Evaluating the Risk of Developing Thrombocytopenia Within Five Days of Continuous Renal Replacement Therapy Initiation in Septic Patients.

BACKGROUND: The differential diagnosis for thrombocytopenia in critical illness is often extensive. This study was performed to determine the incidence of thrombocytopenia in septic patients undergoing continuous renal replacement therapy (CRRT) versus those not undergoing CRRT. OBJECTIVE: The primary outcome of this study was to compare the development of thrombocytopenia, defined as a platelet count ≤ 100 × 103/mm3, in septic patients within 5 days of time zero. Time zero was defined as the baseline platelet count upon hospital admission or CRRT initiation. METHODS: An IRB approved, retrospective cohort study was conducted evaluating thrombocytopenia development in critically ill, septic patients who were initiated on CRRT versus those whom were not. Baseline and clinical characteristics were displayed using descriptive statistics. The primary outcome was evaluated overall and in subgroups of CRRT using Chi-square tests. RESULTS: One hundred sixty patients, 80 per arm, were included in the study. Thrombocytopenia development within 5 days occurred more frequently in the renal replacement therapy (RRT) group compared to the control group (67.5% vs. 6.3%, p < 0.001). In the subgroup analysis of the RRT cohort, thrombocytopenia development within 5 days occurred more frequently in the continuous veno-venous hemofiltration (CVVH) group compared to the accelerated veno-venous hemofiltration (AVVH) group (76% vs. 53.3%, p = 0.049). CONCLUSION: There is a high likelihood that septic patients initiated on CRRT will develop thrombocytopenia during their hospital stay. Patients receiving CVVH may develop thrombocytopenia more frequently than those receiving AVVH. Overall, CRRT should remain a differential diagnosis for thrombocytopenia development in this patient population.

PHarmacist Avoidance or Reductions in Medical Costs in CRITically Ill Adults: PHARM-CRIT Study.

To comprehensively classify interventions performed by ICU clinical pharmacists and quantify cost avoidance generated through their accepted interventions. DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019. SETTING: Community hospitals and academic medical centers in the United States. PARTICIPANTS: ICU clinical pharmacists. INTERVENTIONS: Recommendations classified into one of 38 intervention categories (divided into six unique sections) associated with cost avoidance. MEASUREMENTS AND MAIN RESULTS: Two-hundred fifteen ICU pharmacists at 85 centers performed 55,926 interventions during 3,148 shifts that were accepted on 27,681 adult patient days and generated $23,404,089 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established sections was adverse drug event prevention (5,777 interventions; $5,822,539 CA), resource utilization (12,630 interventions; $4,491,318), individualization of patient care (29,284 interventions; $9,680,036 cost avoidance), prophylaxis (1,639 interventions; $1,414,465 cost avoidance), hands-on care (1,828 interventions; $1,339,621 cost avoidance), and administrative/supportive tasks (4,768 interventions; $656,110 cost avoidance). Mean cost avoidance was $418 per intervention, $845 per patient day, and $7,435 per ICU pharmacist shift. The annualized cost avoidance from an ICU pharmacist is $1,784,302. The potential monetary cost avoidance to pharmacist salary ratio was between $3.3:1 and $9.6:1. CONCLUSIONS: Pharmacist involvement in the care of critically ill patients results in significant avoidance of healthcare costs, particularly in the areas of individualization of patient care, adverse drug event prevention, and resource utilization. The potential monetary cost avoidance to pharmacist salary ratio employing an ICU clinical pharmacist is between $3.3:1 and $9.6:1.

Four-factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors versus Warfarin in Life-threatening Bleeding.

