Free-standing carboxymethyl cellulose film incorporating nanoformulated pomegranate extract for meat packaging.

This study aimed to explore an innovative approach to enhancing the shelf-life and quality of meat products through the application of an active packaging system. The study involved the development of new free-standing carboxymethyl cellulose (CMC) nanocomposite films incorporated with nanoencapsulated flavonoids derived from pomegranate extract. The loaded flavonoids, known for their antioxidant and antimicrobial properties, were nanoencapsulated via a self-assembly approach in a mixture of chitosan and sodium alginate to improve their stability, solubility, and controlled release characteristics. Chemical structure, size, and morphology of the obtained nanoparticles (Pg-NPs) were studied with FTIR, zeta-sizer, and TEM. The Pg-NPs showed particle size of 232 nm, and zeta-potential of -20.7 mV. Various free-standing nanocomposite films were then developed via incorporation of Pg-NPs into CMC-casted films. FTIR, SEM, thermal and mechanical properties, and surface wettability were intensively studied for the nanocomposite films. Barrier properties against water vapor were investigated at 2022 g·m-2d-1. The nanocomposite films possessed superior properties for inhibiting bacterial growth and extending the shelf-life of beef and poultry meat for 12 days compared with the Pg-NPs-free CMC films. This study presented a promising approach for development of active packaging systems with improved antimicrobial and antioxidant properties, and economic and environmental impacts.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Emergent external ventricular drain placement in patients with factor Xa inhibitor-associated intracerebral hemorrhage after reversal with andexanet alfa.

BACKGROUND: Andexanet alfa (AA), a factor Xa-inhibitor (FXi) reversal agent, is given as a bolus followed by a 2-hour infusion. This long administration time can delay EVD placement in intracerebral hemorrhage (ICH) patients. We sought to evaluate the safety of EVD placement immediately post-AA bolus compared to post-AA infusion. METHODS: We conducted a retrospective study that included adult patients admitted with FXi-associated ICH who received AA and underwent EVD placement The primary outcome was the occurrence of a new hemorrhage (tract, extra-axial, or intraventricular hemorrhage). Secondary outcomes included mortality, intensive care unit and hospital length of stay, and discharge modified Rankin Score. The primary safety outcome was documented thrombotic events. RESULTS: Twelve patients with FXi related ICH were included (EVD placement post-AA bolus, N = 8; EVD placement post-AA infusion, N = 4). Each arm included one patient with bilateral EVD placed. There was no difference in the incidence of new hemorrhages, with one post-AA bolus patient had small, focal, nonoperative extra-axial hemorrhage. Morbidity and mortality were higher in post-AA infusion patients (mRS, post-AA bolus, 4 [4-6] vs. post-AA infusion 6 [5,6], p = 0.24 and post-AA bolus, 3 (37.5 %) vs. post-AA infusion, 3 (75 %), p = 0.54, respectively). One patient in the post-AA bolus group had thrombotic event. There was no difference in hospital LOS (post-AA bolus, 19 days [12-26] vs. post-AA infusion, 14 days [9-22], p = 0.55) and ICU LOS (post-AA bolus, 10 days [6-13] vs. post-AA infusion, 11 days [5-21], p = 0.86). CONCLUSION: We report no differences in the incidence of tract hemorrhage, extra-axial hemorrhage, or intraventricular hemorrhage post-AA bolus versus post-AA infusion. Larger prospective studies to validate these results are warranted.

Neuropharmacology in the Intensive Care Unit.

Clinicians must individualize pharmacotherapy for patients with acute neurological injury based on multiple factors, including age, comorbidities, and chronic medication use. Many pharmacokinetic and pharmacodynamic properties are altered during acute illness, particularly absorption, distribution, metabolism, and elimination, which may result in loss of drug effect or toxicity. This article provides clinicians with general pharmacologic knowledge of the following drug regimens commonly prescribed to neurocritically ill adults: sedatives, analgesics, osmotherapy, antiseizure medications, antishivering agents, vasoactive agents, and antithrombotic reversal agents.

