Extravasation is the leakage of intravenous solutions into surrounding tissues, which can be influenced by drug properties, infusion techniques, and patient-related risk factors. Although peripheral administration of vesicants may increase the risk of extravasation injuries, the time and resources required for central venous catheter placement may delay administration of time-sensitive therapies. Recent literature gathered from the growing use of peripheral vasopressors and hypertonic sodium suggests low risk of harm for initiating these emergent therapies peripherally, which may prevent delays and improve patient outcomes. Physiochemical causes of tissue injury include vasoconstriction, pH-mediated, osmolar-mediated, and cytotoxic mechanisms of extravasation injuries. Acidic agents, such as promethazine, amiodarone, and vancomycin, may cause edema, sloughing, and necrosis secondary to cellular desiccation.Alternatively, basic agents, such as phenytoin and acyclovir, may be more caustic due to deeper tissue penetration of the dissociated hydroxide ions. Osmotically active

Study Objective: Although fluid resuscitation is recommended by the Society of Critical Care Medicine Surviving Sepsis Campaign Guidelines, risks of volume overload persist.The objective of this systematic review is to assess the effects of a restrictive fluid resuscitation approach in the septic patient both during and after the initial resuscitation period (30 ml/kg).Design: A systematic review and meta-analysis with trial sequential analysis (TSA) of randomized controlled trials was conducted. Two blinded reviewers independently assessed and included studies that evaluated adult patients with sepsis involving a comparator group with an effective restrictive fluid resuscitation approach. The primary outcome was mortality. Secondary outcomes included rates of acute kidney injury (AKI), renal replacement therapy (RRT), ventilator days, intensive care unit (ICU) and hospital length of stay (LOS), duration of vasopressor therapy, and limb (or digital) ischemia.Setting: PubMed and Medline databases were queried for the search.Patients: A total of eight trials in 2375 patients were included.Intervention: Effective restrictive fluid resuscitation compared with standard of care. Measurements and Main Results:The risk of bias was high in six studies and low in two studies, and all studies implemented fluid restriction after a 30-ml/kg infusion of fluids. Fluid restriction did not significantly reduce mortality in all studies compared to usual care (37% vs. 40% with usual care; risk ratio [RR] 0.90, 95% confidence interval [CI] 0.76-1.06, p = 0.23, I 2 = 24%) or by TSA findings. There were no significant differences in rates of AKI or RRT (5 studies), LOS in ICU (4 studies) or hospital (3 studies), duration of vasopressor therapy (6 studies), or incidence of limb or digital ischemia (3 studies).However, fluid restriction significantly reduced ventilator days as evaluated in seven studies (mean difference − 1.25 days, 95% CI −1.92 to −0.58 days, p = 0.0003, I 2 = 90%). Conclusion:This study demonstrated that a restrictive resuscitation strategy in sepsis resulted in no difference in mortality but may reduce ventilator days. Larger randomized trials are required to determine the optimal management of fluids in patients with sepsis.

Background Data are limited regarding use of piperacillin/tazobactam for ESBL urinary tract infections (UTIs). The objective of this study was to compare clinical outcomes of patients treated empirically with piperacillin/tazobactam versus carbapenems for ESBL UTIs. Methods This retrospective, observational, propensity score-matched study evaluated adults with an ESBL on urine culture. Patients who had UTI symptoms or leukocytosis, and who received a carbapenem or piperacillin/tazobactam empirically for at least 48 h were included. The primary outcome was clinical success within 48 h, defined as resolution of temperature (36–38°C), resolution of symptoms or leukocytosis (WBC <12 × 103/μL) in the absence of documented symptoms, and the absence of readmission for an ESBL UTI within 6 months. Secondary outcomes included time to clinical resolution, hospital length of stay, and in-hospital and 30 day all-cause mortality. Results Overall, 223 patients were included in the full cohort and 200 patients in the matched cohort (piperacillin/tazobactam = 100, carbapenem = 100). Baseline characteristics were similar between the groups. There was no difference in the primary outcome of clinical success between the carbapenem and piperacillin/tazobactam groups (58% versus 56%, respectively; P = 0.76). Additionally, there was no difference in median (IQR) time to clinical resolution [38.9 h (21.5, 50.9 h) versus 40.3 h (27.4, 57.5 h); P = 0.37], in-hospital all-cause mortality (3% versus 3%; P = 1.00), or 30 day all-cause mortality (4% versus 2%; P = 0.68) between the carbapenem and piperacillin/tazobactam groups, respectively. Conclusions There was no significant difference in clinical success for patients treated empirically with piperacillin/tazobactam compared with carbapenems for ESBL UTIs.

Background While literature supports use of carbapenems over piperacillin-tazobactam (TZP) for extended spectrum beta-lactamase (ESBL) bacteremia, data is limited regarding the use of TZP for ESBL urinary tract infections (UTIs). The objective of this study is to determine if patients have similar clinical outcomes when empirically treated with TZP versus carbapenems for ESBL UTIs. Methods This IRB-approved, retrospective, non-inferiority study evaluated adult patients admitted to a 5-facility healthcare system from January 1, 2016 to June 30, 2021. Patients who received a carbapenem or TZP empirically for at least 48 hours with a urine culture positive for an ESBL, urinary symptoms or leukocytosis, and isolate susceptibility to the empiric antibiotic of choice were included. The primary outcome was clinical success within 48 hours defined as resolution of temperature (36-38 °C), resolution of symptoms or leukocytosis (WBC < 12 x103/μL) in the absence of symptoms, and the absence of readmission for an ESBL UTI within 6 months. Secondary outcomes included time to clinical success, hospital length of stay (LOS), and 30-day all-cause mortality. Results A total of 223 patients were included with 123 (55%) patients receiving TZP and 100 (45%) patients receiving a carbapenem. Patients were predominantly female (65%) and Caucasian (52%) with a median (IQR) age of 70 (58, 81) years. Baseline characteristics were similar between the groups with no difference in complicated cystitis (60%), pyelonephritis (27%), or concomitant bacteremia (25%) (Table 1). There was no difference in the primary outcome of clinical success between the carbapenem and TZP group (60% vs 59%, respectively; p=0.92). Additionally, there was no difference in median (IQR) time to clinical success [39 (21, 52) vs 40 (25, 57) hrs, p=0.53], median hospital LOS [7.0 (5.1, 10.6) vs 6.8 (4.7, 9.2) days, p=0.12], or 30-day all-cause mortality (4% vs 2%, p=0.72) between the carbapenem and TZP groups, respectively (Table 2). Conclusion In this large, multi-center study, we found no difference in clinical outcomes in patients with UTIs caused by ESBL-producing organisms treated empirically with TZP versus carbapenems. Clinicians could consider using TZP in patients with ESBL UTIs susceptible to TZP. Disclosures Michael S. Gelfand, MD, AbbVie: Expert Testimony|La Jolla: Expert Testimony Kerry O. Cleveland, MD, AbbVie: Honoraria|Cumberland: Honoraria|Merck: Honoraria|Pfizer: Honoraria.

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