Cross-Border Antibiotic Resistance Patterns in Burn Patients.

Background: Antimicrobial resistance (AMR) is a growing problem worldwide, with differences in regional resistance patterns partially driven by local variance in antibiotic stewardship. Trauma patients transferring from Mexico have more AMR than those injured in the United States; we hypothesized a similar pattern would be present for burn patients. Patients and Methods: The registry of an American Burn Association (ABA)-verified burn center was queried for all admissions for burn injury January 2015 through December 2019 with hospital length-of-stay (LOS) longer than seven days. Patients were divided into two groups based upon burn location: United States (USA) or Mexico (MEX). All bacterial infections were analyzed. Results: A total of 73 MEX and 826 USA patients were included. Patients had a similar mean age (40.4 years MEX vs. 42.2 USA) and gender distribution (69.6% male vs. 64.4%). The MEX patients had larger median percent total body surface area burned (%TBSA; 11.1% vs. 4.3%; p ≤ 0.001) and longer hospital LOS (18.0 vs. 13.0 days; p = 0.028). The MEX patients more often had respiratory infections (16.4% vs. 7.4%; p = 0.046), whereas rates of other infections were similar. The MEX patients had higher rates of any resistant organism (47.2% of organisms MEX vs. 28.1% USA; p = 0.013), and were more likely to have resistant infections on univariable analysis; however, on multivariable analysis country of burn was no longer significant. Conclusions: Antimicrobial resistance is more common in burn patients initially burned in Mexico than those burned in the United States, but location was not a predictor of resistance compared to other traditional burn-related factors. Continuing to monitor for AMR regardless of country of burn remains critical.

A multicenter retrospective study evaluating the impact of desmopressin on hematoma expansion in patients with antiplatelet-associated intracranial hemorrhage.

INTRODUCTION: Antiplatelet medications interfere with hemostasis which can contribute to increased risk of hematoma expansion and potentially worse outcomes in patients presenting with intracranial hemorrhages (ICH). Current Neurocritical Care Society guidelines recommend desmopressin (DDAVP) in patients with antiplatelet-associated ICH with evidence limited by small cohorts. MATERIALS AND METHODS: Patients were included in our multi-center, retrospective study if they had computed tomographic (CT) scan confirmed ICH and were taking antiplatelet medications. Patients were excluded if hospital length of stay was <24 h, administered DDAVP dose was <0.3 µg/kg, no follow-up head CT scan was performed within the first 24 h after baseline, major neurosurgical intervention was performed in between CT scans, or the injury was an acute on chronic ICH. The primary outcome was incidence of hematoma expansion (defined as >20 % increase from baseline). Secondary outcomes were incidence of thrombotic complications within 7 days, largest absolute decrease in serum sodium within the first 24 h, and patient disposition. RESULTS: Among the 209 patients included in the study, 118 patients received DDAVP while 91 did not. The frequency of hematoma expansion was similar between patients who received DDAVP and those who did not (16.1 % vs 17.6 %; P = 0.78). No difference in secondary outcomes was observed between the two groups. CONCLUSIONS: These findings in conjunction with recently published literature may suggest minimal benefit or harm with DDAVP treatment. However, further study could elucidate any potential impact on long-term function outcomes.

One size does not fit all: Sex bias in pharmacologic venous thromboembolism prophylaxis.

