Impact of a Pharmacist-Driven Medication Diluent Volume Optimization Protocol on Fluid Balance and Outcomes in Critically Ill Patients.

Background: Volume overload (VO) is common in the intensive care unit (ICU) and associated with negative outcomes. Approaches have been investigated to curtail VO; however, none specifically focused on medication diluent volume optimization. Objective: Investigate the impact of a pharmacist-driven medication diluent volume optimization protocol on fluid balance in critically ill patients. Methods: A prospective, pilot study was conducted in a medical ICU during October 2021 to December 2021 (pre) and February 2022 to April 2022 (post). A pharmacist-driven medication diluent volume optimization protocol focusing on vasopressor and antimicrobial diluent volumes was implemented. Demographics and clinical data were collected during ICU admission up to 7 days. The primary outcome was net fluid balance on day 3. Secondary outcomes were medication volumes administered, net fluid balance, ICU length of stay, and mortality. Results: Supply chain shortages caused the study to stop at the end of February 2022. Overall, 152 patients were included (123 pre group, 29 post group). The most common admission diagnosis was acute respiratory failure (35%). Vasopressors and antimicrobials were utilized in 47% and 66% of patients, respectively. Net fluid balance on day 3 was greater but not significant in the post group (227.1 mL [-1840.3 to 3483.7] vs 2012.3 mL [-2686.0 to 4846.0]; P = .584). Antimicrobial diluent volumes were significantly less in the post group. No differences were seen in other secondary outcomes. Protocol group assignment was not associated with net fluid balance on day 3. Conclusion: Despite decreasing antimicrobial volume contributions, optimizing diluent volumes alone did not significantly impact overall volume status. Future studies should focus on comprehensive approaches to medication diluent optimization and fluid stewardship.

Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline.

Background: This American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana de Tórax guideline updates prior idiopathic pulmonary fibrosis (IPF) guidelines and addresses the progression of pulmonary fibrosis in patients with interstitial lung diseases (ILDs) other than IPF. Methods: A committee was composed of multidisciplinary experts in ILD, methodologists, and patient representatives. 1) Update of IPF: Radiological and histopathological criteria for IPF were updated by consensus. Questions about transbronchial lung cryobiopsy, genomic classifier testing, antacid medication, and antireflux surgery were informed by systematic reviews and answered with evidence-based recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. 2) Progressive pulmonary fibrosis (PPF): PPF was defined, and then radiological and physiological criteria for PPF were determined by consensus. Questions about pirfenidone and nintedanib were informed by systematic reviews and answered with evidence-based recommendations using the GRADE approach. Results:1) Update of IPF: A conditional recommendation was made to regard transbronchial lung cryobiopsy as an acceptable alternative to surgical lung biopsy in centers with appropriate expertise. No recommendation was made for or against genomic classifier testing. Conditional recommendations were made against antacid medication and antireflux surgery for the treatment of IPF. 2) PPF: PPF was defined as at least two of three criteria (worsening symptoms, radiological progression, and physiological progression) occurring within the past year with no alternative explanation in a patient with an ILD other than IPF. A conditional recommendation was made for nintedanib, and additional research into pirfenidone was recommended. Conclusions: The conditional recommendations in this guideline are intended to provide the basis for rational, informed decisions by clinicians.

Contemporary targeted temperature management: Clinical evidence and controversies.

Advancements in cardiac arrest and post-cardiac arrest care have led to improved survival to hospital discharge. While survival to hospital discharge is an important clinical outcome, neurologic recovery is also a priority. With the advancement of targeted temperature management (TTM), the American Heart Association guidelines for post-cardiac arrest care recommend TTM in patients who remain comatose after return of spontaneous circulation (ROSC). Recently, the TTM2 randomized controlled trial found no significant difference in neurologic function and mortality at 6-months between traditional hypothermia to 33°C versus 37.5°C. While TTM has been evaluated for decades, current literature suggests that the use of TTM to 33° when compared to a protocol of targeted normothermia does not result in improved outcomes. Instead, perhaps active avoidance of fever may be most beneficial. Extracorporeal cardiopulmonary resuscitation and membrane oxygenation can provide a means of both hemodynamic support and TTM after ROSC. This review aims to describe the pathophysiology, physiologic aspects, clinical trial evidence, changes in post-cardiac arrest care, potential risks, as well as controversies of TTM.

Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: A Systematic Review and Meta-Analysis.

OBJECTIVES: Critically ill patients routinely receive vancomycin as empiric antibiotic therapy. A continuous infusion administration strategy may be superior to intermittent infusion by minimizing peak concentrations and variability thereby optimizing safety. We performed a systematic review and meta-analysis to investigate the impact of vancomycin infusion strategy on acute kidney injury in critically ill adults. DATA SOURCES: A systematic search of MEDLINE, CINAHL, Web of Science, International Pharmaceutical Abstracts, and Google Scholar was undertaken. STUDY SELECTION: We included randomized controlled trials and observational studies evaluating acute kidney injury in critically ill adults comparing vancomycin administered by intermittent and continuous infusion. Secondary outcomes included mortality and pharmacokinetic target attainment. DATA EXTRACTION: Eleven studies were identified for analysis with baseline demographics, endpoints, protocol definitions, and outcomes extracted. DATA SYNTHESIS: When compared with intermittent infusion, continuous infusion was associated with a reduction in acute kidney injury in critically ill adults (odds ratio, 0.47; 95% CI, 0.34-0.65) and a 2.6 greater odds of pharmacokinetic target attainment (odds ratio, 2.63; 95% CI, 1.52-4.57). No difference in mortality was observed (odds ratio, 1.04; 95% CI, 0.80-1.35). CONCLUSIONS: When administered via a continuous infusion, vancomycin is associated with a 53% reduction in the odds of acute kidney injury and a 2.6-fold higher odds of pharmacokinetic target attainment when compared with intermittent infusion without influencing overall mortality.

Pathophysiology of Volume Administration in Septic Shock and the Role of the Clinical Pharmacist.

Objective: To review physiological rationale and evidence base surrounding fluid harm to prepare the clinical pharmacist for accountability regarding volume-related outcomes. Data Sources: A PubMed/MEDLINE search was conducted using the following terms: (fluid therapy) AND [(critical care) OR (sepsis)] from 1966 to August 2019 published in English. Study Selection and Data Extraction: A total of 3364 citations were reviewed with only relevant clinical data extracted. Data Synthesis: Although early fluid resuscitation may be a necessary component to decrease mortality in the majority of patients with septic shock admitted to the intensive care unit (ICU), the benefit of continued administration after the first 24 hours is uncertain. Paradoxically, a positive fluid balance secondary to intravenous fluid receipt has been associated with diverse and perpetuating detriment on a multitude of organ systems after the first 24 hours of ICU stay. Continued clinical harm has been demonstrated on patient outcomes such as rates of mortality and length of stay. Despite the growing body of evidence supporting the potential adverse aspects of positive fluid balance, fluid overload remains common during critical care admission. Conclusion: Physiological concerns to overly zealous fluid administration and subsequent volume overload are vast. Relevance to Patient Care and Clinical Practice: Optimization of fluid balance in critically ill patients with sepsis is primed for clinical pharmacy intervention. Critical care pharmacists have the potential to improve patient care by optimizing fluid pharmacotherapy while potentially reducing adverse events, days on mechanical ventilation, and length of ICU stay.

To Block or Not: Updates in Neuromuscular Blockade in Acute Respiratory Distress Syndrome.

