Propofol-Associated Hypertriglyceridemia in Adults With Acute Respiratory Distress Syndrome on Extracorporeal Membrane Oxygenation.

The incidence and risk factors for propofol-associated hypertriglyceridemia (HTG) in patients receiving extracorporeal membrane oxygenation (ECMO) have not been evaluated. The purpose of this study was to determine the incidence and risk factors for propofol-associated HTG in patients with acute respiratory distress syndrome (ARDS) on ECMO. This retrospective, cohort study included 167 adults admitted to a medical intensive care unit (ICU) from July 1, 2013 to September 1, 2021, who received 24 hours of concurrent propofol and ECMO therapy. The primary outcome was the incidence of propofol-associated HTG. Secondary outcomes included HTG risk factors, time to development and resolution of HTG, and incidence of pancreatitis. HTG occurred in 58 (34.7%) patients. Patients with HTG had longer durations of ECMO (19 vs. 13 days, p < 0.001), longer ICU length of stay (26.5 vs. 23 days, p = 0.002), and higher in-hospital mortality (51.7 vs. 34.9%, p = 0.047). Baseline sequential organ failure assessment score was associated with an increased risk of developing HTG (hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 1.09-1.30; p < 0.001). Propofol-associated HTG occurred in one-third of patients receiving ECMO for ARDS. Higher baseline illness severity and ECMO duration were associated with an increased risk of propofol-associated HTG.

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.

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.

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.

Evidence of burnout in critical care pharmacists.

PURPOSE: Studies of critical care physicians and nursing personnel indicate a potentially high rate of burnout. To date there is a paucity of data in critical care pharmacists assessing burnout in this group. The purpose of this study was to assess the incidence of risk of burnout in critical care pharmacists. METHODS: Critical care pharmacists were solicited via email to complete an anonymous, electronic questionnaire regarding burnout. Subject demographic and employment characteristics were collected along with the validated, 22-item Maslach Burnout Inventory Health Services Survey in the study cohort. Burnout was assessed from 3 aspects, emotional exhaustion, depersonalization, and lack of personal accomplishment. High degree of burnout was defined as a score >27 in emotional exhaustion, or score >10 in depersonalization, or score <33 in personal achievement. Risk factors of burnout were evaluated using descriptive statistics and logistic regression. RESULTS: Out of 3,140 critical care pharmacists, 193 (6.1%) completed surveys. The mean scores were 25.3, 7.5, and 36.7 for emotional exhaustion, depersonalization, and reduced personal achievement, respectively. Overall, 123 pharmacists (64%) reported at least one syndrome of burnout, and 28 pharmacists (14.5%) reported burnout in all 3 scales. No single risk factor was identified to be associated with the risk of burnout. CONCLUSION: Risk of burnout is high in critical care pharmacists, at 64%, and is comparable to the risk in other critical care practitioner groups. This emphasizes the importance of continuing to evaluate risk factors for burnout and providing resources for burnout prevention to high-risk practitioners.

Evaluation of Rescue Thrombolysis in Cardiac Arrest Secondary to Suspected or Confirmed Pulmonary Embolism.

BACKGROUND: Pulmonary embolism (PE) is the associated cause of unexplained cardiac arrest in 5% to 13% of patients. Although thrombolytic agents have been studied, patient outcomes during cardiac arrest are lacking. OBJECTIVE: The purpose of this study was to describe outcomes of patients who received thrombolytic therapy during cardiac arrest for suspected or confirmed PE. METHODS: This retrospective review included adults who received alteplase or tenecteplase during cardiac arrest for suspected or confirmed PE. The primary end point was incidence of survival to hospital discharge, whereas secondary end points included a description of dosing strategies of thrombolytic therapy, the incidence of return of spontaneous circulation (ROSC), the occurrence of minor or major bleeding, and intensive care unit and hospital lengths of stay. RESULTS: Of the 22 patients included in the study, 3 patients (13.6%) survived to hospital discharge, and ROSC was obtained in 11 patients (50%). Three patients had confirmed PE prior to cardiac arrest, with the remaining 19 patients having a documented suspicion for PE. The most frequent dosing strategy was alteplase 100 mg given via intravenous push (13 of 22 patients; 59%). One minor and no major bleeding events occurred. Conclusion and Relevance: Medical advances in PE management continue to evolve; yet the role of thrombolytic therapy in PE-related cardiac arrest remains unclear, with low overall rates of survival. These findings add to the relatively small body of evidence and highlight that optimal dosing remains unknown in this setting.

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.

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.

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.

Association Between Deep Sedation from Continuous Intravenous Sedatives and Extubation Failures in Mechanically Ventilated Patients in the Pediatric Intensive Care Unit.

OBJECTIVE: The primary objective of this study was to determine whether an association exists between deep sedation from continuous infusion sedatives and extubation failures in mechanically ventilated children. Secondary outcomes evaluated risk factors associated with deep sedation. METHODS: This was a retrospective cohort study conducted between January 1, 2009, and October 31, 2012, in the pediatric intensive care unit (PICU) at Duke Children's Hospital. Patients were included in the study if they had been admitted to the PICU, had been mechanically ventilated for ≥48 hours, and had received at least one continuous infusion benzodiazepine and/or opioid infusion for ≥24 hours. Patients were separated into 2 groups: those deeply sedated and those not deeply sedated. Deep sedation was defined as having at least one documented State Behavioral Scale (SBS) of -3 or -2 within 72 hours prior to planned extubation. RESULTS: A total of 108 patients were included in the analysis. Both groups were well matched with regard to baseline characteristics. For the primary outcome, there was no difference in extubation failures in those who were deeply sedated compared to those not deeply sedated (14 patients [22.6%] versus 7 patients [15.2%], respectively; p = 0.33). After adjusting for potential risk factors, patients with a higher weight percentile for age (odds ratio [OR] 1.02; 95% confidence interval [CI] 1.00-1.03), lower Glasgow Coma Score (GCS) score prior to intubation (OR 0.85; 95% CI 0.74-0.97), and larger maximum benzodiazepine dose (OR 1.93; 95% CI 1.01-3.71) were associated with greater odds of deep sedation. A higher GCS prior to intubation was significantly associated with increased odds of extubation failure (OR 1.19; 95% CI 1.02-1.39). CONCLUSIONS: While there was no statistically significant difference in extubation failures between the 2 groups included in this study, considering the severe consequences of extubation failure, the numerical difference reported may be clinically important.