Narrative Review: Addressing Covid-19 Vaccine Concerns in Special and Vulnerable Populations.

Public health advocates and healthcare professionals (HCPs) have been challenged with vaccine hesitancy and addressing misinformation. In order for HCPs and pharmacists, in particular, to serve as effective stewards of COVID-19 vaccine science in the interest of the public good, it is imperative for HCPs to appreciate the various factors contributing to vaccine hesitancy and vaccine distrust. A PubMed search was performed and relevant articles on COVID-19 vaccine in populations of interest were included. Information from health agencies, such as the Centers for Disease Control and Prevention (CDC) as well as established professional health societies was incorporated for guidance. This review focuses on COVID-19 vaccine concerns in the populations of children, pregnancy and lactation, immunocompromised, and religious and ethnic disparities. We also discuss post emergency use authorization experience with respect to vaccine safety including annotations on Guillain-Barré Syndrome, myocarditis and pericarditis, and thrombosis with thrombocytopenia syndrome.

Timing of vasoactive agents and corticosteroid initiation in septic shock.

Septic shock remains a health care concern associated with significant morbidity and mortality. The Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock recommend early fluid resuscitation and antimicrobials. Beyond initial management, the guidelines do not provide clear recommendations on appropriate time to initiate vasoactive therapies and corticosteroids in patients who develop shock. This review summarizes the literature regarding time of initiation of these interventions. Clinical data regarding time of initiation of these therapies in relation to shock onset, sequence of treatments with regard to each other, and clinical markers evaluated to guide initiation are summarized. Early-high vasopressor initiation within first 6 h of shock onset is associated with lower mortality. Following norepinephrine initiation, the exact dose and timing of escalation to adjunctive vasopressor agents are not well elucidated in the literature. However, recent data indicate that timing may be an important factor in initiating vasopressors and adjunctive therapies, such as corticosteroids. Norepinephrine-equivalent dose and lactate concentration can aid in determining when to initiate vasopressin and angiotensin II in patients with septic shock. Future guidelines with clear recommendations on the time of initiation of septic shock therapies are warranted.

Relationship Between Glucose Time in Range in Diabetic and Non-Diabetic Patients and Mortality in Critically Ill Patients.

Background: Shorter time spent in specific blood glucose ranges is associated with mortality benefit in critically ill patients. However, various time in range values are reported, each based on a specific blood glucose range. Objective: To evaluate relationship between percentage of time spent at various blood glucose ranges (TIR) and mortality in critically ill patients. Methods: Single-center, retrospective, cohort study that included adult patients admitted to ICU for at least one day. We evaluated the relationship between TIR at prespecified blood glucose ranges and hospital mortality in diabetic and non-diabetic patients Results: Of the 5287 patients included, 3705 (70.0%) were non-diabetic and 1582 were diabetic (29.9%). Diabetic patients had higher in-hospital mortality rate (15.8%) compared to non-diabetic patients (11.3%), p < 0.0001, and with higher incidence of hyperglycemia (77.8% vs. 39.4%) and hypoglycemia (14.3% vs. 10%) compared to non-diabetic patients, p < 0.0001. The highest median TIR for both diabetic [76% (49.1 - 97.8%)] and non-diabetic patients [100% (92.3--100%)] was at blood glucose range of 70-180 mg/dL. In non-diabetic cohort, the only optimal TIR of 40% at blood glucose range of 70-120 mg/dL was identified. Non-diabetic patients stratified into TIR 70-120 mg/dL > 40% reported significantly lower mortality (7.0%) rate compared to patients with TIR 70-120 mg/dL < 40% (15.7%), OR 0.52, 95% CI 0.27-0.97, adjusted-p = 0.03. In diabetic patients, no relationship was detected between TIR at all predefined glucose ranges and hospital mortality. Conclusion: Critically ill non-diabetic patients who spent at least 40% of time in blood glucose range of 70-120 mg/dL had improved survival. This association was not observed in diabetic patients.