Objective: To review and evaluate neuromuscular blocking agents (NMBAs) in critically ill patients with acute respiratory distress syndrome (ARDS). Data Sources: A literature search utilizing PubMed was performed (January 1991 to January 2020) using the following search terms: (neuromuscular blocking agents OR neuromuscular blockade OR cisatracurium OR rocuronium OR vecuronium OR pancuronium OR atracurium) AND *acute respiratory distress syndrome OR acute lung injury). Publications in English were evaluated. Study Selection and Data Extraction: Relevant clinical studies in humans were considered. Data Synthesis: Although NMBAs have been used for decades in the setting of ARDS, questions regarding mortality benefit remain. Early NMBA, within 48 hours of lung injury, have been historically used in critically ill patients with ARDS to aid in increasing alveolar recruitment, improving patient-ventilator synchrony, and promoting oxygenation by the prevention of contraction of respiratory muscles. Until recently, the literature showed an improvement in 90-day adjusted mortality. However, recent literature has demonstrated the lack of a mortality benefit. The continued receipt of NMBAs, with no clear benefit, could potentially lead to increased costs, skin breakdown, corneal abrasions, venous thromboembolisms, intensive care unit acquired weakness, and awareness with inappropriate sedation. Relevance to Patient Care and Clinical Practice: This review aims at discussing the preferred NMBA based on mechanism of action and reviews specific clinical trial data for the use of NMBAs in ARDS, clinical implications of these trial data, complications for the use of NMBAs, and needed future directions. Conclusions: The mortality benefit of NMBAs in ARDS has contradicting evidence with potentially serious adverse effects and notable controversies.

Impact of protocolized diuresis for de-resuscitation in the intensive care unit.

OBJECTIVE: Administration of diuretics has been shown to assist fluid management and improve clinical outcomes in the critically ill post-shock resolution. Current guidelines have not yet included standardization or guidance for diuretic-based de-resuscitation in critically ill patients. This study aimed to evaluate the impact of a multi-disciplinary protocol for diuresis-guided de-resuscitation in the critically ill. METHODS: This was a pre-post single-center pilot study within the medical intensive care unit (ICU) of a large academic medical center. Adult patients admitted to the Medical ICU receiving mechanical ventilation with either (1) clinical signs of volume overload via chest radiography or physical exam or (2) any cumulative fluid balance ≥ 0 mL since hospital admission were eligible for inclusion. Patients received diuresis per clinician discretion for a 2-year period (historical control) followed by a diuresis protocol for 1 year (intervention). Patients within the intervention group were matched in a 1:3 ratio with those from the historical cohort who met the study inclusion and exclusion criteria. RESULTS: A total of 364 patients were included, 91 in the protocol group and 273 receiving standard care. Protocolized diuresis was associated with a significant decrease in 72-h post-shock cumulative fluid balance [median, IQR - 2257 (- 5676-920) mL vs 265 (- 2283-3025) mL; p < 0.0001]. In-hospital mortality in the intervention group was lower compared to the historical group (5.5% vs 16.1%; p = 0.008) and higher ICU-free days (p = 0.03). However, no statistically significant difference was found in ventilator-free days, and increased rates of hypernatremia and hypokalemia were demonstrated. CONCLUSIONS: This study showed that a protocol for diuresis for de-resuscitation can significantly improve 72-h post-shock fluid balance with potential benefit on clinical outcomes.

Evaluation of Continuous Infusion Vancomycin Administration in a Critically Ill Trauma Population.

Vancomycin is a first-line antibiotic for empiric treatment of gram-positive infections in the trauma intensive care unit. When dosed intermittently, difficulties arise from trough collection and drug monitoring. The objective of this study was to evaluate time to goal vancomycin levels comparing a continuous infusion protocol when compared to standard intermittent infusion dosing. This was a retrospective cohort of patients admitted to the trauma intensive care unit between July 2011 and July 2015 receiving vancomycin for at least 48 hours. In this cohort of 150 patients, continuous infusion vancomycin had a decreased time to goal vancomycin level (2.5 vs 3.8 days, P ≤ .05) with a higher incidence of target attainment (60% vs 40%, P ≤ .05). This reflected in a decrease in average number of blood samples per patient (1 vs 3, P ≤ .05) and shorter duration of therapy (3.8 vs 6.8 days, P ≤ .05). Patients receiving continuous infusion vancomycin also experienced less nephrotoxicity (21% vs 43%, P ≤ .05). Patients in the intermittent infusion group had more missed levels and doses, with only 1 in every 3 patients receiving all intended doses on time. Vancomycin continuous infusion resulted in a decrease in time to goal therapeutic vancomycin levels, number of blood samples required, and therapy duration. Larger trials are needed to validate these outcomes in broad patient groups and to validate the clinical implication and potential cost savings of these results.

