The impact of pre-injury direct oral anticoagulants compared to warfarin in geriatric G-60 trauma patients.

PURPOSE: Pre-injury oral anticoagulants are associated with worse outcomes in geriatric (G-60) trauma patients, but there are limited data comparing warfarin with direct oral anticoagulants (DOAC). We sought to compare outcomes in G-60 trauma patients taking pre-injury DOACs vs. warfarin. METHODS: All trauma patients, age ≥60 who were admitted to the hospital and taking an oral anticoagulant pre-injury were retrospectively identified. Patients were excluded if their reason for admission was a suicide attempt or penetrating extremity injury. Outcome measures included blood transfusions, hospital LOS, and mortality. A second analysis was performed, whereby patients were matched using ISS and age. RESULTS: There were 3,941 patients identified; 331 had documentation of anticoagulant use, pre-injury (warfarin, n = 237; DOAC, n = 94). Demographics were similar, but ISS [9 (4-13) vs. 8 (4-9), p = .027], initial INR [2.2 (1.8-2.9) vs. 1.2 (1.1-1.5), p < .001], and the use of pharmacologic reversal agents (48 vs. 14%, p < .001) were higher in the warfarin group. There was no difference in the use of blood transfusions (24 vs. 17%, p = .164) or mortality (5.9 vs. 4.3%, p = .789) between warfarin and DOAC groups, respectively. However, LOS was longer in the warfarin group [5 (3-7.5) vs. 4 (2-6.3) days, p = .02]. Matched analysis showed no difference in blood transfusions (23 vs. 17%, p = .276), mortality (2.1 vs. 4.3%, p = .682) or LOS [5 (3-7) vs. 4 (2-6.3) days, p = .158] between warfarin and DOAC groups, respectively. CONCLUSION: Pre-injury DOACs are not associated with worse clinical outcomes compared to warfarin in G-60 trauma patients. Higher use of pharmacologic reversal agents with warfarin may be related to differences in mechanism of action and effect on INR.

Temporal assessment of Candida risk factors in the surgical intensive care unit.

HYPOTHESIS: Risk factors for Candida infection in surgical intensive care units (SICUs) change over time. Risk factor progression may influence Candida colonization and infection. DESIGN: Multicenter cohort survey. SETTING: Three urban teaching institutions. PATIENTS: A total of 301 consecutively admitted patients in SICUs for 5 or more days. MAIN OUTCOME MEASURES: Assessment of patients on SICU days 1, 3, 4, 6, and 8 and SICU discharge for risk factors, Candida colonization, and antifungal use. Candida colonization status was categorized as noncolonized (NC), locally colonized (LC) if 1 site was involved, and disseminated infection (DI) if 2 or more sites or candidemia were involved. RESULTS: The most frequent risk factors in the 301 patients enrolled were presence of peripheral and central intravenous catheters, bladder catheters, mechanical ventilation, and lack of enteral or intravenous nutrition. Early risk factors included total parenteral nutrition or central catheter at SICU day 1 and previous SICU admissions or surgical procedures. Peak number of risk factors (mean +/- SD) were as follows: 7.2 +/- 2.6 in NC (n = 229), 9.2 +/- 2.3 in LC (n = 45), and 9.2 +/- 2.6 in DI (n = 27). These numbers were reached at day 8 in the NC and LC groups and day 4 in the DI group. The LC and DI groups had more risk factors on each SICU day than the NC group and longer median SICU length of stay (28 days in the DI group vs 11 and 19 days in the NC and LC groups, respectively). Antifungal therapy, while used most frequently in the DI group, was initiated later for this group than in NC and LC groups. CONCLUSIONS: Risk factors for Candida infection in SICU patients change over time. Patients with DI demonstrate a greater number of and more rapid increase in risk factors than patients in the LC and NC groups. Presence of early risk factors at the time of SICU admission, a high incidence of risk factors, or a rapid increase in risk factors should prompt clinicians to obtain surveillance fungal cultures and consider empirical antifungal therapy.

Medication administration errors in adult patients in the ICU.

OBJECTIVE: To quantify the incidence and specify the types of medication administration errors from a list of error-prone medications and to determine if patient harm resulted from these errors. DESIGN: An observational evaluation. SETTING: Five intensive care units (ICUs) in the United States. PATIENTS AND PARTICIPANTS: Eight hundred fifty-one patients who were at least 18 years of age and admitted to surgical, medical or mixed ICUs during a 3 month period were included. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A list of error-prone medications was adapted from the literature and evaluated for medication errors and patient harm. Of 5,744 observations in 851 patients, 187 (3.3%) medication administration errors were detected. the therapeutic classes most commonly associated with errors were vasoactive drugs 61 (32.6%) and sedative/analgesics 48 (25.7%). The most common type of error was wrong infusion rate with 71 (40.1%) errors. Twenty-one errors did not reach the patient and 159 reached the patient but did not result in harm, increased monitoring or intervention. Five errors required increased patient monitoring and two required intervention. None of the errors resulted in patient death. CONCLUSIONS: This multicenter evaluation found fewer medication administration errors than the published literature, possibly due to the varying observational techniques and pharmacist involvement. Lorazepam and wrong infusion rates are associated with errors that occurred frequently, resulted in the greatest potential for harm and were common oversights in the system. These errors should be considered potential areas for betterment in the medication use process to improve patient safety.

Population pharmacokinetics of aminoglycosides in critically ill trauma patients on once-daily regimens.

