Incidence and outcomes of acute kidney injury including hepatorenal syndrome in hospitalized patients with cirrhosis in the US.

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis. METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other). RESULTS: A total of 2,063 patients were included (median age 62 [IQR 54-69] years, 38.3% female, median MELD-Na score 26 [19-31]). The most common etiology was prerenal AKI (44.3%), followed by ATN (30.4%) and HRS-AKI (12.1%); 6.0% had other AKI, and 7.2% could not be classified. In our cohort, 8.1% of patients received a liver transplant and 36.5% died by 90 days. The lowest rate of death was observed in patients with prerenal AKI (22.2%; p <0.001), while death rates were higher but not significantly different from each other in those with HRS-AKI and ATN (49.0% vs. 52.7%; p = 0.42). Using prerenal AKI as a reference, the adjusted subdistribution hazard ratio (sHR) for 90-day mortality was higher for HRS-AKI (sHR 2.78; 95% CI 2.18-3.54; p <0.001) and ATN (sHR 2.83; 95% CI 2.36-3.41; p <0.001). In adjusted analysis, higher AKI stage and lack of complete response to treatment were associated with an increased risk of 90-day mortality (p <0.001 for all). CONCLUSION: AKI is a severe complication of cirrhosis. HRS-AKI is uncommon and is associated with similar outcomes to ATN. The etiology of AKI, AKI stage/severity, and non-response to treatment were associated with mortality. Further optimization of vasoconstrictors for HRS-AKI and supportive therapies for ATN are needed. IMPACT AND IMPLICATIONS: Acute kidney injury (AKI) in cirrhosis carries high morbidity, and management is determined by the etiology of injury. However, a large and well-adjudicated multicenter database from US centers that uses updated AKI definitions is lacking. Our findings demonstrate that acute tubular necrosis and hepatorenal syndrome have similar outcomes (∼50% mortality at 90 days), though hepatorenal syndrome is uncommon (12% of all AKI cases). These findings represent practice patterns at US transplant/tertiary centers and can be used as a baseline, presenting the situation prior to the adoption of terlipressin in the US.

Anticoagulation practices for continuous renal replacement therapy: a survey of physicians from the United States.

BACKGROUND: During continuous renal replacement therapy (CRRT), anticoagulants are recommended for patients at low risk of bleeding and not already receiving systemic anticoagulants. Current anticoagulants used in CRRT in the US are systemic heparins or regional citrate. To better understand use of anticoagulants for CRRT in the US, we surveyed nephrologists and critical care medicine (CCM) specialists. METHODS: The survey contained 30 questions. Respondents were board certified and worked in intensive care units of academic medical centers or community hospitals. RESULTS: 150 physicians (70 nephrologists and 80 CCM) completed the survey. Mean number of CRRT machines in use increased ∼30% from the pre-pandemic era to 2022. Unfractionated heparin was the most used anticoagulant (43% of estimated patients) followed by citrate (28%). Respondents reported 29% of patients received no anticoagulant. Risk of hypocalcemia (52%) and citrate safety (42%) were the predominant reasons given for using no anticoagulant instead of citrate in heparin-intolerant patients. 84% said filter clogging was a problem when no anticoagulant was used, and almost 25% said increased transfusions were necessary. Respondents using heparin (n = 131) considered it inexpensive and easily obtainable, although of moderate safety, citing concerns of heparin-induced thrombocytopenia and bleeding. Anticoagulant citrate dextrose solution was the most used citrate. Respondents estimated that 37% of patients receiving citrate develop hypocalcemia and 17% citrate lock. CONCLUSIONS: Given the increased use of CRRT and the lack of approved, safe, and effective anticoagulant choices for CRRT in the US, effective use of current and other anticoagulant options needs to be evaluated.

Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU) Score.

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population. DESIGN: This was a multicenter, observational cohort study. SETTING: Twenty-eight ICUs in the United States. PATIENTS: Adult ICU patients. INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively. MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (ß coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (ß coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (ß coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (ß coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (ß coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (ß coefficient, -0.05; 95% CI, -0.09 to -0.01). CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

Serum IL-17 levels are higher in critically ill patients with AKI and associated with worse outcomes.

