Characterization of an andexanet alfa administration protocol guided by drug-specific quantitative anti-Xa assays.

Following FDA approval in 2018, consensus guidelines recommend andexanet alfa as first-line therapy for the management of life-threatening or uncontrollable bleeding in patients taking oral factor Xa (FXa) inhibitors. Dosing is based on the specific FXa inhibitor and dose, and the time elapsed since the patient's last administration of the medication. Additionally, at our institution, anti-FXa screens and drug-specific assays are obtained to guide subsequent dosing based on institution protocol. The objective of this study was to evaluate andexanet alfa utilization based on anti-Xa and FXa-inhibitor-specific assays and assess associated outcomes. This was a retrospective, single-center study aimed to describe the use of anti-FXa and specific direct oral anticoagulant assays to guide the utilization and administration of andexanet alfa. Secondary endpoints evaluated included thrombotic events during index hospitalization, hospital length of stay, hospital mortality, and discharge disposition. Overall, most patients were prescribed apixaban for atrial fibrillation and received andexanet alfa for reversal of intracranial hemorrhage in the emergency department. In general, DOAC-specific assays were concordant with last known times; however, there appears to be minimal correlation with DOAC-specific assay levels and survival. There were 9 thrombotic events (8.7%) in 8 patients. In this cohort, collection of an anti-FXa assay screen was a practical strategy to guide reversal with andexanet alfa; however, the addition of DOAC-specific assay levels may not enhance clinical utility.

Simulation-Based Training to Improve Clinical Pharmacist Self-Efficacy in the Management of a Rapidly Decompensating Patient.

Background: The optimal training method to prepare pharmacists as an integral rapid response team or cardiopulmonary arrest responders is poorly described. This study assessed the utility of simulation-based training (SBT) as a training technique for clinical pharmacists. Objective: This study aimed to determine if attending SBT is associated with an improvement in self-efficacy. Methods: This single-center, prospective, interventional cohort study offered three simulations to clinical pharmacists over the course of seven months at a 957-bed quaternary care academic medical center. Pharmacists who participated in at least one simulation were categorized in the intervention group and were compared to pharmacists who did not attend a simulation. All participants were asked to complete a 19-question self-efficacy survey in the form of a 100-point scale, a 15-question multiple-choice knowledge assessment, and a perception survey in the form of 4-point Likert scale administered at baseline and following the conclusion of the SBT. Results: Forty-four clinical pharmacists participated; 20 in the intervention group and 24 in the control group. Median change in self-efficacy score improved significantly in the intervention group compared to the control group (14.3 vs 2.3, P = .009). Median change in perception score improved significantly (2 vs 0, P = .046). Knowledge score did not change significantly from baseline. Conclusion: Simulation-based training improved clinical pharmacist self-efficacy and perceptions in the care of rapidly decompensating patients. These findings support SBT as a viable modality of training clinical pharmacists for the management of rapidly decompensating patients.

Incidence and associated risk factors for systemic drug levels with inhaled aminoglycoside therapy.

OBJECTIVES: To characterize the incidence of and risk factors for a detectable drug level (DDL) in patients that received inhaled aminoglycoside therapy. METHODS: This retrospective, single-centre study included adult patients who received at least one dose of an inhaled aminoglycoside with a drug level during inpatient hospitalization. Patients were excluded if they received an aminoglycoside intravenously within 7 days or if the drug level was not drawn within 4 h of the next dose. A repeated measures logistic regression model evaluated the association between potential risk factors and a DDL. RESULTS: Among 286 drug levels, 88 (30.8%) drug levels were detectable. In multivariable analysis, cystic fibrosis (CF) (OR: 3.03; 95% CI: 1.10-8.35), chronic kidney disease (CKD) (OR: 4.25; 95% CI: 1.84-9.83), lung transplant recipient (OR: 3.08; 95% CI: 1.09-8.73), mechanical ventilation (OR: 2.99; 95% CI: 1.25-7.15) and tobramycin (OR: 5.26; 95% CI: 2.35-11.78) were associated with higher odds of a DDL. Among those with a DDL, inhaled aminoglycoside type and drug level concentration were not associated with acute kidney injury (P = 0.161). CONCLUSIONS: Among 286 drug levels identified among inpatients receiving inhaled aminoglycoside therapy, 88 (30.8%) unique drug levels were detectable. Based on the results of this study, periodic trough concentrations should be considered for patients receiving inhaled aminoglycoside therapy with CF, CKD, lung transplantation, mechanical ventilation or tobramycin.