INTRODUCTION: Factor Xa (fXa) inhibitor reversal for life-threatening bleeding is controversial due to a lack of high-quality evidence. The purpose of this study was to determine the hemostatic efficacy of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of fXa inhibitors compared to warfarin for life-threatening bleeding. METHODS: This was a multicenter, retrospective cohort study at two academic medical centers between January 1, 2014-December 31, 2019, which included patients who presented to the emergency department with a life-threatening bleed necessitating anticoagulation reversal with 4F-PCC. The primary endpoint was achievement of hemostatic efficacy after 4F-PCC administration. RESULTS: Of the 525 patients who had an order for 4F-PCC during the study period, 148 patients met the criteria for inclusion (n = 48 fXa inhibitor group; n = 100 warfarin group). Apixaban (52.1%) and rivaroxaban (45.8%) were the most commonly used fXa inhibitors. Effective hemostasis was similar between groups (79.2% fXa inhibitor group vs 85% warfarin group, p = 0.38). This was consistent across all types of bleeding. Thrombotic events were rare in both groups (2% vs 3%). CONCLUSION: This multicenter, retrospective cohort study demonstrated that using 4F-PCC for treatment of life-threatening bleeding produced effective hemostasis in patients on fXa inhibitors and warfarin.

PHarmacist Avoidance or Reductions in Medical Costs in Patients Presenting the EMergency Department: PHARM-EM Study.

To comprehensively classify interventions performed by emergency medicine clinical pharmacists and quantify cost avoidance generated through their accepted interventions. DESIGN: A multicenter, prospective, observational study was performed between August 2018 and January 2019. SETTING: Community and academic hospitals in the United States. PARTICIPANTS: Emergency medicine clinical pharmacists. INTERVENTIONS: Recommendations classified into one of 38 intervention categories associated with cost avoidance. MEASUREMENTS AND MAIN RESULTS: Eighty-eight emergency medicine pharmacists at 49 centers performed 13,984 interventions during 917 shifts that were accepted on 8,602 patients and generated $7,531,862 of cost avoidance. The quantity of accepted interventions and cost avoidance generated in six established categories were as follows: adverse drug event prevention (1,631 interventions; $2,225,049 cost avoidance), resource utilization (628; $310,582), individualization of patient care (6,122; $1,787,170), prophylaxis (24; $22,804), hands-on care (3,533; $2,836,811), and administrative/supportive tasks (2,046; $342,881). Mean cost avoidance was $538.61 per intervention, $875.60 per patient, and $8,213.59 per emergency medicine pharmacist shift. The annualized cost avoidance from an emergency medicine pharmacist was $1,971,262. The monetary cost avoidance to pharmacist salary ratio was between $1.4:1 and $10.6:1. CONCLUSIONS: Pharmacist involvement in the care of patients presenting to the emergency department results in significant avoidance of healthcare costs, particularly in the areas of hands-on care and adverse drug event prevention. The potential monetary benefit-to-cost ratio for emergency medicine pharmacists is between $1.4:1 and $10.6:1.

Short Versus Extended Duration Vancomycin and Piperacillin/Tazobactam and the Incidence of Acute Kidney Injury in Noncritically Ill Patients.

BACKGROUND: Vancomycin plus piperacillin-tazobactam (VPT) is a commonly used empiric combination of antimicrobials. Recently, studies have demonstrated an increase in acute kidney injury (AKI) associated with combination therapy of VPT. However, the majority of studies required patients to be on VPT for a minimum of 48 to 72 hours to be considered for inclusion and had extended treatment durations longer than most empiric, short course regimens. OBJECTIVE: To assess the incidence of AKI in noncritically ill patients being treated with VPT for short-courses (24 to 60 hours) compared to patients receiving extended-courses (72 hours to 7 days). METHODS: This was a retrospective cohort study comparing the incidence of AKI in noncritically ill patients receiving VPT for short and extended durations between January 2016 and August 2018. Fishers exact tests were used for differences in nominal data between groups and Mann-Whitney U tests were used for continuous data. RESULTS: Of the 2567 screened, 154 patients were included in the short-course group and 106 were included in the extended-course group. The incidence of AKI for patients in the short-course group was 12% (19/154) versus 26% (28/106) in the extended-course group (odds ratio: 2.55, 95% CI: 1.33-4.87; P = .004). CONCLUSION: In noncritically ill patients, a short-course of VPT experienced less AKI compared to an extended-course. Clinicians should continue to practice strict antimicrobial stewardship for VPT therapies expected to continue beyond 72 hours.

Vancomycin Dosing Practices among Critical Care Pharmacists: A Survey of Society of Critical Care Medicine Pharmacists.