Sensitizing the interdisciplinary team to desensitizations: An alemtuzumab case report.

INTRODUCTION: We describe a case of alemtuzumab (Campath®) hypersensitivity requiring desensitization within the medical intensive care unit (MICU) in a patient with T-cell prolymphocytic leukemia. CASE REPORT: We adopted a desensitization protocol from Gutierrez-Fernandez et al., which included three aliquots (0.15 mg intravenously (IV), 1.5 mg IV, and 28.5 mg IV) given approximately 1 h apart on day 1 followed by a full 30 mg dose IV on day 3. Unlike prior attempts to administer alemtuzumab to this patient, she tolerated the medication well and did not require any rescue medications. MANAGEMENT AND OUTCOME: Successful plan development required a significant amount of strategic communication between hematology/oncology and MICU-related physicians, pharmacists, and nurses to ensure a safe and effective desensitization. The first step of planning required creation of a desensitization order set with directions for medication preparation and administration, premedications, and available medications in the event of an adverse reaction or anaphylaxis. Anaphylactoid-related medications were prepared at bedside and ready for administration prior to beginning the desensitization. Alemtuzumab was compounded in a chemotherapy-certified hood and verified by at least two chemotherapy-certified pharmacists. Foreword planning was also necessary to ensure multiple people were available or present at bedside for the desensitization, including a chemotherapy-certified nurse, a second chemotherapy-certified nurse for verification, a critical care-certified pharmacist, a pulmonary/critical care attending physician, and hematology attending physician. DISCUSSION: This case exemplifies the importance of clear and coordinated communication between different healthcare fields to safely and effectively complete extensive protocols such as desensitization strategies.

Tracing the Lines: A Review of Viscoelastography for Emergency Medicine Clinicians.

BACKGROUND: Viscoelastography (VE) is an established method to identify coagulopathies in various disease processes. Clinical decisions can be made with real-time tracings and quantitative values at the bedside. Thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®) have been utilized in several disease states with clinical varying success. OBJECTIVES: This review will summarize the literature and provide recommendations pertaining to major disease processes where VE may be beneficial, including trauma, anticoagulation reversal, liver disease, acute ischemic stroke, and acquired brain injuries. DISCUSSION: VE has a role in many emergency medicine patients encountered by clinicians. Reduced mortality, decreased blood product utilization, and prognostication ability makes VE an intriguing tool that can be utilized by providers to improve patient care. CONCLUSION: This review serves as a way for emergency medicine clinicians to utilize VE in their practice and provides an insightful literature overview.

Fluid Overload Associates With Major Adverse Kidney Events in Critically Ill Patients With Acute Kidney Injury Requiring Continuous Renal Replacement Therapy.

OBJECTIVES: We examined the association between fluid overload and major adverse kidney events in critically ill patients requiring continuous renal replacement therapy for acute kidney injury. DESIGN: Retrospective cohort study. SETTING: ICU in a tertiary medical center. PATIENTS: Four-hundred eighty-one critically ill adults requiring continuous renal replacement therapy for acute kidney injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fluid overload was assessed as fluid balance from admission to continuous renal replacement therapy initiation, adjusted for body weight. Major adverse kidney events were defined as a composite of mortality, renal replacement therapy-dependence or inability to recover 50% of baseline estimated glomerular filtration rate (if not on renal replacement therapy) evaluated up to 90 days after discharge. Patients with fluid overload less than or equal to 10% were less likely to experience major adverse kidney events than those with fluid overload greater than 10% (71.6% vs 79.4%; p = 0.047). Multivariable logistic regression showed that fluid overload greater than 10% was associated with a 58% increased odds of major adverse kidney events (p = 0.046), even after adjusting for timing of continuous renal replacement therapy initiation. There was also a 2.7% increased odds of major adverse kidney events for every 1 day increase from ICU admission to continuous renal replacement therapy initiation (p = 0.024). Fluid overload greater than 10% was also found to be independently associated with an 82% increased odds of hospital mortality (p = 0.004) and 2.5 fewer ventilator-free days (p = 0.044), compared with fluid overload less than or equal to 10%. CONCLUSIONS: In critically ill patients with acute kidney injury requiring continuous renal replacement therapy, greater than 10% fluid overload was associated with higher risk of 90-day major adverse kidney events, including mortality and decreased renal recovery. Increased time between ICU admission and continuous renal replacement therapy initiation was also associated with decreased renal recovery. Fluid overload represents a potentially modifiable risk factor, independent of timing of continuous renal replacement therapy initiation, that should be further examined in interventional studies.