BACKGROUND: The optimal enoxaparin dosing strategy to achieve venous thromboembolism (VTE) prophylaxis in trauma patients remains unclear. Current dosing guidelines often include weight, age, and renal function but still fail to achieve appropriate prophylactic anti-Xa levels in many patients. We hypothesized that additional patient factors influence anti-Xa response to enoxaparin in trauma patients. METHODS: This is a retrospective review of patients admitted to a Level 1 trauma center for ≥4 days from July 2015 to September 2020, who received enoxaparin VTE prophylaxis per protocol (50-59 kg, 30 mg/dose; 60-99 kg, 40 mg/dose; ≥100 kg, 50 mg/dose; all doses every 12 hours) and had an appropriately timed peak anti-Xa level. Multivariate regression was performed to identify independent predictors of prophylactic anti-Xa levels (0.2-0.4 IU/mL) upon first measurement. RESULTS: The cohort (N = 1,435) was 76.4% male, with a mean ± SD age of 49.9 ± 20.0 years and a mean ± SD weight of 82.5 ± 20.2 kg (males, 85.2 kg; females, 73.7 kg; p <0.001). Overall, 68.6% of patients (n = 984) had a prophylactic anti-Xa level on first assessment (69.6% of males, 65.1% of females). Males were more likely to have a subprophylactic level than females (22.1% vs. 8.0%, p <0.001), whereas females were more likely to have supraprophylactic levels than males (26.9% vs. 8.3%, p < 0.001). When controlling for creatinine clearance, anti-Xa level was independently associated with dose-to-weight ratio (odds ratio, 0.191 for 0.5 mg/kg; p < 0.001; confidence interval, 0.151-0.230) and female sex (odds ratio, 0.060; p < 0.001; confidence interval, 0.047-0.072). Weight and age were not significant when controlling for the other factors. CONCLUSION: Male patients have a decreased anti-Xa response to enoxaparin when compared with female patients, leading to a greater incidence of subprophylactic anti-Xa levels in male patients at all dose-to-weight ratios. To improve the accuracy of VTE chemoprophylaxis, sex should be considered as a variable in enoxaparin dosing models. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Insulin Infusion Computer Calculator Programmed Directly Into Electronic Health Record Medication Administration Record.

BACKGROUND: Computerized insulin infusion protocols have demonstrated higher staff satisfaction, better compliance with protocols, and increased time with glucose in range compared to paper protocols. At University of California San Diego Health (UCSDH), we implemented an insulin infusion computer calculator (IICC) and transitioned it from a web-based platform directly into the electronic medication administration record (eMAR) of our primary electronic health record (EHR). METHODS: This is a retrospective analysis of 6306 adult patients at UCSDH receiving intravenous (IV) insulin infusion from March 7, 2013 to May 30, 2019. We created three periods of the study-(1) the pre-eMAR integration period; (2) the eMAR integration period; and (3) the post-eMAR integration period-and looked at the percentage of readings within goal range (90-150 mg/dL for intensive care unit [ICU], 90-180 mg/dL for non-ICU) in patients with and without hyperglycemic emergencies. As our safety endpoints, we elected to look at incidence of blood glucose (BG) readings <70 mg/dL, <54 mg/dL, and <40 mg/dL. RESULTS: Pre-eMAR 69.8% of readings were in the 90-150 mg/dL range compared to 70.2% post-eMAR (P = .03) and 82.7% of readings were in the 90-180 mg/dL range pre-eMAR versus 82.9% (P = .09) post-eMAR in patients without hyperglycemic emergencies. Rates of hypoglycemia with BG <70 mg/dL were 0.43%, <54 mg/dL were 0.07%, and <40 mg/dL were 0.01% of readings pre- and post-eMAR. CONCLUSIONS: At UCSDH, our IICC has shown to be safe and effective in a wide variety of clinical situations and we were able to successfully transition it from a web-based platform directly into the eMAR of our primary EHR.

Cross-border antibiotic resistance patterns in trauma patients.

