Effectiveness of an Intravenous Insulin-Based Treatment Protocol for the Management of Hypertriglyceridemia-Associated Acute Pancreatitis.

Background: There is burgeoning interest in intravenous insulin for hypertriglyceridemia-induced acute pancreatitis (HTG-AP) as a less invasive alternative to plasmapheresis; however, there are few published descriptions of disease-specific insulin protocols. Objective: To compare the efficacy and safety of an insulin infusion-based protocol with nonstandardized medical therapy for HTG-AP. Methods: This is a retrospective analysis before and after creation of an HTG-AP-specific insulin infusion treatment protocol. Inclusion criteria were age ≥18 years, an initial triglyceride level >1000 mg/dL, and a diagnosis of AP. The primary outcome of the study was time to a triglyceride level ≤1000 mg/dL. Results: Sixty-seven patients were included in this study (26 pre-protocol and 41 in the HTG-AP insulin protocol group). Baseline characteristics between the groups were similar, with median initial triglyceride levels >3500 mg/dL. There was a trend toward patients treated with the HTG-AP-specific infusion reaching a triglyceride level ≤1000 mg/dL faster (43.3 [24.9-72.1] vs 26.9 [17.7-51.1] hours; P = 0.07). Those treated to ≤500 mg/dL achieved this faster with the disease-specific infusion (49.2 [29.4-67.8] vs 70.9 [36.3-107.2] hours, P = 0.04). Hypoglycemia was numerically lower in the HTG-AP-specific insulin infusion group despite higher insulin infusion rates (7.3% vs 19.2%). No patient in the HTG-AP-specific protocol group required plasmapheresis. Conclusions: The use of an HTG-AP-specific insulin infusion protocol, compared with antecedent nonstandardized care, resulted in prompter achievement of a triglyceride level ≤500 mg/dL and a strong trend toward faster achievement of ≤1000 mg/dL without an increased risk of hypoglycemia. While intravenous insulin may be considered the initial medical therapy for HTG-AP, further studies are needed to determine the optimal dosing.

Pre-Endoscopy Use of Proton Pump Inhibitor Intravenous Bolus Dosing in Hemodynamically Stable Patients With Suspected Upper Gastrointestinal Bleeding: Results of a Pharmacist-Managed Hospital Protocol to Reduce Continuous Infusion Pantoprazole Use.

Background: Guidelines for acute upper gastrointestinal bleeding (UGIB) recommend use of proton pump inhibitors (PPI) administered by continuous IV infusion (CI). Although data suggest comparable outcomes with CI and IV push (IVP) dosing post-endoscopy, there are limited data to support IVP PPI as the pre-endoscopy regimen. Objective: To evaluate the impact of a pharmacist-managed protocol for reducing PPI CIs and substitution of PPI IVP dosing in hemodynamically stable patients with suspected acute upper gastrointestinal bleeding (UGIB) prior to endoscopic intervention. Design, Setting, and Participants: Retrospective study; Tertiary-care community teaching hospital; Hemodynamically stable adults with confirmed or suspected UGIB. Hemodynamic stability was defined as a systolic blood pressure >90 mmHg, heart rate <100 beats, mean arterial pressure >65 mmHg, and no requirement for vasopressors. Intervention: All iterations of treatment recommendations encouraged an initial pantoprazole 80 mg IVP dose. In the pre-intervention group, patients were then treated at the at the provider's discretion with the majority receiving CI pantoprazole. After implementation of the original protocol (Phase I), all hemodynamically stable patients were allowed 1 bag of CI pantoprazole (80 mg infused over 10 hours) before being transitioned by the pharmacist to pantoprazole 40 mg IVP every 12 hours. After internal analysis, the protocol was revised to allow patients to be immediately transitioned to IVP dosing without an initial CI (Phase II). Main Outcome: Incidence of continued bleeding or re-bleeding within 7 days of initial PPI dose. Results: A total of 325 patients were included across all 3 study phases. The median number of CI bags per patient was reduced from 4 pre-intervention, to 1.5 in phase I, and to 0 in phase II (P < .001). The primary endpoint of continued bleeding or re-bleeding within 7 days was similar across all 3 groups (5.0% vs 6.5% vs 5.2%, P = .92). Mean intravenous pantoprazole costs were reduced by $21.73/patient. Conclusions: Movement toward preferential use of IVP PPI prior to endoscopy for hemodynamically stable patients with confirmed or suspected UGIBs resulted in similar rates of continued bleeding or re-bleeding and generated modest cost savings. These findings warrant further investigation.

