A Multicenter, Retrospective Outcome Analysis of Vancomycin Area Under the Curve versus Trough-Based Dosing Strategies in Patients with Burn OR Inhalational Injuries (MONITOR).

Vancomycin is a glycopeptide antibiotic that requires close therapeutic monitoring. Prolonged exposure to elevated concentrations increases risk for serious adverse effects such as nephrotoxicity. However, sub-therapeutic concentrations may lead to bacterial resistance and clinical failure or death. The most recent Infectious Diseases Society of America (IDSA) publication regarding therapeutic monitoring of vancomycin recommends utilizing area under the curve (AUC)-based monitoring to maximize clinical success. Despite the guideline recommendation for AUC-guided dosing, many institutions still use trough-only monitoring in their practices, including those caring for patients with acute burn injuries. Following burn injury, patients are at a higher risk for infections, multi-organ failure, and pharmacokinetic alterations. The primary objective of this multi-center retrospective study is to determine optimal therapeutic monitoring of vancomycin by comparing clinical success between AUC vs. trough-based monitoring in burn patients. MONITOR was a multicenter, retrospective study of patients with thermal or inhalation injury admitted to one of 13 burn centers from 1/1/17 to 8/31/22 who received vancomycin. Demographic and clinical course data, including acute kidney injury (AKI) incidence and clinical success were obtained. Patients were evaluated for clinical success and grouped according to method of monitoring and adjusting doses: AUC vs. trough-based monitoring. Clinical success was a composite definition and lack of meeting any 1 of 5 criteria: 1) persistent infection, 2) relapse, 3) antibiotic failure (clinical worsening), 4) AKI, 5) death. Five-hundred seventeen vancomycin courses were assessed from 485 patients. There was no difference in the rate of clinical success between AUC monitored and the trough-only monitored groups. Incidence of AKI was higher in the trough-only group; however, was not statistically significant after controlling for renal function on admission, past medical history of chronic kidney disease (CKD), and concomitant nephrotoxins.

Vitamin D Deficiency Is Associated With Increased Length of Stay After Acute Burn Injury: A Multicenter Analysis.

In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis and infectious complications. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). This was a multicenter retrospective study of adult patients at 7 burn centers admitted over a 3.5-year period, who had a 25-hydroxyvitamin D concentration drawn within the first 7 days of injury. Of 1147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, P < .001), acute kidney injury (AKI) requiring renal replacement therapy (7.3 vs 1.7%, P = .009), more days requiring vasopressors (mean 1.24 vs 0.58 days, P = .008), and fewer ventilator-free days of the first 28 days (mean 22.9 vs 25.1, P < .001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, vitamin D deficiency was associated with longer LOS. In conclusion, patients with thermal injuries and vitamin D deficiency on admission have increased LOS and worsened clinical outcomes when compared with patients with nondeficient vitamin D concentrations.

Impact of initial fluid resuscitation volume on clinical outcomes in patients with heart failure and septic shock.

Background: Fluid resuscitation is a key treatment for sepsis, but limited data exists in patients with existing heart failure (HF) and septic shock. The objective of this study was to determine the impact of initial fluid resuscitation volume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with septic shock. Methods: This multicenter, retrospective, cohort study included patients with known HF (LVEF ≤50%) presenting with septic shock. Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h; <30 mL/kg or ≥30 mL/kg. The primary outcome was a composite of in-hospital mortality or renal replacement therapy (RRT) within 7 days. Secondary outcomes included acute kidney injury (AKI), initiation of mechanical ventilation, and length of stay (LOS). All related data were collected and compared between the two groups. A generalized logistic mixed model was used to assess the association between fluid groups and the primary outcome while adjusting for baseline LVEF, Acute Physiology and Chronic Health Evaluation (APACHE) II score, inappropriate empiric antibiotics, and receipt of corticosteroids. Results: One hundred and fifty-four patients were included (93 patients in <30 mL/kg group and 61 patients in ≥30 mL/kg group). The median weight-based volume in the first 6 h was 17.7 (12.2-23.0) mL/kg in the <30 mL/kg group vs. 40.5 (34.2-53.1) mL/kg in the ≥30 mL/kg group (P <0.01). No statistical difference was detected in the composite of in-hospital mortality or RRT between the <30 mL/kg group compared to the ≥30 mL/kg group (55.9% vs. 45.9%, P=0.25), respectively. The <30 mL/kg group had a higher incidence of AKI, mechanical ventilation, and longer hospital LOS. Conclusions: In patients with known reduced or mildly reduced LVEF presenting with septic shock, no difference was detected for in-hospital mortality or RRT in patients who received ≥30 mL/kg of resuscitation fluid compared to less fluid, although this study was underpowered to detect a difference. Importantly, ≥30 mL/kg fluid did not result in a higher need for mechanical ventilation.

