Brittany D. Bissell

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.

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 β-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.

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.

12: INSIDIOUS HARM OF MEDICATION DILUENTS AS A CONTRIBUTOR TO CUMULATIVE VOLUME AND HYPERCHLOREMIA

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

1406: ASSESSING THE IMPACT OF ALBUMIN USE ON VASOPRESSOR DURATION AND MORTALITY IN SEPTIC SHOCK

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Albumin use in septic shock is controversial, with large randomized controlled trials generally indicating no difference in outcomes when compared to crystalloids. However, a subgroup analysis from the ALBIOS trial generated the hypothesis that mortality benefit with albumin may be reserved to patients with septic shock, and possibly be associated with a reduction in the duration of vasopressor use. Methods: Retrospective cohort study using ICD9/10 codes to identify septic shock (and confirmed with vasopressor use) in adult patients admitted to the ICU over a 4 year period. Baseline demographics were collected, including SOFA scores, peak lactate, maximum number of vasopressors, and liver disease, among other variables. A patient was classified as receiving albumin if they received 25% albumin while concomitantly receiving vasopressor therapy. A multivariable competing-risk regression model was used to assess time on vasopressor therapy (with death as a competing event) and a multivariable logistic regression model used to assess mortality. Results: Of 2,489 patients screened, 1,168 patients were included. In bivariate analyses, receipt of albumin (n = 493) was generally associated with increased severity of illness, liver disease, worse shock, longer vasopressor duration, worse acute kidney injury, and worse in-hospital mortality compared to no albumin (n = 675). In competing-risk regression adjusting for imbalances in baseline characteristics, use of 25% albumin was not associated with a reduced time on vasopressors (SHR 0.91 95% CI 0.78–1.06; p = 0.24). The receipt of 25% albumin was not associated with hospital mortality in logistic regression modeling (OR 1.13 95% CI 0.83–1.57; p = 0.43). Conclusions: In this retrospective analysis using multivariable modeling and competing-risk analyses, 25% albumin was not associated with a reduction in time on vasopressors or in-hospital mortality in patients with septic shock, however, selection bias may still remain despite attempts to adjust in multivariable modeling.

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.