Use of droxidopa for blood pressure augmentation after acute spinal cord injury: case reports.

Hypotension secondary to autonomic dysfunction is a common complication of acute spinal cord injury (SCI) that may worsen neurologic outcomes. Midodrine, an enteral α-1 agonist, is often used to facilitate weaning intravenous (IV) vasopressors, but its use can be limited by reflex bradycardia. Alternative enteral agents to facilitate this wean in the acute post-SCI setting have not been described. We aim to describe novel application of droxidopa, an enteral precursor of norepinephrine that is approved to treat neurogenic orthostatic hypotension, in the acute post-SCI setting. Droxidopa may be an alternative enteral therapy for those intolerant of midodrine due to reflex bradycardia. We describe two patients suffering traumatic cervical SCI who were successfully weaned off IV vasopressors with droxidopa after failing with midodrine. The first patient was a 64-year-old male who underwent C3-6 laminectomies and fusion after a ten-foot fall resulting in quadriparesis. Post-operatively, the addition of midodrine in an attempt to wean off IV vasopressors resulted in significant reflexive bradycardia. Treatment with droxidopa facilitated rapidly weaning IV vasopressors and transfer to a lower level of care within 72 hours of treatment initiation. The second patient was a 73-year-old male who underwent C3-5 laminectomies and fusion for a traumatic hyperflexion injury causing paraplegia. The addition of midodrine resulted in severe bradycardia, prompting consideration of pacemaker placement. However, with the addition of droxidopa, this was avoided, and the patient was weaned off IV vasopressors on dual oral therapy with midodrine and droxidopa. Droxidopa may be a viable enteral therapy to treat hypotension in patients after acute SCI who are otherwise not tolerating midodrine in order to wean off IV vasopressors. This strategy may avoid pacemaker placement and facilitate shorter stays in the intensive care unit, particularly for patients who are stable but require continued intensive care unit admission for IV vasopressors, which can be cost ineffective and human resource depleting.

Vitamin C for Sepsis and Septic Shock.

BACKGROUND: Sepsis remains a leading cause of death in the critically ill. The combination of thiamine, vitamin C, and hydrocortisone has recently emerged as a potential adjunctive therapy and supportive care for patients with sepsis and septic shock. AREAS OF UNCERTAINTY: Several randomized and observational controlled trials evaluated the role of vitamin C in sepsis and septic shock. However, there are variabilities in the findings of these studies that led to a substantial global debate on incorporating vitamin C therapy in clinical practice. DATA SOURCES: A PubMed and Embase English language literature search through April 2021 was performed using the following terms: ascorbic acid, vitamin C, corticosteroid, hydrocortisone, thiamine, HAT, sepsis, and shock. Citations, including controlled trials, observational studies, review articles, guidelines, and consensus statements, were reviewed. The risk of bias for each clinical study was systematically evaluated. Relevant clinical data focusing on efficacy, safety, and special considerations regarding the use of vitamin C with and without thiamine and hydrocortisone in sepsis and septic shock were narratively summarized. RESULTS: The most commonly used vitamin C dosing in sepsis and septic shock is 1.5 g every 6 hours with and without thiamine and hydrocortisone. Current literature is limited because of heterogeneity in vitamin C regimen used, initiation time, and duration of treatment. This limitation led to variability in outcomes evaluated. Vitamin C decreases proinflammatory mediators and slows the progression of endothelial injury in severe sepsis. There is an inconsistency between randomized controlled trials and observational controlled trials regarding mortality, resolution in organ failure, hospital and intensive care unit length of stay findings with the use of vitamin C in septic shock. Vitamin C seems to be safe in comparison with placebo. CONCLUSIONS: Future studies with consistent end points, initiation time with an emphasis on early initiation, and standard vitamin C dosing regimen are needed to determine the overall benefit of vitamin C in sepsis.