INTRODUCTION: Critically ill patients and their pharmacokinetics present complexities often not considered by consensus guidelines from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Prior surveys have suggested discordance between certain guideline recommendations and reported infectious disease pharmacist practice. Vancomycin dosing practices, including institutional considerations, have not previously been well described in the critically ill patient population. OBJECTIVES: To evaluate critical care pharmacists' self-reported vancomycin practices in comparison to the 2009 guideline recommendations and other best practices identified by the study investigators. METHODS: An online survey developed by the Research and Scholarship Committee of the Clinical Pharmacy and Pharmacology (CPP) Section of the Society of Critical Care Medicine (SCCM) was sent to pharmacist members of the SCCM CPP Section practicing in adult intensive care units in the spring of 2017. This survey queried pharmacists' self-reported practices regarding vancomycin dosing and monitoring in critically ill adults. RESULTS: Three-hundred and sixty-four responses were received for an estimated response rate of 26%. Critical care pharmacists self-reported largely following the 2009 vancomycin dosing and monitoring guidelines. The largest deviations in guideline recommendation compliance involve consistent use of a loading dose, dosing weight in obese patients, and quality improvement efforts related to systematically monitoring vancomycin-associated nephrotoxicity. Variation exists regarding pharmacist protocols and other practices of vancomycin use in critically ill patients. CONCLUSION: Among critical care pharmacists, reported vancomycin practices are largely consistent with the 2009 guideline recommendations. Variations in vancomycin dosing and monitoring protocols are identified, and rationale for guideline non-adherence with loading doses elucidated.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

OBJECTIVES: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. SETTINGS: Thirty-four hospitals in the United States and Jordan. PATIENTS: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). CONCLUSIONS: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

International Survey of Thrombolytic Use for Treatment of Cardiac Arrest Due to Massive Pulmonary Embolism.

OBJECTIVES: This survey sought to characterize the national prescribing patterns and barriers to the use of thrombolytic agents in the treatment of pulmonary embolism, with a specific focus on treatment during actual or imminent cardiac arrest. DESIGN: A 19-question international, cross-sectional survey on thrombolytic use in pulmonary embolism was developed, validated, and administered. A multivariable logistic regression was conducted to determine factors predictive of utilization of thrombolytics in the setting of cardiac arrest secondary to pulmonary embolism. SETTING: International survey study. SUBJECTS: Physicians, pharmacists, nurses, and other healthcare professionals who were members of the Society of Critical Care Medicine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thrombolytic users were compared with nonusers. Respondents (n = 272) predominately were physicians (62.1%) or pharmacists (30.5%) practicing in an academic medical center (54.8%) or community teaching setting (24.6%). Thrombolytic users (n = 177; 66.8%) were compared with nonusers (n = 88; 33.2%) Thrombolytic users were more likely to work in pulmonary/critical care (80.2% thrombolytic use vs 59.8%; p < 0.01) and emergency medicine (6.8% vs 3.5%; p < 0.01). Users were more likely to have an institutional guideline or policy in place pertaining to the use of thrombolytics in cardiac arrest (27.8% vs 13.6%; p < 0.01) or have a pulmonary embolism response team (38.6% vs 19.3%; p < 0.01). Lack of evidence supporting use and the risk of adverse outcomes were barriers to thrombolytic use. Working in a pulmonary/critical care environment (odds ratio, 2.36; 95% CI, 1.24-4.52) and comfort level (odds ratio, 2.77; 95% CI, 1.7-4.53) were predictive of thrombolytic use in the multivariable analysis. CONCLUSIONS: Most survey respondents used thrombolytics in the setting of cardiac arrest secondary to known or suspected pulmonary embolism. This survey study adds important data to the literature surrounding thrombolytics for pulmonary embolism as it describes thrombolytic user characteristic, barriers to use, and common prescribing practices internationally.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Characterization of clinical knowledge and problem-solving assessments employed in postgraduate year 1 pharmacy residency interviews.