Local Anesthetic-Induced Methemoglobinemia During Pregnancy: A Case Report and Evaluation of Treatment Options.

BACKGROUND: Methemoglobinemia is a well-recognized adverse drug reaction related to the use of certain local anesthetic agents. The mainstay of treatment for methemoglobinemia is i.v. methylene blue, along with provision of supplemental oxygen; however, methylene blue is listed as a category X teratogen. This poses an issue should methemoglobinemia develop during pregnancy. CASE REPORT: A 35-year-old, 20-week and 5-day gravid female was transferred from an outpatient oral surgeon's office for hypoxia. She was undergoing extraction of 28 teeth and was administered an unknown, but "large" quantity of prilocaine during the procedure. Given this exposure, the concern was for methemoglobinemia. This was confirmed with co-oximetry, which showed 34.7% methemoglobin. The initial treatment plan was methylene blue; however, this drug is a category X teratogen. Thus, an interdisciplinary team deliberated and decided on treatment with high-dose ascorbic acid and transfusion of a single unit of packed red blood cells. The patient was managed with noninvasive ventilation strategies and a total of 8 g ascorbic acid. She was discharged on hospital day 3 with no obstetric issues noted. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intravenous ascorbic acid appears to be a potential alternative to methylene blue in this patient population. The data surrounding teratogenicity of methylene blue are mostly related to intra-amniotic or intra-uterine administration. In life-threatening cases of methemoglobinemia during pregnancy, the benefits of i.v. methylene blue may outweigh the risks.

Nasal Methicillin-Resistant Staphylococcus aureus (MRSA) PCR Testing Reduces the Duration of MRSA-Targeted Therapy in Patients with Suspected MRSA Pneumonia.

The objective of this study was to evaluate the impact of pharmacist-ordered methicillin-resistant Staphylococcus aureus (MRSA) PCR testing on the duration of empirical MRSA-targeted antibiotic therapy in patients with suspected pneumonia. This is a retrospective analysis of patients who received vancomycin or linezolid for suspected pneumonia before and after the implementation of a pharmacist-driven protocol for nasal MRSA PCR testing. Patients were included if they were adults of >18 years of age and initiated on vancomycin or linezolid for suspected MRSA pneumonia. The primary endpoint was the duration of vancomycin or linezolid therapy. After screening 368 patients, 57 patients met inclusion criteria (27 pre-PCR and 30 post-PCR). Baseline characteristics were similar between the two groups, with the majority of patients classified as having health care-associated pneumonia (68.4%). The use of the nasal MRSA PCR test reduced the mean duration of MRSA-targeted therapy by 46.6 h (74.0 ± 48.9 h versus 27.4 ± 18.7 h; 95% confidence interval [CI], 27.3 to 65.8 h; P < 0.0001). Fewer patients in the post-PCR group required vancomycin serum levels and dose adjustment (48.1% versus 16.7%; P = 0.02). There were no significant differences between the pre- and post-PCR groups regarding days to clinical improvement (1.78 ± 2.52 versus 2.27 ± 3.34; P = 0.54), length of hospital stay (11.04 ± 9.5 versus 8.2 ± 7.8; P = 0.22), or hospital mortality (14.8% versus 6.7%; P = 0.41). The use of nasal MRSA PCR testing in patients with suspected MRSA pneumonia reduced the duration of empirical MRSA-targeted therapy by approximately 2 days without increasing adverse clinical outcomes.

Impact of an Analgesia-Based Sedation Protocol on Mechanically Ventilated Patients in a Medical Intensive Care Unit.