Pharmacists leadership in a medication shortage response: Illustrative examples from a health system response to the COVID-19 crisis.

As medication experts, clinical pharmacists play an active and dynamic role in a medication shortage response. Supplementing existing guidelines with an actionable framework of discrete activities to support effective medication shortage responses can expand the scope of pharmacy practice and improve patient care. Dissemination of best practices and illustrative, networked examples from health systems can support the adoption of innovative solutions. In this descriptive report, we document the translation of published shortage mitigation guidelines into system success through broad pharmacist engagement and the adaption and implementation of targeted strategies. The profound, wide-reaching medication shortages that accompanied the coronavirus disease 2019 (COVID-19) pandemic are used to highlight coordinated but distinct practices and how they have been combined to expand the influence of the pharmacy enterprise.

Andexanet Alfa Versus 4-Factor Prothrombin Complex Concentrate for Reversal of Factor Xa Inhibitors in Intracranial Hemorrhage.

BACKGROUND/OBJECTIVE: There are limited data on the risks and benefits of using andexanet alfa (AA) in comparison with four-factor prothrombin complex concentrate (4F-PCC) to reverse factor Xa inhibitors (FXi) associated intracranial hemorrhage (ICH). We sought to describe our experience with AA or 4F-PCC in patients with oral FXi-related traumatic and spontaneous ICH. METHODS: We conducted a retrospective review of consecutive adult patients with FXi-related ICH who received AA or 4F-PCC. FXi-related ICH cases included traumatic and spontaneous intracranial hemorrhages. Our primary analysis evaluated ICH stability on head computed tomography scan (CT), defined as a similar amount of blood from the initial scan at the onset of ICH to subsequent scans, at 6-h and 24-h post-administration of AA or 4F-PCC. For the subset of spontaneous intraparenchymal hemorrhages, volume was measured at 6-h and 24-h post-reversal. In secondary analyses, we evaluated good functional outcome at discharge, defined as a Modified Rankin Score of less than 3, and the incidence of thrombotic events after AA or 4F-PCC adminstration, during hospitalization. RESULTS: A total of 44 patients (16 traumatic and 28 spontaneous ICH) with median age of 79 years [72-86], 36% females, with a FXi-related ICH, were included in this study. The majority of spontaneous ICHs were intraparenchymal 19 (68%). Twenty-eight patients (64%) received AA and 16 patients (36%) received 4F-PCC. There was no difference between AA and 4F-PCC in terms of CT stability at 6 h (21 [78%] vs 10 [71%], p = 0.71) and 24 h (15 [88%] vs 6 [60%], p = 0.15). In a subgroup of patients with spontaneous intraparenchymal hemorrhage, there was no difference in the degree of achieved hemostasis based on hematoma volume between AA and 4F-PCC at 6 h (9.3 mL [6.9-26.4] vs 10 mL [9.4-22.1], adjusted p = 0. 997) and 24-h (9.2 mL [6.1-18.8] vs 9.9 [9.4-21.1], adjusted p = 1). The number of patients with good outcome based on mRS on discharge were 10 (36%) and 6 (38%) in the AA and 4F-PCC groups, respectively (adjusted p = 0.81). The incidence of thromboembolic events was similar in the AA and 4F-PCC groups (2 [7%] vs 0, p = 0.53). CONCLUSION: In this limited sample of patients, we found no difference in neuroimaging stability, functional outcome and thrombotic events when comparing AA and 4F-PCC in patients with FXi-related ICH. Since our analysis is likely underpowered, a multi-center collaborative network devoted to this question is warranted.

Phenobarbital Monotherapy for the Management of Alcohol Withdrawal Syndrome in Surgical-Trauma Patients.