BACKGROUND: Antibiotic resistance is a growing problem worldwide, with differences in regional resistance patterns driven by variance in antibiotic stewardship. Hospitals along the United States-Mexico border increasingly identify resistance, raising concern for transfer of drug-resistant organisms across the border. METHODS: This retrospective review evaluated trauma admissions between March 2011 and August 2015. Patients were included if cultures were obtained during the first 3 days of hospitalization to limit analysis of hospital-acquired bacteria. A matched Mexico and US cohort subanalysis was later compared to eliminate bias in time from injury to culture. RESULTS: Among 115 Mexico and 1,149 US patients, Mexico patients were younger (mean 44.3 vs 60.4 years), had a higher median injury severity score (21 vs 10), and longer hospital durations of stay (mean 11.6 vs 5.5 days). These differences resolved in the matched analysis. Infections were more common in Mexico than US patients in the matched cohort, and resistant infections including resistant gram-negative infections were more common in Mexico patients in both the matched and overall cohorts. The only resistant organism identified in matched US patients was methicillin-resistant Staphylococcus aureus. Extended-spectrum ß-lactamase Klebsiella was found only in patients from Mexico. Additional risk factors for resistance in the matched cohorts included injury in Mexico, ≥2 days from injury to admission, and tracheostomy placement in Mexico. CONCLUSION: Antibiotic resistance is more common in patients initially treated in Mexico healthcare facilities than those treated exclusively in the United States and may require alternative empiric treatment. Global initiatives to improve antibiotic stewardship will be critical to limit the continued rise in drug-resistant infections.

Anti-Xa guided enoxaparin dose adjustment improves pharmacologic deep venous thrombosis prophylaxis in burn patients.

INTRODUCTION: Patients recovering from burn injury are at high risk of developing deep venous thrombosis (DVT). While 30-mg twice-daily enoxaparin is accepted as the standard prophylactic dose, recent evidence in injured patients suggests this dosing strategy may result in sub-optimal pharmacologic DVT prophylaxis. We hypothesized that standard enoxaparin dosing would result in inadequate DVT prophylaxis in burn patients. METHODS: A retrospective review of an ABA-verified Burn center's registry from January 2012 - December 2016 identified patients with peak plasma anti-Xa levels to monitor the efficacy of pharmacologic DVT prophylaxis. Patients ≥18 years old were included if they received at least 3 doses of enoxaparin and had appropriately timed peak anti-Xa levels. We analyzed data including patient demographics, body weight, body mass index (BMI) and total body surface area burn (TBSA). Diagnosis of DVT was collected. RESULTS: During the study period, 393 patients were screened with a plasma anti-Xa levels. Of the 157 patients that met inclusion criteria, 81 (51.6%) achieved target peak plasma anti-Xa levels (0.2-0.4 IU/mL) on standard 30-mg twice-daily prophylactic enoxaparin and 76 (48.4%) had sub-prophylactic levels. Sub-prophylactic patients were more likely to be male, have increased body weight and elevated BMI. 49 of the 76 sub-prophylactic patients received a dose-adjustment in order to reach target anti-Xa levels; 37 patients required 40mg twice-daily, 10 required 50mg twice-daily and 2 required 60mg twice-daily. The overall DVT rate was 3.8%. CONCLUSIONS: The current recommended prophylactic dose of 30-mg twice-daily enoxaparin is inadequate in many burn patients. Alternate dosing strategies should be considered to increase the number of burn patients achieving target prophylactic anti-Xa levels. Determining whether prophylactic enoxaparin dose adjustment decreases DVT rates in burn injured patients should be evaluated in future prospective trials.

If some is good, more is better: An enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis.

BACKGROUND: Empiric enoxaparin dosing is inadequate for most trauma patients, leading to below target initial anti-Xa levels and requiring dose adjustment for optimal venous thromboembolism prophylaxis. We hypothesize that patient factors affecting initial anti-Xa levels can be identified based on drug pharmacokinetics, allowing creation of a new dosing protocol that will provide a higher percentage of in-target (0.2-0.4 IU/mL) patients at initial anti-Xa level assessment. METHODS: Records of 318 trauma patients were evaluated, and NONMEM and PSN software were used to analyze 11 variables for their effects on anti-Xa levels. Computer modeling was used to select a new dosing protocol, which was implemented on the trauma service as a quality improvement project. The first 145 patients appropriately enrolled were assessed for response and complications. RESULTS: Only 29.5% of the pre-intervention group had initial anti-Xa levels in the appropriate prophylactic range (). Levels were most strongly influenced by patient weight, outweighing contributions from all other variables. A new regimen for initial dosing was therefore designed with three weight-defined categories for ease of administration. The post-intervention group showed an increase in in-target initial anti-Xa levels to 74.5% (p < 0.001), with a corresponding decrease in subprophylactic patients from 68.0% to 20.7%. There was an increase in supraprophylactic levels to 4.8%, but no supraprophylactic patients had hemorrhagic complications.(Figure is included in full-text article.) CONCLUSIONS: Implementation of a new, categorized, weight-based enoxaparin dosing protocol was safe and significantly improved the percentage of trauma patients with in-target anti-Xa levels on initial assessment. Further studies are needed to determine whether such dosing decreases venous thromboembolism rates. LEVEL OF EVIDENCE: Therapeutic/care management study, level II.