A multicenter study analyzing the association of vitamin D deficiency and replacement with infectious outcomes in patients with burn injuries.

Vitamin D (25OHD) deficiency is associated with poor outcomes in intensive care populations. The primary objective of this 7-center study was to determine if 25OHD deficiency is associated with infectious outcomes in adult burn patients. Generalized linear mixed modeling was used to control for center effect, percent total body surface area burn (% TBSA), age, and presence of inhalation injury. A total of 1147 patients were initially included (admitted January 2016 through August 2019). After exclusions, 234 (56.8%) in the deficient (25OHD<20 ng/mL) and 178 in the non-deficient group (25OHD ≥ 20 ng/mL) remained, surpassing a priori power requirements. The non-deficient group had their concentration drawn earlier (p < 0.001), were more likely to be male (p = 0.006), Caucasian (p < 0.001), have lower body mass index (p = 0.009), lower % TBSA (p = 0.002), and taking a 25OHD supplement prior to admission (p < 0.001). Deficient patients were more likely to have an infectious outcome (52.1% vs 36.0%, p = 0.002), acute kidney injury with renal replacement therapy (p = 0.009), less ventilator free days in the first 28 days (p < 0.001), and vasopressors (p = 0.01). After controlling for center, % TBSA, age, and inhalation injury the best model also included presence of deficiency (OR 2.425 [CI 1.206-4.876]), days until 25OHD supplement initiation (OR 1.139 [CI 1.035-1.252]), and choice of cholecalciferol over ergocalciferol (OR 2.112 [CI 1.151-3.877]). To the authors' knowledge, this is the first multicenter study to evaluate the relationship between 25OHD and infectious complications in burn patients.

Assessment of fluid resuscitation on time to hemodynamic stability in obese patients with septic shock.

PURPOSE: Assess time to hemodynamic stability (HDS) in obese patients with septic shock who received <30 vs. ≥30 ml/kg of initial fluid resuscitation based on actual body weight (ABW). MATERIALS AND METHODS: Multicenter, retrospective, cohort analysis of 322 patients. RESULTS: Overall 216 (67%) patients received <30 ml/kg of initial fluid resuscitation. Initial fluid received was lower in the <30 ml/kg vs. ≥30 ml/kg group (16 vs. 37 ml/kg). The ≥30 ml/kg group had shorter time to HDS (multivariable p = 0.038) and lower riskof in-hospital death (multivariable p = 0.038). An exploratory subgroup analysis (n = 227) was performed, classifying patients by dosing strategy [ABW, adjusted body weight (AdjBW), ideal body weight (IBW)] based on fluid received at 3 h divided by 30 ml/kg. ABW dosed patients had a shorter time to HDS (multivariable p = 0.013) and lower risk of in-hospital death (multivariable p = 0.008) vs. IBW. Similar outcomes were observed between ABW vs. AdjBW. CONCLUSIONS: Obese patients given ≥30 ml/kg based on ABW had a shorter time to HDS and a lower risk of in-hospital death. Exploratory results suggest improved outcomes resuscitating by ABW vs. IBW; ABW showed no strong benefit over AdjBW. Further prospective studies are needed to confirm the optimal fluid dosing in obese patients.