Hemodynamic Instability Secondary to Vasopressin Withdrawal in Septic Shock.

RATIONALE: Vasopressors such as norepinephrine are first line for support of mean arterial pressure (MAP) in the management of septic shock. Their use, however, is commonly associated with many adverse events. These detriments frequently trigger the use of alternative, noncatecholamine therapies, including vasopressin. Vasopressin deficiency is a known physiologic consequence of septic shock, and while guidelines recommend vasopressin in addition to norepinephrine, no consensus exists on the duration of deficiency or ideal time of cessation. Studies have suggested that vasopressin discontinuation prior to other vasopressors may lead to hypotension; however, data are limited. This study evaluates the optimal sequence for the discontinuation of vasopressin therapy in septic shock. METHODS: This was a 1-year retrospective study of 152 patients admitted to the medical intensive care unit (ICU) with septic shock who received concurrent norepinephrine and vasopressin for vasoactive support. Patients were excluded if death occurred on vasopressors, within 24 hours after discontinuation of vasopressors, or within 48 hours of ICU admission. The primary outcome of hemodynamic instability included incidence of hypotension after vasopressor discontinuation (2 consecutive MAPs < 60 mm Hg), fluid bolus administration, greater than 0.05 µg/kg/min increase in norepinephrine requirements, or addition of an alternative vasopressor. Secondary outcomes included time to hypotension, total vasopressor duration, arrhythmias, mortality, and length of stay. RESULTS: Ninety-one patients met exclusion criteria, resulting in 61 patients for evaluation. Vasopressin was the first vasoactive therapy to be discontinued in 19 patients and last in 42 patients. Baseline characteristics and the use of potentially confounding treatments known to effect MAP were similar between groups. Discontinuation of vasopressin first was associated with a significant increase in hemodynamic instability (74% vs 16.7%, P < .01), with a shorter time to hemodynamic instability (5 vs 15 hours, P < .01). Secondary outcomes were similar. CONCLUSION: Vasopressin discontinuation prior to cessation of norepinephrine infusion was associated with an increased risk of hemodynamic instability.

Development of a Coprecepting Model for a Preceptor-in-Training Program for New Practitioners.

Background: Preceptor development is a focus of pharmacy residency programs across the country. Graduation from residency into the role of preceptor can be a challenge, as it is one of many transitions junior practitioners make in their early careers. Literature in recent years has brought attention to the need to establish preceptor development programs that adequately allow newer preceptors to develop their skills in experiential education, for both pharmacy residents and students. Furthermore, many preceptor development programs as implemented are often didactic in nature, and include readings, webinars, and other passive learning regarding the art of precepting. Objective: Given the need to develop a preceptor development program in our service line that met the needs of preceptors-in-training and full preceptors, we offer a description of our preceptor development program in the intensive care unit. Methods: We focused on active development of preceptor skills for multiple layers of resident and student learners. In addition, this model incorporated instructing, modeling, coaching, and facilitating, as the relationship between full preceptor and preceptor-in-training evolved. It also offered the opportunity for real-time feedback and discussion on precepting performance. Conclusions: We describe our coprecepting model as an opportunity that succeeded for us in helping to transition our preceptors-in-training to full preceptors. It met the needs of our department, staff, and patients, and we believe it has the potential to be valuable as a tool extrapolated to the preceptor development programs of other institutions.

Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study.