BACKGROUND: Recent attention to adverse effects of intensive care unit (ICU) sedation has led to the use of strategies that target a "lighter" depth of sedation. Among these strategies are "analgosedation" protocols, which prioritize pain management and preferentially use IV opioids before administration of continuously infused sedatives such as propofol or midazolam. We hypothesized that using an analgosedation protocol would result in a shorter duration of mechanical ventilation than a protocol with greater emphasis on IV sedatives METHODS: : We conducted a retrospective study comparing the duration of mechanical ventilation before and after implementation of an analgosedation protocol in a 24-bed medical ICU. Patients were aged 18 years or older and required mechanical ventilation where a light level of sedation was clinically appropriate. Exclusion criteria included a clinical need for deeper levels of sedation or tracheal intubation confined to the perioperative period. RESULTS: Seventy-nine patients were included in the postimplementation group and 65 in the preimplementation group. After adjustment for baseline covariates, introduction of the 2013 analgosedation protocol was associated with a decreased duration of mechanical ventilation (-26.62 hours; 95% confidence interval, - 44.98 to -8.26, P = 0.005). Patients managed with the analgosedation protocol experienced a lighter level of sedation (median Richmond Agitation-Sedation Scale, -2.57 vs -1.25, P = 0.001) and improved pain management (median Critical-Care Pain Observation Tool score, 2.0 vs 1.5, P = 0.03). The use of continuously infused sedatives was reduced by 54.3% (92.3% vs 38.0%, P < 0.001). CONCLUSIONS: Our findings suggest that implementation of an analgosedation protocol was associated with an overall lighter level of sedation, shorter mean ventilator duration, and a reduced use of continuous infusion sedatives. Further studies are needed to assess the impact of such protocols on ICU delirium.

Characteristics and Clinical Management of a Cluster of 3 Patients With Ebola Virus Disease, Including the First Domestically Acquired Cases in the United States.

BACKGROUND: More than 26,000 cases of Ebola virus disease (EVD) have been reported in western Africa, with high mortality. Several patients have been medically evacuated to hospitals in the United States and Europe. Detailed clinical data are limited on the clinical course and management of patients with EVD outside western Africa. OBJECTIVE: To describe the clinical characteristics and management of a cluster of patients with EVD, including the first cases of Ebola virus (EBOV) infection acquired in the United States. DESIGN: Retrospective clinical case series. SETTING: Three U.S. hospitals in September and October 2014. PATIENTS: First imported EVD case identified in the United States and 2 secondary EVD cases acquired in the United States in critical care nurses who cared for the index case patient. MEASUREMENTS: Clinical recovery, EBOV RNA level, resolution of Ebola viremia, survival with discharge from hospital, or death. RESULTS: The index patient had high EBOV RNA levels, developed respiratory and renal failure requiring critical care support, and died. Both patients with secondary EBOV infection had nonspecific signs and symptoms and developed moderate illness; EBOV RNA levels were moderate, and both patients recovered. LIMITATION: Both surviving patients received uncontrolled treatment with multiple investigational agents, including convalescent plasma, which limits generalizability of the results. CONCLUSION: Early diagnosis, prompt initiation of supportive medical care, and moderate clinical illness likely contributed to successful outcomes in both survivors. The inability to determine the potential benefit of investigational therapies and the effect of patient-specific factors that may have contributed to less severe illness highlight the need for controlled clinical studies of these interventions, especially in the setting of a high level of supportive medical care. PRIMARY FUNDING SOURCE: None.

Ebola virus disease: roles and considerations for pharmacists.

Ebola virus disease (EVD) poses significant clinical care implications for pharmacists. Emergency preparedness efforts should be undertaken to ensure vital response to EVD. Pharmacists should consider factors such as enhanced use of resources for front-line EVD patient care along with procurement of investigational medications. Appropriate and timely preparation, distribution, and administration of treatment for patients with EVD in the setting of substantial critical illness as well as infection control measures are essential. Aggressive supportive care and early, goal-directed therapy are cornerstones of therapy, whereas investigational treatments for EVD will likely play a larger, more well-defined role as future clinical trials are conducted.

Management of dabigatran-associated intracerebral and intraventricular hemorrhage: a case report.