Evaluation of Levetiracetam Dosing Strategies for Seizure Prophylaxis Following Traumatic Brain Injury.

BACKGROUND: Although levetiracetam has been increasingly used as an alternative to phenytoin for early posttraumatic seizure prophylaxis following traumatic brain injury (TBI), an optimal dosing strategy has not been elucidated. The objective of this study is to determine whether different dosing strategies of levetiracetam are associated with the incidence of early posttraumatic seizures when used as prophylaxis following TBI. METHODS: This retrospective single-center cohort study included admitted patients ≥ 18 years of age with a diagnosis of TBI and receiving levetiracetam for early posttraumatic seizure prophylaxis between July 1, 2013, and September 1, 2019. The primary outcome of this study was to evaluate three different dosing strategies of levetiracetam (≤ 1000 mg/day, 1500 mg/day, and ≥ 2000 mg/day) and associated rates of early posttraumatic seizures. Secondary outcomes were to summarize absolute total daily maintenance doses of levetiracetam among patients who experienced early posttraumatic seizures compared with those who did not, to determine the impact of three different dosing strategies on hospital length of stay and in-hospital mortality, and to assess patient-specific variables on the occurrence of posttraumatic seizures. Overlap propensity score weighting was used to address the potential for confounding. RESULTS: Of the 1287 patients who received levetiracetam for early posttraumatic seizure prophylaxis during the study time frame, 866 patients met eligibility criteria and were included in the study cohort (289 patients in the ≤ 1000 mg/day group, 137 patients in the 1500 mg/day group, and 440 patients in the ≥ 2000 mg/day group). After weighting, the cumulative incidence of early posttraumatic seizure was 2.9% in the ≤ 1000 mg/day group, 8.8% in the 1500 mg/day group, and 9% in the ≥ 2000 mg/day group. The 1500 mg/day and ≥ 2000 mg/day levetiracetam groups had a 209% and 216% increase in the subdistribution hazard of early posttraumatic seizures compared with the ≤ 1000 mg/day levetiracetam group, respectively, but these differences were not statistically significant. CONCLUSIONS: In conclusion, the results of this study demonstrate no statistically significant difference in the cumulative incidence of early posttraumatic seizures within 7 days of TBI between three different levetiracetam dosing strategies. After weighting, the ≤ 1000 mg/day levetiracetam group had the lowest rates of early posttraumatic seizures, death without seizure, and in-hospital mortality.

Effect of Initial Anticoagulation Targets on Bleeding and Thrombotic Complications for Patients With Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the effect of anticoagulation targets and intensity on bleeding events, thrombotic events, and transfusion requirements in patients with acute respiratory distress syndrome (ARDS) receiving venovenous extracorporeal membrane oxygenation (ECMO) and continuous-infusion heparin. DESIGN: A retrospective cohort study. SETTING: At a single-center, large academic medical center. PARTICIPANTS: One hundred thirty-six critically ill patients. INTERVENTIONS: The following three therapeutic targets were implemented over time and evaluated: (1) no protocol (September 2013-August 2016): no standardized anticoagulation protocol or transfusion thresholds; (2) <50 seconds (September 2016-January 2018): standardized activated partial thromboplastin time (aPTT) goal of <50 seconds, maximum heparin infusion rate of 1,200 units/h, transfusion threshold of hemoglobin (Hgb) <8 g/dL; and (3) 40-to-50 seconds (February 2018-December 2019): aPTT goal of 40-to-50 sec, no maximum heparin infusion rate, transfusion threshold of Hgb <7 g/dL. MEASUREMENTS AND MAIN RESULTS: Continuous variables were compared using the Kruskal-Wallis test, and categorical variables were compared using Fisher exact tests. The primary endpoint, an incidence of at least 1 bleeding event, was highest in the no-protocol group though not statistically different among groups (39.3% v 26.7% v 34%, p = 0.5). Thrombotic complications were similar. The median units of packed red blood cells transfused were highest in the no-protocol group (3 v 2 v 0.5, p < 0.001). CONCLUSION: Anticoagulation protocols standardizing aPTT goals to <50 or 40-to-50 seconds may be a reasonable strategy for patients receiving venovenous ECMO for ARDS. More restrictive hemoglobin transfusion thresholds, in combination with lower aPTT targets, may be associated with a reduction in transfusion requirements.

