Kevin Box

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−1infused over 10 minutes followed by 0.2–0.7 mcg kg−1 h−1continuous 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.

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.

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.

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 (Fig. 1). 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 1. Percentage of patients below, in, and above target anti-Xa levels, by dosing regimen. *Difference pre-intervention to new dosing regimen p < 0.05. 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.

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.

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.