BACKGROUND: Dabigatran is an oral, reversibly bound, direct thrombin inhibitor currently approved in the United States for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In the phase III trial leading to approval of the agent, the incidence of life-threatening bleeding was 1.80%/year in the dabigatran 150 mg twice daily arm. Because there is no direct antidote or reversal agent for this drug, the need to manage life-threatening hemorrhages with procoagulant products will arise. OBJECTIVE: To describe a case of dabigatran-associated intracerebral and intraventricular hemorrhage and subsequent management with activated prothrombin complex concentrate. CASE REPORT: An 85-year-old man currently taking dabigatran 150 mg twice daily presented to the Emergency Department for incoordination, expressive aphasia, and weakness. A computed tomography image of his head demonstrated an intracranial hemorrhage. The last dose of dabigatran was approximately 14 h prior to arrival, and conventional coagulation assays (thrombin time and activated partial thromboplastin time) confirmed the presence of dabigatran in the patient's serum. The patient received 27.5 units/kg of activated prothrombin complex concentrate (FEIBA®; Baxter Healthcare Corporation, Deerfield, IL) after an initial intravenous fluid bolus. His activated partial thromboplastin time was not completely normalized by the use of FEIBA; however, the patient's neurological examination slightly improved and remained stable throughout his hospital course despite some intraventricular expansion of the hematoma. After discharge to physical rehabilitation, the patient developed an ischemic cerebrovascular accident and was discharged home on hospice. CONCLUSION: Due to lack of an available antidote, activated prothrombin complex concentrate was utilized as a nonspecific procoagulant to stabilize an intracerebral hemorrhage in a patient on dabigatran.

A Retrospective Analysis of Intravenous Push versus Extended Infusion Meropenem in Critically Ill Patients.

Meropenem is a broad-spectrum antibiotic used for the treatment of multi-drug-resistant infections. Due to its pharmacokinetic profile, meropenem's activity is optimized by maintaining a specific time the serum concentration remains above the minimum inhibitory concentration (MIC) via extended infusion (EI), continuous infusion, or intermittent infusion dosing strategies. The available literature varies regarding the superiority of these dosing strategies. This study's primary objective was to determine the difference in time to clinical stabilization between intravenous push (IVP) and EI administration. We performed a retrospective pilot cohort study of 100 critically ill patients who received meropenem by IVP (n = 50) or EI (n = 50) during their intensive care unit (ICU) admission. There was no statistically significant difference in the overall achievement of clinical stabilization between IVP and EI (48% vs. 44%, p = 0.17). However, the median time to clinical stability was shorter for the EI group (20.4 vs. 66.2 h, p = 0.01). EI administration was associated with shorter hospital (13 vs. 17 days; p = 0.05) and ICU (6 vs. 9 days; p = 0.02) lengths of stay. Although we did not find a statistically significant difference in the overall time to clinical stabilization, the results of this pilot study suggest that EI administration may produce quicker clinical resolutions than IVP.

Acute ischemic stroke following cardioversion in a patient receiving dabigatran.

OBJECTIVE: To report a case of acute ischemic stroke following electrical cardioversion in a patient currently anticoagulated with dabigatran 150 mg twice daily. CASE SUMMARY: A 74-year-old man, who had been adherent with more than 6 weeks of dabigatran 150 mg twice daily therapy, presented with a dense left-sided hemiparesis 72 hours following a repeat electrical cardioversion. Both computed tomography and magnetic resonance angiogram confirmed a right middle cerebral artery infarct. A transesophageal echocardiogram performed after the cerebrovascular accident failed to demonstrate a cardiac source of embolus. The patient previously underwent cardioversion 4 weeks prior with no evidence at that time of thrombus or spontaneous echo contrast on transesophageal echocardiogram. DISCUSSION: Dabigatran was approved in the United States in late 2010 for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Post hoc data from the phase III trial suggest a low risk of embolism following cardioversion. Since there are no conventional coagulation measures to reliably demonstrate the level of anticoagulation in patients on dabigatran, clinicians must rely solely on patient history when assessing the safety of cardioverting a patient on this medication. Data have suggested increased pro-inflammatory mediators and increased risk of myocardial infarction with oral direct thrombin inhibitors, which may have manifested as a cerebral or carotid artery thrombosis in situ. CONCLUSION: Novel oral anticoagulants are attractive options for anticoagulation required with cardioversion. Although this case report may not preclude use of dabigatran for this purpose, it illustrates that use of this drug is not without risks. Additional investigation into the pro-inflammatory nature of the oral direct thrombin inhibitors is needed.