The Predictive Value of the 4Ts and HEP Score at Recommended Cutoffs in Patients With Mechanical Circulatory Support Devices.

OBJECTIVES: Despite the increasing utilization of mechanical circulatory support (MCS) devices, the 4Ts and heparin-induced thrombocytopenia (HIT) Expert Probability (HEP) scores have not been validated in patients with suspected HIT requiring MCS. DESIGN: A retrospective cohort study. SETTING: At a tertiary university hospital. PARTICIPANTS: Adults with suspected HIT requiring any MCS. INTERVENTIONS: A diagnostic investigation of HIT. MEASUREMENTS AND MAIN RESULTS: Of the 299 patients included, there were 374 diagnostic investigations of HIT, of which 32 (8.6%) were HIT-probable (heparin PF4 immunoassay optical density ≥1 or positive serotonin release assay). The 4Ts score ≥4 demonstrated a pretest sensitivity of 0.56 (95% confidence interval [CI]: 0.39-0.72) and specificity of 0.8 (95% CI: 0.75-0.83). The HEP score ≥3 demonstrated a pretest sensitivity of 0.31 (95% CI: 0.18-0.49) and specificity of 0.83 (95% CI: 0.79-0.87). The area under the receiver operating characteristic curve for the 4Ts and HEP scores were 0.68 (95% CI: 0.63-0.73) and 0.63 (95% CI: 0.59-0.68), respectively, and were not statistically different (p = 0.21). In patients with an intra-aortic balloon pump, neither the 4Ts nor HEP score had discriminatory ability to differentiate probable HIT. The HEP score had no discriminatory ability in patients with concomitant MCS devices. CONCLUSIONS: The 4Ts and HEP scores have a modest predictive performance for probable HIT in patients requiring MCS devices. A low 4Ts or HEP score does not reliably rule out HIT in patients requiring MCS, and clinical suspicion for HIT should be investigated, utilizing laboratory tests in this population.

Comparison of intermittent versus continuous infusion antihypertensives in acute ischemic stroke.

BACKGROUND: The optimal approach to blood pressure (BP) management in acute ischemic stroke remains unclear. The purpose of this study was to determine if an intermittent (labetalol or hydralazine) or continuous infusion (nicardipine or clevidipine) antihypertensive strategy facilitated timelier alteplase administration. METHODS: Patients ≥18 years who presented to the emergency department (ED) between September 1, 2013 and August 31, 2020, received alteplase for acute ischemic stroke, and required BP management with an intravenous antihypertensive were included in this multicenter, retrospective cohort study. Exclusion criteria were initial administration of a non-study antihypertensive, initial study antihypertensive administration >2 hours prior to or any time following alteplase, or receipt of both an intermittent and continuous infusion antihypertensive prior to alteplase. The primary endpoint was the time from ED presentation to alteplase administration. RESULTS: During the study period, 122 patients received an intermittent antihypertensive and 57 patients received a continuous infusion antihypertensive. The median door-to-needle time was 53 minutes for patients who received an intermittent antihypertensive compared to 57 minutes for those who received a continuous infusion antihypertensive (p=0.17). Secondarily, the proportion of patients who achieved the BP target <185/110 mmHg within 15 minutes of initial antihypertensive administration and the incidence of adverse events were similar between treatment groups. In cost analysis, intermittent antihypertensives were less expensive than continuous infusion antihypertensives ($2.20 vs. $71.40). CONCLUSIONS: Among patients with acute ischemic stroke and uncontrolled BP, the initial use of an intermittent or continuous infusion antihypertensive did not significantly impact the time to alteplase administration.