BACKGROUND: Once-daily dosing regimens of aminoglycosides are routinely used in critically ill trauma patients. However, the pharmacokinetic parameters are variable in these patients. The purpose of this study was to evaluate the pharmacokinetics of aminoglycosides in critically ill trauma patients receiving once-daily dosing regimens. METHODS: At least two aminoglycoside concentrations were measured in each patient. Population pharmacokinetic parameters were estimated on the basis of a one-compartment structural model and the program nonlinear mixed effects modeling. RESULTS: Fifty-three aminoglycoside concentrations from 19 patients were analyzed. The aminoglycoside clearance was 5.47 L/h. The mean volume of distribution was 22.2 L (0.3 L/kg). The mean half-life was 2.9 hours. Serum-aminoglycoside concentrations were undetectable for longer than 12 hours in 4 of 19 patients. Weight, age, or serum creatinine did not significantly explain the variability. CONCLUSION: There is marked variability in aminoglycoside pharmacokinetic parameters in critically ill trauma patients. This may lead to prolonged drug-free intervals. Individualized dosing of critically ill trauma patients on the basis of at least two serum-aminoglycoside concentrations seems indicated when using once-daily dosing regimens.

Treatment of hypertension in the perioperative patient.

OBJECTIVE: To review studies and drug therapy relating to the treatment of hypertension in perioperative patients. DATA SOURCES: Articles were selected from a MEDLINE search (1966-August 1998), and several textbooks on hypertension and surgery were reviewed. In addition, bibliographies of all articles and textbook chapters were studied for articles not found in the computerized searches. STUDY SELECTION: Clinical studies involving hypertension in the perioperative setting were included. The initial search was limited to studies conducted in humans and published in English. DATA EXTRACTION: Information regarding drug therapy was reviewed and guidelines were constructed for managing surgical patients with acute blood pressure elevations. DATA SYNTHESIS: Although nitroprusside and nitroglycerin, with their short onset of action and duration of effect, are indicated for hypertensive emergencies, a variety of agents are available for hypertensive urgencies. An algorithm that can be used as a template for the development of intrainstitutional guidelines is provided. CONCLUSIONS: Due to the scarcity of comparative trials, decisions involving agents for the treatment of perioperative hypertension must often be made based on combined efficacy, toxicity, cost, and convenience considerations.

A prospective study of pain control in the emergency department.

The most common complaint in the emergency department is pain. The management of acute pain, however, has not been well studied. This prospective study was designed to assess pain intensity and relief along with satisfaction in the emergency department. Adult patients with a primary complaint of acute pain were asked to complete a two-part questionnaire administered by a research assistant. The first part was completed on arrival and the second part on discharge from the emergency department. The respondents were not permitted to see the first part of the questionnaire while completing the second. The questionnaire used an unmarked, horizontal 10-cm visual analog scale along with short answer questions to measure pain, relief, and satisfaction. Choice of drug therapy was decided by the physician according to usual treatment methods. Fifty-seven people presented with the chief complaint of pain. Of those, 30 (53%) were treated with medications. The mean level of pain on admission for treated patients was 6.64 compared with a mean level of pain on discharge of 4.02 (P =.0001). Untreated patients had a mean admission visual analog scale score of 4.19. Compared with treated patients, this difference was statistically significant (P =.001). A mean visual analog scale score of 5.43, representing the mean amount of pain relief, was reported among treated patients. Treated patients also reported a visual analog scale score of 6.46 in overall satisfaction with pain management. The results of this study indicate that there is a significant and clinical difference in levels of pain and satisfaction between admission and discharge in these patients in the emergency department.

Streptokinase and urokinase for the treatment of pleural effusions and empyemas.

It is evident from these studies that thrombolytics significantly increase the amount of drainage from pleural effusions or empyemas. The effect on other outcome measures, such as length of hospital stay, days before defervescence, days with chest tube, surgical procedures, and mortality is questionable. The lack of randomized, controlled trials comparing streptokinase and urokinase makes a true comparison rather difficult. Both agents are equally effective in increasing pleural drainage. Only one comparative trial demonstrated an increased incidence of fever with streptokinase, which was reversible on discontinuation. This reaction does not occur frequently based on the results of the published literature. Overall, the low incidence of adverse reactions associated with either agent may not justify the added expense of urokinase for this indication. A majority of the clinical trials can be criticized for their low numbers of patients along with lack of control groups. It is unknown whether statistical significance would have been obtained if adequate sample sizes were used. Inclusion criteria were not uniform, as characteristics of pleural fluid and presence of loculations may influence success. Volume of drainage is also less impressive when the amount used to instill the thrombolytic is subtracted from the amount of drainage. If this were considered, statistical significance could have been altered. Finally, therapeutic end points varied throughout the literature. Most studies used volume of drainage and X-ray findings as end points. However, such surrogate markers do not necessarily correlate with clinical improvement. The optimal dose of streptokinase is 250,000 units instilled through a chest tube (which is clamped for 2-4 h) on a daily basis until decreased drainage is obtained. The optimal dose of urokinase is not known and the administration methods vary throughout the literature, ranging from 50,000 to 250,000 units. The AWP of streptokinase is $122 for 250,000 units compared with $433 for 250,000 units of urokinase. In the only comparative trial, the average number of instillations was the same, so the cost of therapy with urokinase is significantly higher. The study by Bouros et al. poses an interesting observation. They successfully treated patients with 50,000 units of urokinase, which would be approximately the same cost as streptokinase. Further studies are needed to truly evaluate the efficacy of low-dose urokinase as well as comparative trials with these two agents. In conclusion, urokinase offers no significant benefits over streptokinase. The incidence of fever was greater in one comparative trial with streptokinase than with urokinase. Based on cost considerations and lack of comparative studies, urokinase infusions should be reserved for patients who develop fever when receiving continued therapy with streptokinase.