Effect of Peripherally Infused Norepinephrine on Reducing Central Venous Catheter Utilization.

The purpose of this retrospective study was to evaluate the impact of peripherally administered norepinephrine on avoiding central venous catheter insertion while maintaining safety of the infusion. An institutional guideline allows peripheral infusion of norepinephrine via dedicated, 16- to 20-gauge, mid-to-upper arm intravenous (IV) catheters for up to 24 hours. The primary outcome was the need for central venous access in patients initially started on peripherally infused norepinephrine. A total of 124 patients were evaluated (98 initially on peripherally infused norepinephrine vs 26 with central catheter only administration). Thirty-six (37%) of the 98 patients who were started on peripheral norepinephrine avoided the need for central catheter placement, which was associated with $8,900 in direct supply cost avoidance. Eighty (82%) of the 98 patients who started peripherally infused norepinephrine required the vasopressor for ≤12 hours. No extravasation or local complications were observed in any of the 124 patients, regardless of site of infusion. Administration of norepinephrine via a dedicated peripheral IV site appears safe and may lead to a reduction in the need for subsequent central venous access. To achieve timely resuscitation goals, as well as to minimize complications associated with central access, initial peripheral administration should be considered for all patients.

Stopping trials early for benefit--not so fast!

On October 25, 2011, Eli Lilly and Company announced the voluntary withdrawal of Xigris (drotrecogin alfa [activated]) following the negative results of its most recent clinical trial, the PROWESS-SHOCK study. The purpose of this commentary is to briefly review the history of drotrecogin alfa, discuss issues surrounding early cessation of clinical trials for benefit, and highlight the scientific and ethical dilemmas faced when deciding whether or not to stop a trial early for benefit. This review should serve as an introduction to the topic of stopping trials early for benefit.

Use of the AGREE II instrument to evaluate critical care practice guidelines addressing pharmacotherapy.

RATIONALE, AIMS AND OBJECTIVES: Clinical practice guidelines (CPGs) have been evaluated for reporting transparency and methodological quality in a number of studies in various disciplines, but few studies have focused on critical care and none on pharmacotherapy-related guidelines specifically. The objective of this study was to evaluate the quality of critical care CPGs with a focus on pharmacotherapy using the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. METHOD: A cross-sectional study of CPGs published from 2013 through August 2021 was conducted. Following establishment of interrater reliability, guidelines were independently evaluated by three reviewers to rate guidelines on criteria set forth by the AGREE II instrument. Domain scores and item scores were calculated using the AGREE II user manual, and results described with descriptive statistics. RESULTS: Out of 192 guidelines identified, 73 met inclusion criteria and were screened using the AGREE II instrument. Most guidelines were authored by a professional organization or government agency. Domain quality scores were calculated for each domain as recommended by the AGREE II instrument. Domain 4 (clarity of presentation) had the highest AGREE II domain score with a median score of 87.0% (interquartile range: 79.6%-92.6%). Domain 5 (applicability) received the lowest domain score with a mean score of 41.8 ± 21.1%. The majority of guidelines were recommended for use as published or with modifications, while only six guidelines (8.2%) were not recommended for use. CONCLUSIONS: The majority of critical care guidelines that include pharmacotherapy recommendations were recommended for use by study authors when the AGREE II instrument was applied. While guidelines generally scored highly in clarity of presentation, additional time and effort should focus on providing solutions to guideline implementation and inclusion of patient preferences.

The Combination of Tocilizumab and Methylprednisolone Along With Initial Lung Recruitment Strategy in Coronavirus Disease 2019 Patients Requiring Mechanical Ventilation: A Series of 21 Consecutive Cases.