Hydroxocobalamin or Methylene Blue for Vasoplegic Syndrome in Adult Cardiothoracic Surgery.

OBJECTIVE: To compare hydroxocobalamin and methylene blue for the treatment of vasopressor-refractory vasoplegic syndrome (VS) after adult cardiac surgery with cardiopulmonary bypass (CPB). DESIGN: A retrospective, propensity-matched, cohort study was performed. The primary endpoints were the percentage change in vasopressor use at 30, 60, and 120 minutes, characterized as both norepinephrine equivalents and vasoactive inotropic score. Eligible patients who received methylene blue were matched 3:1 with patients who received hydroxocobalamin based on sequential organ failure assessment score, preoperative mechanical circulatory support, CPB duration, and use of pre-CPB vasopressors, angiotensin-converting enzyme inhibitors, or beta-blockers. SETTING: A quaternary care academic medical center. PARTICIPANTS: Adult patients who underwent cardiac surgery with CPB from July 2013 to June 2019. INTERVENTIONS: Patients were included who received either hydroxocobalamin (5,000 mg) or methylene blue (median 1.2 mg/kg) for VS in the operating room during the index surgery or in the intensive care unit up to 24 hours after CPB separation. MEASUREMENTS AND MAIN RESULTS: Of the 142 included patients, 120 received methylene blue and 22 received hydroxocobalamin. After matching, 66 patients in the methylene blue group were included in the analysis. Baseline demographics, surgical characteristics, and vasoactive medications were similar between groups. There were no significant between-group differences in percentage change in norepinephrine equivalents or vasoactive inotropic score at each timepoint. CONCLUSIONS: In adult patients undergoing cardiothoracic surgery using CPB with VS, the ability to reduce vasopressor use was similar with hydroxocobalamin compared with methylene blue.

Impact of a Real-Time, Pharmacist-Led, Intensive Care Unit-Based Feedback Intervention on Analgesia and Sedation Quality Among Mechanically Ventilated Patients.

BACKGROUND: Consensus guidelines for pain, agitation, and delirium (PAD) in mechanically ventilated patients recommend maintaining a light level of sedation. LOCAL PROBLEM: Consistent attainment of target PAD assessments in mechanically ventilated ICU patients is often challenging. METHODS: This is a single-center, prospective study. INTERVENTIONS: In the intervention group, a pharmacist provided weekly feedback to nurses on their success in achieving target PAD assessments compared with a historical cohort without feedback. RESULTS: Overall, 478 patients and 205 nurses were included. The odds of having weekly Richmond Agitation-Sedation Scale (RASS) score, pain score goals, and Confusion Assessment Method for the ICU (CAM-ICU) negative assessments at goal between the intervention and control groups fluctuated over time without a discernible trend. CONCLUSION: The provision of weekly feedback to nurses on PAD nursing assessments by a pharmacist did not impact the achievement of PAD goals among critically ill mechanically ventilated patients.

Characterization of Isavuconazole serum concentrations after enteral feeding tube administration in a hospitalized cohort: A case series.

WHAT IS KNOWN AND OBJECTIVE: Invasive fungal infections often occur in patients with comorbidities that complicate oral administration. Serum concentrations of isavuconazole were characterized after enteral tube administration. CASE DESCRIPTION: Thirteen of 14 isavuconazole concentrations were >1 mg/dl (median 1.6 mg/dl) among those receiving enteral tube administration, which was comparable to intravenous (median 1.9 mg/dl). Higher concentrations were observed during oral administration (median 3 mg/dl). WHAT IS NEW AND CONCLUSION: Administration of isavuconazole via tube resulted in concentrations comparable to FDA-approved routes of administration. This route may be feasible and appropriate for select patients.

VanA rectal swab screening as a predictor of subsequent vancomycin-resistant enterococcal bloodstream infection in critically ill adults.

