Clinical Experience With Pharmacological Venous Thromboembolism Prophylaxis in the Underweight and Critically Ill.

BACKGROUND: The optimal regimen for pharmacological prophylaxis of venous thromboembolism (VTE) in underweight, critically ill patients is unknown. OBJECTIVE: To describe prescribing patterns for VTE prophylaxis in underweight (≤50 kg or body mass index ≤18.5 kg/m(2)), critically ill patients and identify the prevalence of VTE and bleeding. METHODS: This was a retrospective cohort study that included patients who received standard- or reduced-dose VTE prophylaxis for ≥48 hours. RESULTS: A total of 295 individuals were included in the study. The majority of underweight patients in this study (79.7%) received unfractionated heparin, 5000 units 3 times daily. No statistically significant difference in the prevalence of clinically relevant VTEs between the reduced- and standard-dose groups was observed (4.4% vs 5.6%, P = 1.00), but a higher proportion of bleeding events was identified within the standard-dose group (6.7% vs 11.2%, P = 0.4). CONCLUSIONS: Empirical dose reductions of VTE prophylaxis are infrequently used in underweight, critically ill patients. Further studies need to be conducted that assess the safety and efficacy of reduced-dose VTE prophylactic regimens in this population to determine if acceptable efficacy can be achieved, with lower risks of bleeding.

Use of a Shared Canister Protocol for the Delivery of Metered-Dose Inhalers in Mechanically Ventilated Subjects.

BACKGROUND: Mechanically ventilated patients often need bronchodilators administered via a metered-dose inhaler (MDI). Unfortunately, there are no data examining the impact of shared canister delivery of MDI therapy in mechanically ventilated patients. METHODS: A prospective trial was conducted with subjects assigned to shared canister MDI therapy or single-patient canister MDI therapy. Outcomes assessed were occurrence of ventilator-associated pneumonia (VAP), hospital mortality, length of stay, ventilator-associated events, and MDI costs. RESULTS: Among 486 screened patients, 353 were included for analysis of which 201 (56.9%) received shared canister MDI therapy and 152 (43.1%) received single-patient canister therapy. VAP (7.0% vs 4.6%, P = .35), hospital mortality (21.9% vs 20.4%, P = .73), and ventilator days (median [interquartile range] 3.1 [0.9-7.5] d vs 2.7 [1.2-7.1] d, P = .62) were similar between the shared canister and single-patient canister groups. We did not observe clinically important differences for ventilator-associated events between study groups in our logistic regression analysis (P = .07). There was a savings of $217/subject in the shared canister group due to the use of 299 fewer MDIs. CONCLUSIONS: Our study found that shared canister MDI therapy compared with single-patient MDI use was associated with a significant cost savings and similar rates of VAP, hospital mortality, and length of stay but a greater prevalence of ventilator-associated events. This finding suggests that shared canister delivery of MDIs may be a cost-effective practice in mechanically ventilated patients. Based on our findings, further studies examining the overall safety of shared canister use in mechanically ventilated patients seem warranted before recommending their routine use. (ClinicalTrials.gov registration NCT01935388.).

A prospective time-series quality improvement trial of a standardized analgesia protocol to reduce postoperative pain among neurosurgery patients.

OBJECTIVE The inclusion of the pain management domain in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey now ties patients' perceptions of pain and analgesia to financial reimbursement for inpatient stays. Therefore, the authors wanted to determine if a quality improvement initiative centered on a standardized analgesia protocol could significantly reduce postoperative pain among neurosurgery patients. METHODS The authors implemented a 10-month, prospective, interrupted time-series trial of a quality improvement initiative. The intervention consisted of a multimodal, interdepartmental, standardized analgesia protocol with process improvements from preadmission to discharge. All neurosurgical-floor patients participated in the quality improvement intervention, with data collected on a systematically randomly sampled subset of 96 patients for detailed analysis. Patient-reported numeric rating scale pain on the first postoperative day (POD) served as the primary outcome. RESULTS Implementation of the analgesia protocol resulted in improved preoperative and postoperative documentation of pain (p < 0.001) and improved use of multimodal analgesia, including use of NSAIDs (p < 0.009) and gabapentin (p < 0.027). This intervention also correlated with a 32% reduction in reported pain on the 1st POD for all neurosurgical patients (mean pain scale scores 4.31 vs 2.94; p = 0.000) and a 43% reduction among spinal surgery patients (mean pain scale scores 5.45 vs 3.10; p = 0.036). After controlling for covariates, implementation of the protocol was a significant predictor of lowered postoperative pain (p = 0.05) on the 1st POD. This reduction in pain correlated with protocol compliance (p = 0.028), and a significant decrease in the monthly number of naloxone doses suggests improved safety (mean dose ± SD 1.5 ± 1.0 vs 0.33 ± 0.5; p = 0.04). Furthermore, a significant and persistent reduction in the pain management component of the HCAHPS scores suggests a durability of results extending beyond the life of the study (72.1% vs 82.0%; p = 0.033). CONCLUSIONS The implementation of a standardized analgesia protocol can significantly reduce postoperative pain among neurosurgical patients while increasing safety. Given the current climate of patient-centered outcomes, this study has broad implications for the continuum of care model proposed in the Affordable Care Act. Clinical trial registration no.: NCT01693588 ( clincaltrials.gov ).