OBJECTIVE: To describe the outcomes with use of a combination of tocilizumab and methylprednisolone administered around the time of endotracheal intubation in patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. DATA SOURCES: Retrospective chart review. STUDY SELECTION/DATA EXTRACTION: Twenty-one consecutive patients with confirmed coronavirus disease 2019-associated hypoxemic respiratory failure requiring mechanical ventilation. Initial ventilator parameters were positive end-expiratory pressure 14 cm H2o and target plateau pressure 29 cm H2o to maximize lung recruitment. Methylprednisolone (125 mg every 6hr for 24 hr with tapering to 60 mg every 12 hr) was administered shortly after patients were intubated (median 11 hr after intubation). DATA SYNTHESIS: No patient in the cohort died while hospitalized (mortality, 0%; 95% CI, 0%-18%) and 18 patients have been discharged from the acute care setting. Twenty of 21 patients (95%) have been liberated from mechanical ventilation after a median duration of 8 days (range, 4-30 d). Following 48 hours of methylprednisolone, the A-a o2 gradient decreased from 455 ± 103 to 228 ± 109 mm Hg (difference 227 ± 108 mm Hg; p < 0.01). CONCLUSIONS: Our positive experience with tocilizumab in combination with methylprednisolone started early after endotracheal intubation may be one avenue for reducing the morbidity and mortality seen with severe coronavirus disease 2019 and merits further exploration in clinical studies.

Steady-State Ceftazidime-Avibactam Serum Concentrations and Dosing Recommendations in a Critically Ill Patient Being Treated for Pseudomonas aeruginosa Pneumonia and Undergoing Continuous Venovenous Hemodiafiltration.

Ceftazidime-avibactam (CAZ-AVI) is a novel intravenous ß-lactam/ß-lactamase inhibitor combination used in the treatment of multidrug-resistant (MDR) gram-negative infections. Although renal dosing recommendations exist for the medication, limited data are available for dosing in patients receiving continuous renal replacement therapy. In this report, we describe a case in which CAZ-AVI 2.5 g was administered as a 2-hour infusion every 8 hours to a 50-year-old critically ill patient with MDR Pseudomonas aeruginosa (CAZ-AVI minimum inhibitory concentration [MIC] 8 µg/ml) pneumonia who was also receiving continuous venovenous hemodiafiltration (CVVHDF). Total serum concentrations of both ceftazidime and avibactam were measured at ~0.5, 2, 4, and 6 hours after completion of the 2-hour infusion of the 11th dose of CAZ-AVI. Ceftazidime pharmacokinetic parameters were as follows: maximum serum concentration (Cmax ) 152.39 µg/ml, half-life 5.17 hours, volume of distribution at steady state (Vdss ) 11.51 L, clearance 1.54 L/hour, and area under the concentration-time curve (AUC) 1295.38 hour•µg/ml. This regimen achieved free ceftazidime serum concentrations more than 4 times the MIC for 100% of the dosing interval. Avibactam pharmacokinetic parameters were as follows: Cmax 35.83 µg/ml, half-life 5.92 hours, Vdss 12.44 L, clearance 1.45 L/hour, and AUC 343.44 hour•µg/ml, which achieved free avibactam concentrations above 1 µg/ml for 100% of the dosing interval. Higher CAZ-AVI dosing is critical in the treatment of pneumonia due to limited ceftazidime penetration into epithelial lining fluid; however, epithelial lining fluid drug concentrations were not collected or measured. Based on this case report and the available evidence, a dose of CAZ-AVI 2.5 g infused over 2 hours every 8 hours appears to be appropriate for critically ill patients who are being treated for pneumonia and are receiving CVVHDF.

Managing Nonoperable Intracranial Bleeding Associated With Apixaban: A Series of 2 Cases.

OBJECTIVE: To report 2 cases of nonoperable intracranial bleeding associated with apixaban managed by 3-factor prothrombin complex concentrate (PCC3). CASE SUMMARIES: Case 1 presented with a 1.3-cm left parieto-occipital hemorrhage and a thin subdural hematoma (SDH) on the left tentorium of the brain about 6 hours after his last dose of apixaban. Case 2 presented with a 4-mm left parafalcine SDH with time of most recent apixaban dose unknown. The patients received 24.9 to 25.5 U/kg of PCC3 with none to 1 U fresh frozen plasma (FFP) and demonstrated minimal or no progression in lesions measured by repeat computed tomography (CT) after treatment. One patient was discharged to a skilled nursing facility after 8 days; the other patient was discharged to home after 18 days. DISCUSSION: Apixaban has no specific antidote. Current bleeding management strategies are based on expert opinion. The risks and benefits for differing strategies are unclear, and little clinical experience for managing apixaban-associated intracranial bleeding has been reported to date. These cases describe the clinical use of PCC3 to manage parieto-occipital and subdural hemorrhage associated with apixaban in events not requiring surgical intervention. CONCLUSION: In these 2 cases, 25 U/kg PCC3, with none to one unit FFP, ceased apixaban-associated intracranial bleeding without apparent thrombogenic complications.