OBJECTIVE: To evaluate whether vanA rectal screening for vancomycin-resistant Enterococcus (VRE) predicts vancomycin resistance for patients with enterococcal bloodstream infection (BSI). DESIGN: A retrospective cohort study. SETTING: Large academic medical center. METHODS: The predictive performance of a vanA rectal swab was evaluated in 161 critically ill adults with an enterococcal BSI from January 1, 2007, to September 1, 2014, and who had a vanA rectal swab screening obtained within 14 days prior to blood culture. RESULTS: Of the patients meeting inclusion criteria, 83 (51.6%) were vanA swab positive. Rectal-swab-positive patients were more likely to be younger, to be immunocompromised, to have an indwelling central vascular catheter, and to have a history of MDR bacteria. The vanA rectal swab had sensitivity and negative predictive values of 83.6% and 85.9%, respectively, and specificity and positive predictive values of 71.3% and 67.5%, respectively, for predicting a vancomycin-resistant enterococcal BSI in critically ill adults. CONCLUSIONS: VanA rectal swabs may be useful for antimicrobial stewardship at institutions with VRE screening already in place for infection control purposes. A higher PPV would be warranted to implement a universal vanA screen on all ICU patients.

Effectiveness of Quetiapine as a Sedative Adjunct in Mechanically Ventilated Adults Without Delirium.

BACKGROUND: Quetiapine is an atypical antipsychotic that is commonly used in the Intensive Care Unit (ICU). The utility of quetiapine as a sedative adjunct has not yet been evaluated, but has been described previously in studies evaluating quetiapine for delirium or delirium prophylaxis. OBJECTIVE: To determine if adjunctive use of quetiapine reduces sedative dosage requirements among mechanically ventilated adults without delirium. METHODS: This retrospective intrapatient comparator study included all mechanically ventilated adults admitted to a medical ICU who received quetiapine between July 1, 2013, and July 1, 2018. The primary outcome was the change in sedative dosage requirements over 24 hours following quetiapine initiation. Secondary outcomes included change in sedative dosage requirements 48 hours postquetiapine initiation, opioid dosage requirements 24 hours postquetiapine initiation, percent time at goal for both pain and sedation scores, depth of sedation, and QTc. RESULTS: A total of 57 patients were included in the study cohort. There was no significant difference in 24-hour cumulative doses of propofol (P = 0.10), dexmedetomidine (P = 0.14), or benzodiazepines (P = 0.14). During the 48-hour treatment period, there was a significant increase in dexmedetomidine requirements (P = 0.03). There were no differences in 24-hour opioid dosage requirements, percent time at goal pain or sedation scores, depth of sedation, or QTc following quetiapine initiation. CONCLUSION AND RELEVANCE: Adjunctive use of quetiapine was not associated with a significant reduction in sedative dosage requirements 24 or 48 hours following initiation among mechanically ventilated adults without delirium.

Boarding of critically Ill patients in the emergency department.

OBJECTIVES: Emergency department boarding is the practice of caring for admitted patients in the emergency department after hospital admission, and boarding has been a growing problem in the United States. Boarding of the critically ill has achieved specific attention because of its association with poor clinical outcomes. Accordingly, the Society of Critical Care Medicine and the American College of Emergency Physicians convened a Task Force to understand the implications of emergency department boarding of the critically ill. The objective of this article is to review the U.S. literature on (1) the frequency of emergency department boarding among the critically ill, (2) the outcomes associated with critical care patient boarding, and (3) local strategies developed to mitigate the impact of emergency department critical care boarding on patient outcomes. DATA SOURCES AND STUDY SELECTION: Review article. DATA EXTRACTION AND DATA SYNTHESIS: Emergency department-based boarding of the critically ill patient is common, but no nationally representative frequency estimates has been reported. Boarding literature is limited by variation in the definitions used for boarding and variation in the facilities studied (boarding ranges from 2% to 88% of ICU admissions). Prolonged boarding in the emergency department has been associated with longer duration of mechanical ventilation, longer ICU and hospital length of stay, and higher mortality. Health systems have developed multiple mitigation strategies to address emergency department boarding of critically ill patients, including emergency department-based interventions, hospital-based interventions, and emergency department-based resuscitation care units. CONCLUSIONS: Emergency department boarding of critically ill patients was common and was associated with worse clinical outcomes. Health systems have generated a number of strategies to mitigate these effects. A definition for emergency department boarding is proposed. Future work should establish formal criteria for analysis and benchmarking of emergency department-based boarding overall, with subsequent efforts focused on developing and reporting innovative strategies that improve clinical outcomes of critically ill patients boarded in the emergency department.