Clinical experience with prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment or renal failure requiring renal replacement therapy.

BACKGROUND: Fondaparinux has an increased bleeding risk in patients with a CrCl ≤ 50 mL/min and is contraindicated if CrCl < 30 mL/min. Data regarding dosing and anti-Xa monitoring are lacking in this population. OBJECTIVE: To describe dosing, monitoring, and safety outcomes of prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment, including renal replacement therapy (RRT). METHODS: Retrospective analysis from October 2006 to November 2012 of patients ≥ 18 years old who received fondaparinux for ≥ 72 hours with ≥ 1 dose in an intensive care unit and a CrCl ≤ 50 mL/min or RRT during therapy. Participants were divided into 4 cohorts: moderate impairment (CrCl = 30-50 mL/min), severe impairment (CrCl < 30 mL/min), hemodialysis (HD), or continuous venovenous hemofiltration (CVVH). Outcomes included the incidence of clinically significant bleeding and thromboembolic events. Fondaparinux dose, dosing frequency, and anti-Xa level monitoring are described. Pharmacokinetic modeling was performed to assess drug accumulation. RESULTS: In all, 95 patients met inclusion criteria: 64 (67.4%) with moderate impairment, 10 (10.5%) with severe impairment, 5 (5.3%) with HD, and 16 (16.8%) with CVVH. The median defined daily doses in the moderate, severe, HD, and CVVH cohorts were 2.5, 2.5, 0.9, and 1.9 mg. Anti-Xa monitoring occurred in 19 (20%) patients, although few concentrations were peaks. Clinically significant bleeding occurred in 4 (4.2%) patients. A pharmacokinetic model demonstrated drug accumulation. CONCLUSIONS: Empirical dose adjustments may be prudent in critically ill patients with renal dysfunction; however, the optimal fondaparinux dosage in this population remains unknown. Peak anti-Xa concentrations may help guide therapy.

Seizure prophylaxis in neurocritical care: a review of evidence-based support.

Seizures are a well-described complication of acute brain injury and neurosurgery. Antiepileptic drugs (AEDs) are frequently utilized for seizure prophylaxis in neurocritical care patients. In this review, the Neurocritical Care Society Pharmacy Section describes the evidence associated with the use of AEDs for seizure prophylaxis in patients with intracerebral tumors, traumatic brain injury, aneurysmal subarachnoid hemorrhage, craniotomy, ischemic stroke, and intracerebral hemorrhage. Clear evidence indicates that the short-term use of AEDs for seizure prophylaxis in patients with traumatic brain injury and aneurysmal subarachnoid hemorrhage may be beneficial; however, evidence to support the use of AEDs in other disease states is less clear.

Clinically significant venous thromboembolic complications in burn patients receiving unfractionated heparin or enoxaparin as prophylaxis.

The aim of the study is to examine the comparative effectiveness of unfractionated heparin 5000 units given subcutaneously two or three times daily and enoxaparin given 30 mg subcutaneously twice daily or 40 mg daily for the prevention of venous thromboembolism in burn patients. This is a retrospective cohort study conducted in adult burn patients admitted between January 1, 1998, and September 30, 2008, who received only one agent for prophylaxis against venous thromboembolism during their admission. The primary outcome was a symptomatic venous thromboembolism, defined as any lower extremity deep venous thrombosis or pulmonary embolism. A total of 1111 patients were included; 600 received heparin and 511 received enoxaparin. Five patients (0.45%) experienced a symptomatic venous thromboembolic event. All five events occurred in the heparin group (P = .07). Heparin patients were older, had a larger TBSA burned, and a longer length of stay. No incidences of heparin-induced thrombocytopenia were identified. In this retrospective study of burned patients, the authors report a low incidence of symptomatic venous thromboembolic events. All events occurred in patients receiving unfractionated heparin as prophylaxis; however, the number of risk factors for venous thromboembolism was also greater in this group. Future prospective studies are needed to determine definitive conclusions regarding appropriate chemical VTE prophylaxis and dosing regimens for burn patients.