PURPOSE: Attainment of postgraduate year 1 (PGY1) residency positions has become increasingly competitive. Inclusion of clinical knowledge and problem-solving assessments in onsite interviews has increased in recent years. Characterization of these assessments is necessary for applicants to best prepare for interviews and for mentors to provide guidance. METHODS: An online survey was emailed to program directors of PGY1 pharmacy residency programs accredited by the American Society of Health-System Pharmacists (ASHP). Data were analyzed using descriptive statistics. Chi-square and Fisher's exact tests were used to compare categorical data. The Mann-Whitney U test was used to analyze nonparametric continuous data. RESULTS: Of the 221 respondents, most identified their programs as based at community (48%) or academic (39%) medical centers. Ninety percent of programs reported inclusion of clinical knowledge and problem-solving assessments in the onsite interview process. The most common assessments included asking clinical questions (70%), development of a SOAP (subjective, objective, assessment, plan) note or care plan (42%), and formal presentations that applicants prepared prior to arrival (39%). Most programs (71%) reported incorporating multiple assessments, with 2 assessments included most commonly (43%). Clinical assessment performance accounted for 10% to 25% of the overall interview score in approximately half of programs. CONCLUSION: During onsite PGY1 residency interviews, applicants must be prepared to participate in at least 1 clinical knowledge and problem-solving assessment, including answering clinical questions, developing a SOAP note or care plan, and/or delivering a presentation. Applicants should expect that these assessments will account for a substantial portion of the interview evaluation.

The effect of grit on postgraduate year-one pharmacy residents' pursuit of additional training.

INTRODUCTION: Although much is known about the perceived motivating factors and barriers to individuals pursuing postgraduate year-one (PGY1) residency training, determinants for pursuit of further training after PGY1 are unclear. METHODS: Residents at accredited programs were surveyed regarding grit, residency program and resident characteristics, and pursuit of additional post-graduate training (PGT) intentions and behaviors. Two respondent groups were developed: Pursued Additional PGT and Did Not Pursue Additional PGT. Grit-S scores were compared. A multivariable logistic regression was conducted to determine predictors of additional PGT pursuit. RESULTS: Of 542 participating residents (response rate 14.9%), 332 (61.3%) pursued additional PGT. Residents in the Pursued Additional PGT group scored higher in overall Grit-S (median 3.875, interquartile range (IQR) 3.5-4.25 vs. median 3.75, IQR 3.375-4.125, p = 0.0006) and perseverance of effort (median 4.25, IQR 4-4.5 vs. median 4, IQR 3.75-4.5, p = 0.008) and consistency of interest (median 3.5, IQR 3-4 vs. median 3.5, IQR 2.75-3.75, p = 0.002) domains. Residents who early committed to a PGY2 had higher Grit-S scores than those who did not (median 4, IQR 3.625-4.25 vs. median 3.875, IQR 3.375-4.125, p = 0.012). Following multivariable logistic regression analysis, Grit-S score was the only variable associated with pursuit of additional PGT (odds ratio 17.8, 95% confidence interval 1.59-199.38). CONCLUSIONS: Grit-S scores are associated with PGY1 resident decisions to pursue further PGT and to early commit to PGY2 programs.

Effect of Cefepime on Neurotoxicity Development in Critically Ill Adults With Renal Dysfunction.

BACKGROUND: Pharmacodynamic and pathophysiologic changes in critically ill adults receiving cefepime may increase the risk of adverse events. RESEARCH QUESTION: What is the impact of cefepime exposure on neurotoxicity development in critically ill adults with renal dysfunction? STUDY DESIGN AND METHODS: Critically ill adults with creatinine clearance < 60 mL/min who received cefepime for ≥ 48 hours between January 1, 2014 and July 31, 2018 were evaluated for cefepime-associated neurotoxicity (CAN) development. Higher- and lower-dose cefepime exposure groups stratified by moderate (≥ 8 g vs < 8 g in first 48 hours) or severe (≥ 4 g vs < 4 g in first 48 hours) renal dysfunction were compared. Between-group comparisons were performed using Fisher exact tests. CAN-free survival was evaluated using Kaplan-Meier curves and log-rank tests. RESULTS: Cefepime total dose in the first 48 hours was greater in the higher-dose cefepime group (3.7 ± 1.6 g vs 7.7 ± 2.2 g; P < .001). Cefepime-associated neurotoxicity occurred infrequently in both lower- (n = 108) and higher-dose (n = 92) cefepime groups (4% vs 10%, OR 2.82, 95% CI, 0.84-9.48, P = .093). The frequencies of cefepime-associated neurotoxicity were similar between lower- and higher-dose cefepime groups when moderate renal dysfunction subgroups were compared (5% vs 7%, OR 1.42, 95% CI, 0.34-5.92, P = .72) and numerically greater in the higher-dose cefepime group in the severe renal dysfunction subgroup (0 vs 16%, P = .064). Times to cefepime-associated neurotoxicity development and resolution were similar between lower- and higher-dose groups. Durations of CAN-free survival were similar between lower- and higher-dose groups. Most patients who developed cefepime-associated neurotoxicity displayed altered mental status (n = 12, 92%). INTERPRETATION: Cefepime-associated neurotoxicity is an uncommon occurrence in critically ill adults. Patients with severe renal dysfunction receiving higher-dose cefepime may be at greater risk of cefepime-associated neurotoxicity, although this requires additional investigation.

Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations.

Objective: To summarize literature evaluating vasopressin use, focusing on clinical controversies regarding initiation, dosing, and discontinuation and interaction of vasopressin with other therapies in septic shock patients. Data Sources: A PubMed English-language literature search (January 2008 to December 2019) was performed using these terms: arginine vasopressin, septic, shock, and sepsis. Citations, including controlled trials, observational studies, review articles, guidelines, and consensus statements, were reviewed. Study Selection and Data Extraction: Relevant clinical data focusing on specific controversial questions regarding the utility of vasopressin in patients with septic shock were narratively summarized. Data Synthesis: Current literature does not strongly support the use of vasopressin as a first-line initial therapy for septic shock. Additionally, there are conflicting data for weight-based dosing of vasopressin in overweight patients. Evidence for vasopressin renal protection and interaction with corticosteroids is minimal. However, vasopressin has the ability to reduce catecholamine requirements in septic shock patients and may provide a mortality benefit in specific subgroups. Discontinuation of vasopressin last, not second to last, in resolving septic shock may reduce hypotension development. Relevance to Patient Care and Clinical Practice: This review addresses specific clinical controversies that drive vasopressin use in septic shock patients in real-world practice. Conclusion: Vasopressin should remain second-line adjunct to norepinephrine to augment mean arterial pressures. Dosing should be initiated at 0.03 U/min, and higher doses offer minimal benefit. There are conflicting data on the impact of weight on vasopressin response. Studies have failed to show renal benefit with vasopressin use or an interaction with corticosteroid therapy.

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.

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.

Effects From Continuous Infusions of Dexmedetomidine and Propofol on Hemodynamic Stability in Critically Ill Adult Patients With Septic Shock.

PURPOSE: To compare the development of clinically significant hemodynamic event (ie, hypotension or bradycardia) in adults with septic shock receiving either propofol or dexmedetomidine. MATERIALS AND METHODS: A retrospective cohort study of adults with septic shock admitted to an intensive care unit (ICU) at an academic medical center between July 2013 and July 2017. RESULTS: Patients in the propofol (n = 35) and dexmedetomidine (n = 37) groups developed a clinically significant hemodynamic event at similar frequencies (31.4 vs 29.7%, P = .99). All patients with an event experienced hypotension, whereas 2 (5.4%) patients in the dexmedetomidine group also experienced bradycardia. Most patients in both groups (70% vs 90%) received an escalating sedative dose, and almost half (42.9%) in the dexmedetomidine group had the sedative dosage increased more frequently than every 30 minutes. Patients in both groups had similar ICU (24.1 vs 24.3 days, P = .98) and hospital (37.9 vs 29.7 days, P = .29) lengths of stay. There was no difference in median time to hemodynamic event between the groups (propofol 1 hour [interquartile range, IQR: 0.5-9.9] vs dexmedetomidine 2 hours [IQR: 1.5-11.1 hours], P = .85). CONCLUSION: Patients with septic shock receiving propofol or dexmedetomidine experienced similar rates of clinically significant hemodynamic events. Most patients did not experience an event and those who did most frequently did so in the first couple of hours of therapy.