BACKGROUND: Benzodiazepine is first-line therapy for alcohol withdrawal syndrome (AWS), and phenobarbital is an alternative therapy. However, its use has not been well validated in the surgical-trauma patient population. OBJECTIVE: To describe the use of fixed-dose phenobarbital monotherapy for the management of patients at risk for AWS in the surgical-trauma intensive care unit. METHODS: Surgical-trauma critically ill patients who received phenobarbital monotherapy, loading dose followed by a taper regimen, for the management of AWS were included in this evaluation. The effectiveness of phenobarbital monotherapy to treat AWS and prevent development of AWS-related complications were evaluated. Safety end points assessed included significant hypotension, bradycardia, respiratory depression, and need for invasive mechanical ventilation. RESULTS: A total of 31 patients received phenobarbital monotherapy; the majority of patients were at moderate risk for developing AWS (n = 20; 65%) versus high risk (n = 11; 35%). None of the patients developed AWS-related complications; all patients were successfully managed for their AWS. Nine patients (29%) received nonbenzodiazepine adjunct therapy for agitation post-phenobarbital initiation. Three patients (10%) experienced hypotension, and 3 (10%) were intubated. None of the patients had clinically significant bradycardia or respiratory depression. CONCLUSION AND RELEVANCE: Fixed-dose phenobarbital monotherapy appears to be well tolerated and effective in the management of AWS. Further evaluation is needed to determine the extent of benefit with the use of phenobarbital monotherapy for management of AWS.

Sedation, Analgesia, and Paralysis in COVID-19 Patients in the Setting of Drug Shortages.

The rapid spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a global pandemic. The 2019 coronavirus disease (COVID-19) presents with a spectrum of symptoms ranging from mild to critical illness requiring intensive care unit (ICU) admission. Acute respiratory distress syndrome is a major complication in patients with severe COVID-19 disease. Currently, there are no recognized pharmacological therapies for COVID-19. However, a large number of COVID-19 patients require respiratory support, with a high percentage requiring invasive ventilation. The rapid spread of the infection has led to a surge in the rate of hospitalizations and ICU admissions, which created a challenge to public health, research, and medical communities. The high demand for several therapies, including sedatives, analgesics, and paralytics, that are often utilized in the care of COVID-19 patients requiring mechanical ventilation, has created pressure on the supply chain resulting in shortages in these critical medications. This has led clinicians to develop conservation strategies and explore alternative therapies for sedation, analgesia, and paralysis in COVID-19 patients. Several of these alternative approaches have demonstrated acceptable levels of sedation, analgesia, and paralysis in different settings but they are not commonly used in the ICU. Additionally, they have unique pharmaceutical properties, limitations, and adverse effects. This narrative review summarizes the literature on alternative drug therapies for the management of sedation, analgesia, and paralysis in COVID-19 patients. Also, this document serves as a resource for clinicians in current and future respiratory illness pandemics in the setting of drug shortages.

Intravenous brivaracetam for the management of refractory focal non-convulsive status epilepticus.

Diagnosis and management of status epilepticus (SE), including non-convulsive status epilepticus (NCSE), is challenging, with a reported 30%-50% of epilepticus patients not responding to available antiseizure medications (ASMs). Injectable benzodiazepines, fosphenytoin, valproate, levetiracetam, lacosamide and phenobarbital are commonly used for treating SE. Brivaracetam, a new ASM, with higher affinity and greater selectivity for the synaptic vesicle glycoprotein 2A than levetiracetam, has been approved as monotherapy or adjunct for treatment of focal onset seizures. Brivaracetam may have a role in the management of SE. However, limited data exist on brivaracetam's efficacy in SE. We describe a patient case with focal NCSE refractory to levetiracetam, fosphenytoin, lacosamide and valproate who demonstrated clinical and electrographic improvement on continuous electroencephalography monitoring after brivaracetam administration.

Evaluation of Vasopressor Exposure and Mortality in Patients With Septic Shock.