A new kid on the block: Outcomes with Kcentra 1 year after approval.

BACKGROUND: As the population ages, more trauma patients are admitted with coagulopathy. Fresh frozen plasma is effective in reversing coagulopathy caused by warfarin; however, it is not appropriate for all patients. Prothrombin complex concentrates (PCCs) are an alternative for patients who require emergent reversal, minimal-volume administration and who have a supratherapeutic international normalized ratio (INR). A four-factor PCC initially approved in Europe is now available in the United States. We sought to review our experience with Kcentra (4F-PCC) in the first year following Food and Drug Administration approval. METHODS: All trauma patients admitted to an academic Level 1 trauma center between July 15, 2013, and July 15, 2014, who received 4F-PCC for reversal of warfarin-induced coagulopathy were reviewed. 4F-PCC was given as per protocol. Univariate analysis was performed to examine patient demographics, injury characteristics, coagulation studies, 4F-PCC dose, vitamin K use, transfusions, response to reversal, duration of reversal, complications, and mortality. RESULTS: Twenty-six patients met study criteria. Of these patients, 34.6% were reversed because of intracranial hemorrhage. The mean INR decreased from 5.7 ± 6.1 (range, 1.6-30) to 1.5 ± 0.4 (range, 1.2-2.6) after 4F-PCC administration. One patient (3.8%) received concurrent fresh frozen plasma. For patients with an initial INR greater than 5.0, the mean INR decreased from 12.0 ± 8.2 to 1.6 ± 0.5. Forty-eight hours following 4F-PCC administration, mean INR for all patients remained 1.4 ± 0.4 (range, 1.0-2.6). Of the patients, 80.8% received vitamin K over this period. Fourteen patients had a pre-4F-PCC thromboelastogram; four were hypocoagulable. Two patients had repeat thromboelastograms after 4F-PCC was given, which demonstrated normal coagulation. Of the patients with intracranial hemorrhage, 66.7% showed radiographic progression of the initial insult on post-4F-PCC head computed tomography, while only 11.1% progressed clinically. In-hospital mortality was 0%. There were no thromboembolic complications. CONCLUSION: 4F-PCC effectively reverses elevated INRs in trauma patients with warfarin-induced coagulopathy, with results lasting more than 48 hours after administration. LEVEL OF EVIDENCE: Therapeutic study, level V.

High-fidelity simulation training in advanced resuscitation for pharmacy residents.

OBJECTIVE: To assess the impact of high-fidelity patient simulation on pharmacy resident knowledge, confidence, and competency with advanced resuscitation algorithms and interventions. DESIGN: An overview of the institutional cardiopulmonary arrest algorithm and a review of pertinent medications and calculations were presented to postgraduate year 1 (PGY1) pharmacy residents, followed by participation in 3 simulated clinical scenarios using a high-fidelity mannequin. ASSESSMENT: An improvement of pharmacy resident knowledge, confidence, and competency with advanced resuscitation skills was observed. In addition, pharmacy residents demonstrated high performance levels with skills requiring advanced competency and proactive interactions with the cardiac arrest team. CONCLUSION: Incorporating high-fidelity patient simulation into an advanced resuscitation training program can help pharmacy residents achieve competency through the active learning of practical skills.