Boarding of Critically Ill Patients in the Emergency Department.

OBJECTIVES: Emergency department boarding is the practice of caring for admitted patients in the emergency department after hospital admission, and boarding has been a growing problem in the United States. Boarding of the critically ill has achieved specific attention because of its association with poor clinical outcomes. Accordingly, the Society of Critical Care Medicine and the American College of Emergency Physicians convened a Task Force to understand the implications of emergency department boarding of the critically ill. The objective of this article is to review the U.S. literature on (1) the frequency of emergency department boarding among the critically ill, (2) the outcomes associated with critical care patient boarding, and (3) local strategies developed to mitigate the impact of emergency department critical care boarding on patient outcomes. DATA SOURCES AND STUDY SELECTION: Review article. DATA EXTRACTION AND DATA SYNTHESIS: Emergency department-based boarding of the critically ill patient is common, but no nationally representative frequency estimates has been reported. Boarding literature is limited by variation in the definitions used for boarding and variation in the facilities studied (boarding ranges from 2% to 88% of ICU admissions). Prolonged boarding in the emergency department has been associated with longer duration of mechanical ventilation, longer ICU and hospital length of stay, and higher mortality. Health systems have developed multiple mitigation strategies to address emergency department boarding of critically ill patients, including emergency department-based interventions, hospital-based interventions, and emergency department-based resuscitation care units. CONCLUSIONS: Emergency department boarding of critically ill patients was common and was associated with worse clinical outcomes. Health systems have generated a number of strategies to mitigate these effects. A definition for emergency department boarding is proposed. Future work should establish formal criteria for analysis and benchmarking of emergency department-based boarding overall, with subsequent efforts focused on developing and reporting innovative strategies that improve clinical outcomes of critically ill patients boarded in the emergency department.

Medication Histories in Critically Ill Patients Completed by Pharmacy Personnel.

BACKGROUND: Although critically ill adults often have extended hospital lengths of stay and are at high risk of having medication-related adverse events, the value of medication histories in these patients remains underreported. OBJECTIVE: To assess the feasibility of performing medication histories in critically ill adults and to establish the frequency of and characterize identified discrepancies. METHODS: This prospective study included patients admitted to 4 intensive care units (ICUs) in a large academic medical center and was conducted in 2 phases. In phase 1, medication histories were conducted over a 5-week period by clinical pharmacists to assess feasibility. In phase 2, medication histories were conducted over a 3-week period by a pharmacy technician. Medication discrepancies, defined as any difference between the documented and pharmacy personnel-identified home medication list, were aggregated in both phases and adjudicated for severity. RESULTS: In phase 1, 127 medication histories were completed (42.3% of admitted patients). Impaired cognition was the most common barrier encountered; however, 76% of patients were able to have a history completed if an attempt was made. In phase 2, a medication history was completed for 176 patients (58.9% of admitted patients). In aggregate, 1155 discrepancies were identified, with 78.2% of patients having a discrepancy. The median number of discrepancies per patient was 3 (interquartile range = 1-5); 11 life-threatening, 101 serious, and 326 significant discrepancies were identified. Conclusion and Relevance: A pharmacy personnel-based medication history program in the ICU is feasible and assists in the discovery of medication discrepancies with the potential for patient harm.

Effectiveness of Vancomycin or Beta-Lactam Therapy in Ampicillin-Susceptible Enterococcus spp. Bloodstream Infections.

