Purpose To demonstrate a novel method that utilizes retrospective data to develop statistically optimal dosing strategies for medications with sensitive therapeutic windows. We illustrate our approach on intravenous unfractionated heparin, a medication which typically considers only patient weight and is frequently misdosed. Methods We identified available clinical features which impact patient response to heparin and extracted 1,511 patients from the multi-parameter intelligent monitoring in intensive care II database which met our inclusion criteria. These were used to develop two multivariate logistic regressions, modeling suband supra-therapeutic activated partial thromboplastin time (aPTT) as a function of clinical features. We combined information from these models to estimate an initial heparin dose that would, on a per-patient basis, maximize the probability of a therapeutic aPTT within 4–8 h of the initial infusion. We tested our model’s ability to classifying therapeutic outcomes on a withheld dataset and compared performance to a weight-alone alternative using volume under surface (VUS) (a multiclass version of AUC). Results We observed statistically significant associations between suband supra-therapeutic aPTT, race, ICU type, gender, heparin dose, age and Sequential Organ Failure Assessment scores with mean validation AUC of 0.78 and 0.79 respectively. Our final model improved outcome classification over the weight-alone alternative, with VUS values of 0.48 vs. 0.42. Conclusions This work represents an important step in the secondary use of health data in developing models to optimize drug dosing. The next step would be evaluating whether this approach indeed achieves target aPTT more reliably than the current weight-based heparin dosing in a randomized controlled trial.

Objective: Intravenous (IV) olanzapine could be an alternative to first-generation antipsychotics for the management of agitation in intensive care unit (ICU) patients. We compared the effectiveness and safety of IV olanzapine to IV haloperidol for agitation management in adult patients in the ICU at a tertiary academic medical center. Methods: A retrospective cohort study was conducted. The primary outcome was the proportion of patients who achieved a Richmond Agitation Sedation Scale (RASS) score of < +1 within 4 hours of IV olanzapine or IV haloperidol administration. Secondary outcomes included the proportion of patients who required rescue medications for agitation within 4 hours of initial IV olanzapine or IV haloperidol administration, incidence of adverse events and ICU length of stay. Results: In the 192 patient analytic cohort, there was no difference in the proportion of patients who achieved a RASS score of < +1 within 4 hours of receiving IV olanzapine or IV haloperidol (49% vs. 42%, p = 0.31). Patients in the IV haloperidol group were more likely to receive rescue medications (28% vs 55%, p < 0.01). There was no difference in the incidence of respiratory events or hypotension between IV olanzapine and IV haloperidol. Patients in the IV olanzapine group experienced more bradycardia (11% vs. 3%, p = 0.04) and somnolence (9% vs. 1%, p = 0.02) compared to the IV haloperidol group. Patients in the IV olanzapine group had a longer median ICU length of stay (7.5 days vs. 5 days, p = 0.04). Conclusion: In this retrospective cohort study, there was no difference in the effectiveness of IV olanzapine compared to IV haloperidol for the management of agitation. IV olanzapine was associated with an increased incidence of bradycardia and somnolence.

The authors describe a case of unfractionated heparin (UFH) unresponsiveness in the operating room secondary to reversal of rivaroxaban with coagulation factor Xa (recombinant) inactivated-zhzo (andexanet alfa). A 70-year-old man with a known 4.5-to 5.0-cm abdominal aortic aneurysm and atrial fibrillation managed with rivaroxaban presented with severe right-sided flank pain radiating to the left side of his abdomen. Computed tomography-angiography on arrival demonstrated a left retroperitoneal hematoma and a suspected ruptured abdominal aortic aneurysm. He received andexanet alfa to reverse rivaroxaban prior to an emergent endovascular aneurysm repair. During surgery, he received a total of 14,000 units (167 units/kg) of UFH with minimal changes in activated clotting time (132-144 sec; baseline 135 sec [reference range 74-137 sec]). This case highlights the potential complications of using UFH anticoagulation following reversal of factor Xa inhibitors with andexanet alfa and underscores the importance of peri-procedural anticoagulation planning. For patients who require intra-operative anticoagulation, providers should consider anticoagulation reversal with prothrombin complex concentrate instead of andexanet alfa or administration of a parenteral direct thrombin inhibitor, such as argatroban or bivalirudin during the surgical procedure. KEY WORDS andexanet alfa, factor Xa reversal, direct oral anticoagulants, unfractionated heparin unresponsiveness, rivaroxaban, abdominal aortic aneurysm, endovascular repair, endovascular aneurysm repair.

Background: The ACC/AHA heart failure (HF) guidelines include a class IIb recommendation for intravenous (IV) iron replacement in patients with iron deficiency and New York Heart Association class II or III to improve functional status and quality of life. Several studies have addressed the use of IV iron formulations such as ferric carboxymaltose or iron sucrose in HF population; however, few studies focused on sodium ferric gluconate complex (SFGC). Objectives: To assess the safety and effectiveness of an IV SFGC administration protocol in patients hospitalized with HF. Methods: A retrospective cohort study was conducted. We included patients admitted to the HF service from September 2017 to March 2018. The primary outcome was the frequency of adverse reactions. The secondary outcome was the odds of HF readmissions between the 2 groups (IV SFGC vs. control). Results: Of the 123 patients, 70 received IV iron (SFGC group) and 53 did not receive IV iron (control group). Five (7%) patients of the 70 in the SFGC group experienced adverse events, which included hypotension (n = 2, 2.8%), fever (n = 2, 2.8%) and myalgia (n = 2, 2.8%). Nine (12.8%) and 18 (25.7%) were readmitted within 30 days and 6 months respectively. In the control arm, 5 (9.4%) and 14 (26.4%) were admitted within 30 days and 6 months respectively. The odds of HF readmission at 30 days [OR 1.4 (95% CI: 0.45, 4.5)] and at 6 months [OR 0.96 (95% CI: 0.43, 2.2)] were similar in those who did not receive IV iron compared to those who received IV iron. Conclusions: Sodium ferric gluconate complex given at an accelerated dosing schedule appears to provide a more efficient means to prescribe IV iron in the inpatient setting and is safe with a low frequency of hypotension, fevers, and myalgias.