Dose adjusting enoxaparin is necessary to achieve adequate venous thromboembolism prophylaxis in trauma patients.

BACKGROUND: Standard venous thromboembolism (VTE) prophylaxis with enoxaparin results in inadequate protection in certain patients, with subtherapeutic plasma anti-Xa levels associated with elevated VTE rates. We hypothesized that many trauma patients would be subtherapeutic on the standard prophylactic dose of enoxaparin. Our goal was to adjust the enoxaparin dose to achieve target anti-Xa levels to take advantage of the drug based on its pharmacologic properties. METHODS: Patients admitted to the trauma service were included if they received at least three doses of prophylactic enoxaparin and underwent at least two screening venous duplex. Peak plasma anti-Xa levels of 0.2 IU/mL or less were considered low, and the dose was increased by 10 mg twice daily until adequate anti-Xa levels were obtained. A strict screening venous duplex protocol was followed. Patients were excluded if they were diagnosed with a deep venous thrombosis before beginning enoxaparin or did not have correctly timed anti-Xa levels. RESULTS: Sixty-one trauma patients met inclusion criteria. There were three patients diagnosed with VTE (4.9%). Patients had a mean age of 45.9 years and were predominantly male (70.5%). Of the 61 patients, 18 (29.5%) had therapeutic anti-Xa levels on standard enoxaparin 30 mg twice daily. Compared with patients who had therapeutic anti-Xa levels on enoxaparin 30 mg twice daily, the 43 patients (70.5%) who were subtherapeutic were more likely to be male, have greater body weight, and larger body surface area. There were no significant bleeding events in the group that received an enoxaparin dose adjustment. CONCLUSION: Most patients had subtherapeutic anti-Xa levels while on enoxaparin 30 mg twice daily, suggesting inadequate VTE prophylaxis. The need for routine use of a higher dose of prophylactic enoxaparin in trauma patients and the effects of routinely dose adjusting enoxaparin on VTE rates should be the study of future prospective, randomized trials. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Computerized insulin infusion programs are safe and effective in the burn intensive care unit.

Glucose control has repeatedly been shown to influence favorable outcomes in the surgical intensive care unit (ICU). Intensive insulin therapy has recently been associated with reduced infections complications in burn patients. However, traditional protocols are associated with rates of severe hypoglycemia as high as 19%. Two commercial computer glucose control programs have reported rates of severe hypoglycemia (glucose <50 mg/dl) of 0.6 and 0.4%. Recently, the authors' burn ICU adopted an intensive insulin computer-based protocol created at their institution and already successfully in use in their surgical ICU. The authors hypothesized that their protocol can be used effectively in the burn patient population without an increase risk of severe hypoglycemia. All patients admitted to the burn ICU have blood glucose (BG) values checked routinely. With two consecutive hyperglycemic values >200 mg/dl, patients are placed on a computer-based protocol intravenous insulin drip. Once initiated, BGs are tested hourly with adjustments made according to the computer protocol. Values recorded from January to December 2008 were abstracted from the database and analyzed. Thirty-one patients were treated using the computer glucose control protocol and 12,699 measurements were performed. There were eight measurements <50 mg/dl (0.07%). Seventy-six percent of values were within the target range of 90 to 150 mg/dl. Few patients had severe hyperglycemia with BG >300 mg/dl (0.2%). There were no adverse events associated with the hypoglycemic episode. The computer-based protocol is more effective than those previously used at the institution and provides safe, reliable results in the burn patients.

Maintaining glycemic control when transitioning from infusion insulin: a protocol-driven, multidisciplinary approach.