BACKGROUND: De-escalation to a beta-lactam improves outcomes for patients with a methicillin-susceptible Staphylococcus aureus bloodstream infection (BSI). Whether a similar strategy is appropriate for enterococcal species is less clear. OBJECTIVE: To determine whether definitive antibiotic selection affects outcomes for patients with an ampicillin-susceptible enterococcal BSI. METHODS: This retrospective cohort study included patients over 18 years of age receiving definitive therapy with vancomycin or a beta-lactam for one or more blood cultures positive for Enterococcus spp. isolates between 2007 and 2014. Survival differences were examined using a Kaplan-Meier curve with log-rank test. RESULTS: One-hundred eighty-six patients received definitive therapy with either vancomycin (n = 45, 24.2%) or a beta-lactam (n = 141, 75.8%). The primary outcome, 30-day all-cause mortality, was not different between groups (6.7% vs 7.1%; P = .992). A post hoc analysis of all-cause mortality 1 year after the index BSI was significantly higher in the vancomycin group (51% vs 33%; P = .032). In a Cox proportional hazards regression model, definitive vancomycin was associated with an increased risk of all-cause mortality at 1 year (hazard ratio [HR]: 2.39; 95% confidence interval [CI]: 1.41-4.04). CONCLUSION: For patients with an ampicillin-susceptible enterococcal BSI, definitive therapy with vancomycin or a beta-lactam was not independently associated with a difference in 30-day all-cause mortality. Whether definitive vancomycin is associated with poor long-term outcomes warrants further exploration.

A Pharmacy-Based Electronic Handoff Tool to Reduce Discharge Prescribing of Atypical Antipsychotics Initiated in the Intensive Care Unit: A Quality Improvement Initiative.

PURPOSE: To evaluate whether a pharmacist-initiated electronic handoff tool can reduce the overall, and potentially inappropriate, hospital discharge prescribing rate of atypical antipsychotics (AAP) initiated in AAP-naive critically ill adults. METHODS: This pre-post quality improvement study was initiated in 5 intensive care units (ICUs) at a large academic medical center. An electronic handoff tool (iVent) was utilized in the post-intervention period to enhance pharmacist communication at inpatient transitions of care. RESULTS: Of the 358 included patients, the proportion of hospital survivors with an AAP initiated in the ICU receiving a hospital discharge prescription was not different between the pre- and post-intervention period (28.6% vs 22.2%, P = .12). The proportion of ICU survivors with an AAP continued at the time of ICU transfer to the floor was reduced post-intervention (78.7% vs 66.7%, P = .012). Additionally, the overall proportion of a patient's hospitalization receiving an AAP was also reduced (50.4% vs 42.8%, P = .008). A multivariate logistic regression demonstrated thatutilization of the electronic handoff tool was not associated with a reduction in hospital discharge prescribing of an AAP (odds ratio [OR]: 0.97, 95% confidence interval [CI]: 0.57-1.65). CONCLUSIONS: A pharmacy-initiated electronic handoff tool may reduce the proportion of AAP-naive ICU survivors with an AAP continued at the time of ICU transfer. The handoff tool was not associated with a significant reduction in the discharge prescribing rates of AAPs for hospital survivors, but a clinically meaningful reduction was possibly achieved due to enhanced communication enabled by this tool.

Discharge prescribing of enteral opioids after initiation as a weaning strategy from continuous opioid infusions in the Intensive Care Unit.