Background Hope is negatively associated with parental psychosocial distress and psychological maladjustment as well as an important aspect of emotional well-being and coping for adults with cancer and their caregivers. Yet, little is known about hope experiences of parents of children with cancer. Objective The aim of this study was to comprehensively describe hope experiences in parents of children with cancer using a systematic mixed-studies review. Intervention/Methods Psych INFO, PubMed, Academic Search Premier, and CINAHL databases were used to retrieve articles published in English between January 2005 and October 2019. Using the systematic mixed-studies review convergent design, qualitative and quantitative data were collected and extracted followed by qualitative synthesis. Seventeen articles met the inclusion criteria. Exclusion criteria were systematic reviews, nonresearch articles, case reports, and abstracts. Results Hope is a fundamental source of strength and inner guidance for parents. Findings suggest that hope is negatively correlated with parental psychological distress symptoms and coping dysfunctions. Religiosity, spirituality, and adequate provider-parent communication may strengthen hope in parents. Conclusion Parental hope may help minimize psychological distress and maladjustment after a child’s cancer diagnosis. Open communication channels between providers and parents are critical in preserving hope. An understanding of religiosity, spirituality, optimism, and sociodemographic variables may inform parental psychosocial interventions. Implications for Practice Early identification of parents with psychological distress is critical as they may struggle more in the absence of hope. Targeted psychosocial interventions may help parents of children with cancer cope better. Ongoing assessments of spiritual needs may be important in sustaining hope.

Children with cancer experience multiple symptoms at end of life (EOL) that impair their health-related quality of life. Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, this integrative literature review comprehensively summarized symptom experiences of children with cancer at EOL. The Cumulative Index to Nursing and Allied Health Literature (CINAHL), PubMed, and Academic Premier were searched between January 2007 to September 2019 for articles published in English using the MeSH terms: symptom burden or distress AND children with cancer or pediatric cancer or cancer children or oncology and pediatrics AND EOL care or palliative care or death or dying or terminally ill. The inclusion criteria were the following: (a) study designs [randomized controlled trials, nonexperimental, secondary analysis (if aims were distinct from primary studies) and qualitative]; (b) participants <18 years old (died of cancer, had no realistic chance of cure, or had advanced cancer); and (c) focused on symptom experiences/burden at EOL. Exclusion criteria were nonresearch articles, systematic reviews, case studies, reports, and studies that focused on cancer survivors and/or those receiving curative therapies. Twenty-seven articles met inclusion criteria. The most prevalent symptoms—pain, fatigue, dyspnea, and loss of appetitewere associated with impairments in health-related quality of life. Children with brain tumors experienced higher symptom burden compared to those with hematologic/solid malignancies. Children who received cancer-directed therapies experienced disproportionate symptoms and were more likely to die in the intensive care unit compared with those who did not receive cancer-directed therapies. Most common location of death was home. This integrative review indicated that children with cancer were polysymptomatic at EOL. Strategies facilitating effective symptom management at EOL are needed.

While technological innovations are the invariable crux of speculation about the future of critical care, they cannot replace the clinician at the bedside. This article summarizes the work of the Society of Critical Care Medicine–appointed multiprofessional task for the Future of Critical Care. The Task Force notes that critical care practice will be transformed by novel technologies, integration of artificial intelligence decision support algorithms, and advances in seamless data operationalization across diverse healthcare systems and geographic regions and within federated datasets. Yet, new technologies will be relevant and meaningful only if they improve the very human endeavor of caring for someone who is critically ill.

Purpose: Catecholamines are first-line vasopressors for hemodynamic support in distributive shock but are associated with adverse effects, which may be mitigated with noncatecholamine vasopressors. Angiotensin II (ATII) is a noncatecholamine vasopressor recently approved for the management of distributive shock, but limited data support its clinical utility. The purpose of this study was to describe our institution’s usage of ATII including patient outcomes (eg, response to therapy, safety profile). Materials and Methods: Patients who received ATII at our institution were included. Patient demographics, degree of concordance with institutional ATII use guidelines, safety profile of ATII, and response to therapy (1 and 3 hours after ATII initiation) were collected. Results: A total of 16 patients received ATII for distributive shock. The median Sequential Organ Failure Assessment score at the time of ATII initiation was 16.5 (interquartile range: 15.8-20.0). Fourteen (87.5%) patients met institutional guidelines for ATII use; 10 (62.5%) and 8 (50.0%) patients met our definition for response at 1 and 3 hours, respectively. No patients developed thrombotic or infectious complications after receiving ATII. Conclusions: In this cohort, ATII appears to be well tolerated in patients with a high predicted mortality. Future studies evaluating the clinical efficacy of ATII are needed to determine its role in the management of distributive shock.