BACKGROUND: An observational pilot study of 41 medical and surgical intensive care patients on infusion insulin at our own institution found that glycemic control rapidly deteriorated within 48 hours of stopping infusion insulin. This prompted the design and testing of a transition protocol. METHODS: The transition protocol identified appropriate patients for subcutaneous (SC) insulin along with the insulin dose and schedule. A pharmacist-hospitalist improvement team offered protocol guidance but adherence was left to the discretion of the provider. The primary endpoints were mean blood glucose the first and second day after stopping the insulin infusion and the number of patients with hypoglycemia (41-70 mg/dL) and severe hypoglycemia (<40 mg/dL) during the 48-hour transition. Secondary endpoints include severe hyperglycemia (>300 mg/dL), length of stay (LOS), re-initiation of the infusion insulin, day-weighted glucose mean 12 days following transition for patients with diabetes, and identification of a new diagnosis of diabetes. RESULTS: Patients with diabetes transitioned by protocol (n = 33) had better glycemic control than those (n = 39) transitioned without the protocol (Day 1 population glucose mean of 168 mg/dL vs. 211 mg/dL [P<0.001], Day 2 means of 176 mg/dL vs 218 mg/dL [P<0.001]). Severe hypoglycemia occurred once in each group. There were 14 patients newly diagnosed with diabetes based on an A1c ≥6%. Patients with stress hyperglycemia maintained good glycemic control with correctional insulin only. CONCLUSION: Protocol adherence improved glycemic control, reduced unnecessary use of insulin, and identified patients with previously undiagnosed diabetes, without any increase in hypoglycemia.

Stability of levothyroxine sodium 0.4 microg/mL in 0.9% sodium chloride injection.

CONTEXT: Intravenous levothyroxine therapy decreases vasopressor requirements and prevents cardiovascular collapse in hemodynamically unstable patients eligible for organ donation. The stability of levothyroxine when used in this manner is unknown. OBJECTIVE: To determine the stability of levothyroxine solution for intravenous use at a concentration of 0.4 microg/mL diluted in 0.9% sodium chloride. DESIGN: Triplicate sample sets were prepared by reconstituting levothyroxine 200 microg for injection with 5 mL of 0.9% sodium chloride with further dilution in 500 mL of 0.9% sodium chloride. One sample set was protected from light and the other was left unprotected. Both sample sets were stored at room temperature, and samples from each were analyzed for initial concentration and 4, 8, 12, and 24 hours later. CONCLUSIONS: Levothyroxine sodium 0.4 microg/mL in 500 mL 0.9% sodium chloride is stable for 24 hours at room temperature when protected from light.

Safety and efficacy of dexmedetomidine in neurosurgical patients.

PRIMARY OBJECTIVE: Very little information regarding effects on ICP, CPP and the safety of dexmedetomidine in neurosurgical patients has been published. The objective of this study is to gather information on the dosage, sedative effects and adverse effects of dexmedetomidine in neurosurgical patients. RESEARCH DESIGN: The study design was retrospective and descriptive. METHODS AND PROCEDURES: Computerized data were collected from the records of 39 neurosurgical patients in the ICU who received dexmedetomidine between October 2001 and December 2004. MAP, SBP, DBP, HR, ICP and CPP were recorded. The parameter means and standard deviations were obtained and plotted against time. EXPERIMENTAL INTERVENTIONS: Dexmedetomidine, an alpha-2 agonist, provides adequate sedation without altering respiratory drive, while facilitating frequent neurological examinations. The FDA approved a dosage range for a loading infusion of 0.1 mcg kg-1 infused over 10 minutes followed by 0.2-0.7 mcg kg-1 h-1 continuous infusion for 24 hours. MAIN OUTCOMES AND RESULTS: A total of 39 patients were enrolled in the study; 26 men and 13 women. The mean age was 34 years. Of the patients enrolled in the study, 15 were successfully extubated with no adverse reactions while maintaining adequate sedation. Agitation was the predominant adverse reaction. Hypotension occurred in 10 patients. The mean CPP increased and the mean ICP decreased. The standard deviation for the means of the ICP and CPP were small and did not fluctuate as widely as the haemodynamic parameters. CONCLUSIONS: Dexmedetomidine can be a safe and effective sedative agent for neurosurgical patients. A loading infusion should be avoided and higher maintenance doses may be required to ensure adequate sedation. Further studies are necessary to establish an optimal dosage regimen.