OBJECTIVES: The objectives of this study were to: 1) determine the association between vasopressor dosing intensity during the first 6 hours and first 24 hours after the onset of septic shock and 30-day in-hospital mortality; 2) determine whether the effect of vasopressor dosing intensity varies by fluid resuscitation volume; and 3) determine whether the effect of vasopressor dosing intensity varies by dosing titration pattern. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. Vasopressor dosing intensity was defined as the total vasopressor dose infused across all vasopressors in norepinephrine equivalents. SETTING: Thirty-three hospital sites in the United States (n = 32) and Jordan (n = 1). PATIENTS: Consecutive adults requiring admission to the ICU with septic shock treated with greater than or equal to 1 vasopressor within 24 hours of shock onset. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 1,639 patients screened, 616 were included. Norepinephrine (93%) was the most common vasopressor. Patients received a median of 3,400 mL (interquartile range, 1,851-5,338 mL) during the 24 hours after shock diagnosis. The median vasopressor dosing intensity during the first 24 hours of shock onset was 8.5 µg/min norepinephrine equivalents (3.4-18.1 µg/min norepinephrine equivalents). In the first 6 hours, increasing vasopressor dosing intensity was associated with increased odds ratio of 30-day in-hospital mortality, with the strength of association dependent on concomitant fluid administration. Over the entire 24 hour period, every 10 µg/min increase in vasopressor dosing intensity was associated with an increased risk of 30-day mortality (adjusted odds ratio, 1.33; 95% CI, 1.16-1.53), and this association did not vary with the amount of fluid administration. Compared to an early high/late low vasopressor dosing strategy, an early low/late high or sustained high vasopressor dosing strategy was associated with higher mortality. CONCLUSIONS: Increasing vasopressor dosing intensity during the first 24 hours after septic shock was associated with increased mortality. This association varied with the amount of early fluid administration and the timing of vasopressor titration.

Variation in Fluid and Vasopressor Use in Shock With and Without Physiologic Assessment: A Multicenter Observational Study.

OBJECTIVES: To characterize the association between the use of physiologic assessment (central venous pressure, pulmonary artery occlusion pressure, stroke volume variation, pulse pressure variation, passive leg raise test, and critical care ultrasound) with fluid and vasopressor administration 24 hours after shock onset and with in-hospital mortality. DESIGN: Multicenter prospective cohort study between September 2017 and February 2018. SETTINGS: Thirty-four hospitals in the United States and Jordan. PATIENTS: Consecutive adult patients requiring admission to the ICU with systolic blood pressure less than or equal to 90 mm Hg, mean arterial blood pressure less than or equal to 65 mm Hg, or need for vasopressor. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 1,639 patients enrolled, 39% had physiologic assessments. Use of physiologic assessment was not associated with cumulative fluid administered within 24 hours of shock onset, after accounting for baseline characteristics, etiology and location of shock, ICU types, Acute Physiology and Chronic Health Evaluation III, and hospital (beta coefficient, 0.04; 95% CI, -0.07 to 0.15). In multivariate analysis, the use of physiologic assessment was associated with a higher likelihood of vasopressor use (adjusted odds ratio, 1.98; 95% CI, 1.45-2.71) and higher 24-hour cumulative vasopressor dosing as norepinephrine equivalent (beta coefficient, 0.37; 95% CI, 0.19-0.55). The use of vasopressor was associated with increased odds of in-hospital mortality (adjusted odds ratio, 1.88; 95% CI, 1.27-2.78). In-hospital mortality was not associated with the use of physiologic assessment (adjusted odds ratio, 0.86; 95% CI, 0.63-1.18). CONCLUSIONS: The use of physiologic assessment in the 24 hours after shock onset is associated with increased use of vasopressor but not with fluid administration.

Application of Cannabinoids in Neurosciences: Considerations and Implications.