OBJECTIVES: Although the potential dangers of hyperchloremia from resuscitation fluids continue to emerge, no study to date has considered the contribution of medication diluents to cumulative volume and hyperchloremia. This study compares saline versus dextrose 5% in water as the primary medication diluent and the occurrence of hyperchloremia in critically ill patients. DESIGN: Prospective, open-label, sequential period pilot study. SETTING: Medical ICU of a large academic medical center. PATIENTS: Adult patients admitted to the medical ICU were eligible for inclusion. Patients who were admitted for less than 48 hours, less than 18 years old, pregnant, incarcerated, or who had brain injury were excluded. INTERVENTIONS: Saline as the primary medication diluent for 2 months followed by dextrose 5% in water as the primary medication diluent for 2 months. MEASUREMENTS AND MAIN RESULTS: A total of 426 patients were included, 216 in the saline group and 210 in the dextrose 5% in water group. Medication diluents accounted for 63% of the total IV volume over the observation period. In the saline group, 17.9% developed hyperchloremia compared with 10.5% in the dextrose 5% in water group (p = 0.037), which was statistically significant in multivariable analysis (odds ratio, 0.50; 95% CI, 0.26-0.94; p = 0.031). In the saline group, 34.2% developed acute kidney injury versus 24.5% in the dextrose 5% in water group (p = 0.035); however, this was not statistically significant when adjusting for baseline covariates. No other significant differences in dysnatremias, insulin requirements, glucose control, ICU length of stay, or ICU mortality were observed. CONCLUSIONS: This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.

A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock.

OBJECTIVE: To review and summarize data on angiotensin II (AT-II), approved by the Food and Drug Administration (FDA) in December 2017 to increase blood pressure in adults with septic or other distributive shock. DATA SOURCES: A PubMed/MEDLINE search was conducted using the following terms: (angiotensin ii OR angiotensin 2) AND (shock) from 1966 to February 2018. STUDY SELECTION AND DATA EXTRACTION: A total of 691 citations were reviewed with only relevant clinical data extracted. DATA SYNTHESIS: AT-II is a peptide hormone with a multitude of physiological effects-namely, vasoconstriction of venous and arterial smooth muscle. The priority approval granted by the FDA was secondary to a phase 3 study of patients receiving at least 0.2 µg/kg/min of norepinephrine or equivalent for vasodilatory shock. Compared with placebo, AT-II had a significantly higher rate of response, defined as a mean arterial pressure of 75 mm Hg or an increase of 10 mm Hg. No significant difference was found in death by day 28. CONCLUSIONS: AT-II is a newly available vasoactive agent with a novel mechanism for the treatment of distributive shock. Further research is needed to define its exact role in therapy of shock states, identify patients most likely to benefit, and further study its safety profile in critical illness.

Misdirected Sympathy: The Role of Sympatholysis in Sepsis and Septic Shock.

The spectrum of sepsis and septic shock remains a highly prevalent disease state, carrying a high risk of morbidity and mortality. The sympathetic nervous system (SNS) plays an important role in this initial cascade, enabling the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become of detriment in patients with sepsis has fueled interest in the role and impact of sympatholysis, the selective inhibition of sympathetic tone. The cornerstone of septic shock therapy for decades has been the supplementation of catecholamines and thus potential further perpetuation of this sympathetic dysregulation. Although the theory of sympatholysis circulates around cardiovascular effects and stroke volume optimization, the impact of augmenting the SNS may extend well beyond this, including the impacts on the immune system, inflammatory cascade, and even gene transcription. Presently, the most robust clinical evidence involves the use of the cardioselective ß-blocker esmolol in patients with septic shock with persistent tachycardia secondary to catecholamine use. Evidence is isolated only to animal models with α-agonists. Future evidence stands to elucidate the balance of sympathetic and autonomic tone as well as the potential role of redirecting and maximizing sympathetic activity.

Aggressive Treatment of Life-Threatening Hypophosphatemia During Recovery From Fulminant Hepatic Failure: A Case Report.

Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0.5 mmol/kg/h. The patient required over 400 mmol of total IV and oral phosphorous over the course of 48 hours. An aggressive approach to phosphorous replacement was done safely and effectively. Traditional replacement protocols are not adequate to sustain patients with this degree of hypophosphatemia. This is the first report to utilize a continuous infusion of phosphate with a maximum reported rate (0.5 mmol/kg/h). Our report summarizes a novel and safe approach for clinicians to maximally support these patients through high-dose, continuous infusion phosphorous administration.