Early Versus Delayed Initiation of Pharmacological Venous Thromboembolism Prophylaxis After an Intracranial Hemorrhage.

BACKGROUND: Intracranial hemorrhage (ICH) accounts for up to 20% of all strokes with and carries an approximate 50% 30-day mortality. The risk of venous thromboembolism (VTE) is markedly higher in patients with ICH compared with ischemic strokes, but the optimal time to initiate pharmacological prophylaxis is ill-defined. DESIGN: Retrospective analysis. SETTING: University-affiliated, tertiary care center. PATIENTS: Patients admitted for a nontraumatic ICH who received pharmacological VTE prophylaxis during their first 30 hospital days. RESULTS: Of the 793 patients evaluated, 400 were included [142 (35.5%) early]. Rebleeding event rates were similar for early versus late [8 (5.6%) vs. 13 (5.0%), P=0.80] and rates of hospital-acquired VTEs were not statistically different [1 (0.7%) vs. 8 (3.1%), P=0.17]. The median time from admission to the first dose of pharmacological prophylaxis was similar in patients who experienced rebleeding versus those that did not [74 h (range, 38 to 110.5 h) vs. 63 h (range, 45 to 90.5 h), P=0.69]. There was a longer median time from admission to the first dose of pharmacological prophylaxis in patients who developed a VTE during the initial hospitalization versus those who did not [108 h (range, 73.3 to 187 h) vs. 63 h (range, 44.5 to 90 h), P=0.005]. CONCLUSIONS: Initiation of early pharmacological prophylaxis in ICH patients did not appear to increase the risk of rebleeding nor decrease the risk of VTE. Among those patients who did develop VTE during hospitalization, there was a longer median time from admission to the first dose of pharmacological prophylaxis.

Prophylactic Acid-Suppressive Therapy in Hospitalized Adults: Indications, Benefits, and Infectious Complications.

Acid-suppressive therapy for prophylaxis of stress ulcer bleeding is commonly prescribed for hospitalized patients. Although its use in select, at-risk patients may reduce clinically significant gastrointestinal bleeding, the alteration in gastric pH and composition may place these patients at a higher risk of infection. Although any pharmacologic alteration of the gastric pH and composition is associated with an increased risk of infection, the risk appears to be highest with proton pump inhibitors, perhaps owing to the potency of this class of drugs in increasing the gastric pH. With the increased risk of infection, universal provision of pharmacologic acid suppression to all hospitalized patients, even all critically ill patients, is inappropriate and should be confined to patients meeting specific criteria. Nurses providing care in critical care areas may be instrumental in screening for appropriate use of acid-suppressive therapy and ensuring the drugs are discontinued upon transfer out of intensive care or when risk factors are no longer present.

Impact of total body weight on 30-day mortality in patients with gram-negative bacteremia.

BACKGROUND: The impact of total body weight (TBW) on 30-day mortality associated with gram-negative bacteremia has not been previously evaluated. METHODS: The cohort included 323 patients >/ = 18 years old with gram-negative bacteremia (1/1/2008-8/31/2011) who received >/ = 48 hours of antibiotics. We compared 30-day mortality of TBW <70 kg vs. >/ = 70 kg with a multivariable stepwise logistic regression adjusting for age >/ = 70 years, cancer diagnosis, and Pitt bacteremia score of >/ = 4. RESULTS: The cohort was 57% TBW >/ = 70 kg and 43% TBW <70 kg. TBW >/ = 70 kg patients had lower 30-day mortality (11.0% vs. 16.3%), which was significant in the multivariable analysis (OR 0.45, 95% CI 0.21-0.97). Cancer and Pitt bacteremia score >/ = 4 were also independently associated with 30-day mortality. TBW was no longer significant when TBW <50 kg patients were excluded. CONCLUSION: TBW >/ = 70 kg was associated with an improved 30-day mortality; however, the high mortality rates for patients with a TBW < 50 kg is responsible for this association.