Medicinal cannabinoid use continues to evolve across the United States, although legitimate federal recognition for medicinal purpose is lacking. Variability exists across states within the United States with respect to legislation, and health care institutions encounter challenges when patients present with a history of medicinal cannabinoid use. Emerging evidence in the field of neurosciences suggests a role of cannabinoids for neurologic medical conditions such as Parkinson disease, multiple sclerosis, and epilepsy. We aim to provide an overview of cannabinoids including a historical perspective, pharmacology, applications in neurosciences, and challenges in health care and academia. Knowledge of the appropriate role of cannabinoids in the clinical setting is essential for all health care practitioners including nursing.

Narrative Review of Controversies Involving Vasopressin Use in Septic Shock and Practical Considerations.

Objective: To summarize literature evaluating vasopressin use, focusing on clinical controversies regarding initiation, dosing, and discontinuation and interaction of vasopressin with other therapies in septic shock patients. Data Sources: A PubMed English-language literature search (January 2008 to December 2019) was performed using these terms: arginine vasopressin, septic, shock, and sepsis. Citations, including controlled trials, observational studies, review articles, guidelines, and consensus statements, were reviewed. Study Selection and Data Extraction: Relevant clinical data focusing on specific controversial questions regarding the utility of vasopressin in patients with septic shock were narratively summarized. Data Synthesis: Current literature does not strongly support the use of vasopressin as a first-line initial therapy for septic shock. Additionally, there are conflicting data for weight-based dosing of vasopressin in overweight patients. Evidence for vasopressin renal protection and interaction with corticosteroids is minimal. However, vasopressin has the ability to reduce catecholamine requirements in septic shock patients and may provide a mortality benefit in specific subgroups. Discontinuation of vasopressin last, not second to last, in resolving septic shock may reduce hypotension development. Relevance to Patient Care and Clinical Practice: This review addresses specific clinical controversies that drive vasopressin use in septic shock patients in real-world practice. Conclusion: Vasopressin should remain second-line adjunct to norepinephrine to augment mean arterial pressures. Dosing should be initiated at 0.03 U/min, and higher doses offer minimal benefit. There are conflicting data on the impact of weight on vasopressin response. Studies have failed to show renal benefit with vasopressin use or an interaction with corticosteroid therapy.

Vasopressin Plasma Concentrations Are Not Associated with Hemodynamic Response to Exogenous Vasopressin for Septic Shock.

INTRODUCTION: Positive hemodynamic response to vasopressin after 6 hours of infusion was independently associated with lower mortality in a previous retrospective study of patients with septic shock. However, factors previously associated with higher plasma vasopressin concentration were not associated with response, and the relationship between plasma vasopressin concentration and hemodynamic response has not been evaluated. OBJECTIVES: This cross-sectional study compared plasma vasopressin concentrations in hemodynamic responders and nonresponders to vasopressin in patients with septic shock to evaluate plasma vasopressin concentration as a therapeutic target for hemodynamic response to vasopressin. METHODS: Adult patients with septic shock were included if they were treated with fixed-dose vasopressin as an adjunct to catecholamines for at least 3 hours. Patients were assigned to groups based on vasopressin response. RESULTS: Ten hemodynamic responders to vasopressin and eight nonresponders were included. Blood samples for plasma vasopressin concentration were collected 3-6 hours after vasopressin initiation. Baseline characteristics were similar between groups. No difference was detected in plasma vasopressin concentrations between hemodynamic responders and nonresponders (median 88.6 pg/ml [interquartile range (IQR) 84.4-107.5 pg/ml] vs 89.9 pg/ml [IQR 67.5-157.4 pg/ml], p=0.79, respectively). We also did not detect a difference between groups after correcting for vasopressin dose; median vasopressin plasma concentration per 0.01 units/minute of vasopressin infusion for responders was 25.9 pg/ml (IQR 21.8-31.8 pg/ml) versus 29.5 pg/ml (IQR 23.0-57.5 pg/ml, p=0.48) for nonresponders. No difference in clinical outcomes was detected between groups. The findings were robust to multiple sensitivity analyses. CONCLUSIONS: This study does not support the use of plasma vasopressin concentrations as a therapeutic target to predict hemodynamic response to exogenous vasopressin in septic shock.