association between ß-lactam choice and AKI (ß = -0.004, p=0.958). Secondary outcomes were ICU length of stay, hospital length of stay, AKI duration, and need for renal replacement therapy. The choice of ß-lactam was not a significant predictor of any of these outcomes: ICU length of stay (ß = 0.436, p=0.780), hospital length of stay (ß = 3.819, p=0.125), AKI duration (ß = -4.027, p=0.283), and need for renal replacement therapy (ß = 2.828, p=0.161). CONCLUSION: After adjusting for propensity to receive each of the treatment choices, no significant difference was found in the incidence of AKI development or other outcomes between the groups. The previously described finding that concomitant vancomycin and piperacillin-tazobactam increases AKI in non-critically ill patients may not be generalizable to the critically ill population. Prospective evaluation of this hypothesis is warranted.