OBJECTIVE: To evaluate the proportion of patients receiving a hospital discharge prescription for a scheduled enteral opioid following initiation as a weaning strategy from a continuous opioid infusion in the Intensive Care Unit (ICU). DESIGN: Retrospective, observational study. SETTING: Five adult ICUs at a large, quaternary care academic medical center. PATIENTS: Endotracheally intubated, opioid-naive adults receiving a continuous opioid infusion with a concomitant scheduled enteral opioid initiated. Exclusion criteria were receipt of fewer than two enteral opioid doses, documentation of a long-acting opioid as a home medication, the indication for the enteral opioid was not a weaning strategy, death during hospital admission or discharge to hospice. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The proportion of ICU and hospital survivors who received a discharge prescription for a scheduled enteral opioid, total duration of continuous opioid infusion, duration of continuous opioid infusion after initiation of an enteral opioid therapy, total duration of enteral therapy, ICU and hospital length of stay. RESULTS: Of 62 included patients, 19 patients (30.6 percent) received a new prescription for a scheduled enteral opioid at hospital discharge. The median duration of enteral opioid therapy was longer for patients who received a discharge prescription compared to those who did not (20.09 vs 8.89 days, p = 0.02), though the remaining endpoints were not different. CONCLUSIONS: Utilizing scheduled enteral opioids as a weaning strategy from continuous opioid infusions may place patients at risk of ICU-acquired physical dependence on opioids.

Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo-obstruction, or Refractory Constipation.

BACKGROUND: Neostigmine is traditionally administered intravenously for treatment of acute colonic pseudo-obstruction (ACPO), though use is associated with administration constraints and adverse effects. OBJECTIVE: To evaluate whether an alternative route of administration for neostigmine via subcutaneous (SQ) delivery is safe and effective in a broad cohort of medical and surgical patients. METHODS: This multicenter, retrospective observational study included adult patients administered SQ neostigmine for ileus, ACPO, or refractory constipation. Efficacy indicators were time to first bowel movement (BM) following initiation of the medication, total SQ neostigmine dose administered to produce a BM, and administration of a rescue intervention to produce a BM. Safety events evaluated were cardiac arrest, bradycardia, bronchospasm requiring intervention, nausea requiring intervention, or severe salivation, lacrimation, or diarrhea. RESULTS: A total of 182 patients were eligible for inclusion. The most commonly utilized dosing strategy of neostigmine was 0.25 mg SQ 4 times daily. The median time to first BM following initiation of SQ neostigmine was 29.19 hours (interquartile range = 12.18-56.84) with a median dose administered before first BM of 1.25 mg. Three patients (1.65%) experienced an adverse drug event leading to drug discontinuation, with 2 developing bradycardia that resolved with drug discontinuation alone. CONCLUSIONS: SQ neostigmine may be reasonable for management of ileus, ACPO, or refractory constipation, though use should be avoided in patients with new-onset heart block, a history of second-degree heart block, or following bowel resection with primary anastomosis. Despite the low incidence of adverse drug events observed, monitoring for bradycardia with telemetry may be considered.

Predictors of Vasopressin Responsiveness in Critically Ill Adults.

BACKGROUND: Vasopressin is commonly used as an adjunct vasopressor in shock. However, response to vasopressin varies among critically ill patients. OBJECTIVE: To identify patient-specific factors that are associated with vasopressin responsiveness in critically ill adults. METHODS: This retrospective, multicenter study included adult patients who were admitted to an intensive care unit (ICU) and received vasopressin for shock. Patients were excluded if they received vasopressin for less than 30 minutes, if vasopressin was initiated prior to ICU arrival, or if an additional vasopressor was initiated within 30 minutes of starting vasopressin. Responsiveness was defined as an increase in mean arterial pressure of ≥10 mm Hg or the ability to taper a concurrent catecholamine vasopressor. Patient-specific factors evaluated in a multivariate analysis included age, gender, ethnicity, body mass index, type of shock, serum pH, Sequential Organ Failure Assessment (SOFA) score, and use of stress-dose steroids. These variables were also evaluated in a subgroup analysis of patients with septic shock. RESULTS: Of 1619 patients screened, 400 patients were included, with 231 identified as vasopressin responsive and 169 as nonresponsive. Vasopressin used as an adjunct vasopressor, as opposed to first line, during shock was the only variable associated with vasopressin responsiveness (odds ratio [OR] = 1.71; 95% CI = 1.10 to 2.65). Among the subgroup of patients with septic shock, female patients had a higher odds of responding than male patients (OR = 2.10; 95% CI = 1.12 to 3.95). CONCLUSIONS: Vasopressin initiated as an adjunct vasopressor, as opposed to first-line therapy, was associated with response.