Multicenter study evaluating target attainment of anti-Factor Xa levels using various enoxaparin prophylactic dosing practices in adult trauma patients.

STUDY OBJECTIVE: Enoxaparin is standard of care for venous thromboembolism (VTE) prophylaxis in adult trauma patients, but fixed-dose protocols are suboptimal. Dosing based on body mass index (BMI) or total body weight (TBW) improves target prophylactic anti-Xa level attainment and reduces VTE rates. A novel strategy using estimated blood volume (EBV) may be more effective based on results of a single-center study. This study compared BMI-, TBW-, EBV-based, and hybrid enoxaparin dosing strategies at achieving target prophylactic anti-Factor Xa (anti-Xa) levels in trauma patients. DESIGN: Multicenter, retrospective review. DATA SOURCE: Electronic health records from participating institutions. PATIENTS: Adult trauma patients who received enoxaparin twice daily for VTE prophylaxis and had at least one appropriately timed anti-Xa level (collected 3 to 6 hours after the previous dose after three consecutive doses) from January 2017 through December 2020. Patients were excluded if the hospital-specific dosing protocol was not followed or if they had thermal burns with > 20% body surface area involvement. INTERVENTION: Dosing strategy used to determine initial prophylactic dose of enoxaparin. MEASUREMENTS: The primary end point was percentage of patients with peak anti-Xa levels within the target prophylactic range (0.2-0.4 units/mL). MAIN RESULTS: Nine hospitals enrolled 742 unique patients. The most common dosing strategy was based on BMI (43.0%), followed by EBV (29.0%). Patients dosed using EBV had the highest percentage of target anti-Xa levels (72.1%). Multiple logistic regression demonstrated EBV-based dosing was significantly more likely to yield anti-Xa levels at or above target compared to BMI-based dosing (adjusted odds ratio (aOR) 3.59, 95% confidence interval (CI) 2.29-5.62, p < 0.001). EBV-based dosing was also more likely than hybrid dosing to yield an anti-Xa level at or above target (aOR 2.30, 95% CI 1.33-3.98, p = 0.003). Other pairwise comparisons between dosing strategy groups were nonsignificant. CONCLUSIONS: An EBV-based dosing strategy was associated with higher odds of achieving anti-Xa level within target range for enoxaparin VTE prophylaxis compared to BMI-based dosing and may be a preferred method for VTE prophylaxis in adult trauma patients.

Multicenter Retrospective Review of Ketamine Use in the ICU.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established. OBJECTIVES: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium. DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017. MAIN OUTCOMES AND MEASURES: Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after. RESULTS: A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation (n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study. CONCLUSIONS AND RELEVANCE: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased.

Evaluation of Linezolid Pharmacokinetics in Critically Ill Obese Patients with Severe Skin and Soft Tissue Infections.

Linezolid standard dosing is fixed at 600 mg every 12 h (q12h) for adults. Literature suggests critically ill, obese patients require higher doses. The study aim is 2-fold: (i) to describe linezolid pharmacokinetics (PK), and (ii) to evaluate if PK/pharmacodynamic (PD) target attainment is achieved with standard dosing in critically ill, obese patients with severe skin and soft tissue infections (SSTIs). Adult patients with a body mass index (BMI) of ≥30 kg/m2 and receiving intravenous (i.v.) linezolid from August 2018 to April 2019 were eligible for consent in this prospective study. Severe SSTIs were defined as necrotizing fasciitis, myonecrosis, or SSTI with sepsis syndrome. Four blood samples were collected at steady state at 1, 3, 5 h postinfusion and as a trough. Target attainment was defined as achieving area under the concentration-time curve from 0 to 24 h to MIC (AUC0-24h/MIC) of ≥100 h*mg/liter. Monte Carlo simulations were used to determine the probability of target attainment (PTA). Eleven patients were included in the study. The median BMI was 45.7 kg/m2, and median total body weight (TBW) was 136.0 kg. Seven patients received standard linezolid doses, and four received 600 mg q8h. A one-compartment model described linezolid PK. Based on AUC0-24h/MIC targets, for noncirrhotic patients at 140 kg, the PTA with standard linezolid doses was 100%, 98.8%, 34.1%, and 0% for MICs of 0.5, 1, 2, and 4 mg/liter, respectively. In conclusion, target attainment of ≥90% is not achieved with standard linezolid doses for noncirrhotic patients ≥140 kg with MICs of ≥2 mg/liter. This study adds to accumulating evidence that standard linezolid doses may not be adequate for all patients.

Impact of Ketamine Use on Adjunctive Analgesic and Sedative Medications in Critically Ill Trauma Patients.

BACKGROUND: Ketamine may be used to manage pain and agitation that is refractory to what are usually considered traditional agents such as fentanyl, propofol, benzodiazepines, and dexmedetomidine; however, literature describing the use of ketamine continuous infusions for this purpose in critically ill trauma patients is limited. OBJECTIVES: The primary objective of this study was to determine the impact of the initiation of a ketamine continuous infusion on sedative and analgesic use in critically ill trauma patients. Secondary objectives were to identify the patient population in which ketamine was initiated, assess the proportion of time patients were at their goal level of sedation, and determine the dosing patterns of adjunctive sedative agents. METHODS: This single-center retrospective chart review over a 19-month period included critically ill mechanically ventilated adult trauma patients in whom a ketamine continuous infusion was initiated for management of sedation and agitation. Patients who received ketamine for other indications or by the acute pain management service were not included in this evaluation. RESULTS: Thirty-six patients were included in the study. Patients in whom ketamine was initiated tended to be white men with blunt trauma. Overall, the initiation of ketamine was associated with a decrease in the amount of opioids and propofol used and an increase in the amount of ziprasidone and dexmedetomidine needed to achieve the goal Richmond Agitation Sedation Score. When compared with the time period before ketamine initiation, the proportion of time that patients achieved goal sedation was not significantly different after the addition of ketamine. CONCLUSIONS: Although the use of ketamine in critically ill mechanically ventilated adult trauma patients was associated with decreased opioid use, it was also associated with increased use of dexmedetomidine and ziprasidone to achieve and maintain sedation. Further examination of clinical outcomes associated with these differences in drug use in a larger population of trauma patients is warranted before routine use of ketamine for analgesia and sedation can be recommended.