BACKGROUND: Interleukin-17 (IL-17) antagonism in rats reduces the severity and progression of AKI. IL-17-producing circulating T helper-17 (TH17) cells is increased in critically ill patients with AKI indicating that this pathway is also activated in humans. We aim to compare serum IL-17A levels in critically ill patients with versus without AKI and to examine their relationship with mortality and major adverse kidney events (MAKE). METHODS: Multicenter, prospective study of ICU patients with AKI stage 2 or 3 and without AKI. Samples were collected at 24-48 h after AKI diagnosis or ICU admission (in those without AKI) [timepoint 1, T1] and 5-7 days later [timepoint 2, T2]. MAKE was defined as the composite of death, dependence on kidney replacement therapy or a reduction in eGFR of ≥ 30% from baseline up to 90 days following hospital discharge. RESULTS: A total of 299 patients were evaluated. Patients in the highest IL-17A tertile (versus lower tertiles) at T1 had higher acuity of illness and comorbidity scores. Patients with AKI had higher levels of IL-17A than those without AKI: T1 1918.6 fg/ml (692.0-5860.9) versus 623.1 fg/ml (331.7-1503.4), p < 0.001; T2 2167.7 fg/ml (839.9-4618.9) versus 1193.5 fg/ml (523.8-2198.7), p = 0.006. Every onefold higher serum IL-17A at T1 was independently associated with increased risk of hospital mortality (aOR 1.35, 95% CI: 1.06-1.73) and MAKE (aOR 1.26, 95% CI: 1.02-1.55). The highest tertile of IL-17A (vs. the lowest tertile) was also independently associated with higher risk of MAKE (aOR 3.03, 95% CI: 1.34-6.87). There was no effect modification of these associations by AKI status. IL-17A levels remained significantly elevated at T2 in patients that died or developed MAKE. CONCLUSIONS: Serum IL-17A levels measured by the time of AKI diagnosis or ICU admission were differentially elevated in critically ill patients with AKI when compared to those without AKI and were independently associated with hospital mortality and MAKE.

Walk the Line-The Importance of Well-Informed Interpretation of QT Prolongation.

Acute care pharmacists play an integral role in identifying drug-drug interactions that may predispose patients to QT prolongation. Although most pharmacists are equipped with a baseline understanding of drug interactions and the risks of QTc prolongation, few understand the limitations of QTc calculation and interpretation. In this commentary, we put forth the notion that at times health care providers, including pharmacists, place an overemphasis on the QTc interval. In the context of using the QTc to guide pharmacotherapy decisions, unintended consequences may include a cascade of effects leading to delays in treatment, suboptimal medication selection, alert fatigue, and overutilization of resources.

Impact of Hyperoncotic Albumin on Duration of Vasopressor Support in Septic Shock: A Propensity Score-Matched Analysis.

BACKGROUND: While albumin has not been shown to reduce mortality in sepsis and septic shock, a tertiary analysis of a large trial suggested that it may reduce the duration of vasopressor use in septic shock. OBJECTIVE: We sought to test if 25% albumin administration was associated with reduced cumulative vasopressor use in septic shock in a real-world setting. METHODS: This was a retrospective, propensity score-matched cohort study of septic shock in which patients receiving albumin were compared with a matched cohort of those not receiving albumin. The primary outcome was days alive and free of vasopressors. RESULTS: The matched cohort included 335 patients who received albumin and 335 who did not. The days alive and free of vasopressors were similar between the albumin and no albumin groups: 17.4 (0-24.8) versus 19.4 (0-25.3); P = 0.160. Similarly, in-hospital mortality was no different between groups (46.9% vs 44.8%; P = 0.587). Receipt of albumin was associated with fewer ventilator-free and intensive care unit (ICU)-free days: 0 (0-19) versus 11 (0-23), P = 0.007, and 0 (0-18) versus 10.6 (0-22.1), P = 0.002, respectively. CONCLUSION AND RELEVANCE: Albumin use in septic shock was not associated with additional days alive and free of vasopressors or in-hospital mortality. The finding of fewer ventilator- and ICU-free days may reflect selection of patients who were critically ill for longer periods of time before or after albumin administration. Additional study is needed to clarify the impact that timing may have on the effectiveness of albumin in septic shock.

Serum renin and major adverse kidney events in critically ill patients: a multicenter prospective study.

BACKGROUND: Preliminary studies have suggested that the renin-angiotensin system is activated in critical illness and associated with mortality and kidney outcomes. We sought to assess in a larger, multicenter study the relationship between serum renin and Major Adverse Kidney Events (MAKE) in intensive care unit (ICU) patients. METHODS: Prospective, multicenter study at two institutions of patients with and without acute kidney injury (AKI). Blood samples were collected for renin measurement a median of 2 days into the index ICU admission and 5-7 days later. The primary outcome was MAKE at hospital discharge, a composite of mortality, kidney replacement therapy, or reduced estimated glomerular filtration rate to ≤ 75% of baseline. RESULTS: Patients in the highest renin tertile were more severely ill overall, including more AKI, vasopressor-dependence, and severity of illness. MAKE were significantly greater in the highest renin tertile compared to the first and second tertiles. In multivariable logistic regression, this initial measurement of renin remained significantly associated with both MAKE as well as the individual component of mortality. The association of renin with MAKE in survivors was not statistically significant. Renin measurements at the second time point were also higher in patients with MAKE. The trajectory of the renin measurements between time 1 and 2 was distinct when comparing death versus survival, but not when comparing MAKE versus those without. CONCLUSIONS: In a broad cohort of critically ill patients, serum renin measured early in the ICU admission is associated with MAKE at discharge, particularly mortality.

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.

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.

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.

Multidisciplinary Prerounding Meeting as a Continuous Quality Improvement Tool: Leveraging to Reduce Continuous Benzodiazepine Use at an Academic Medical Center.

BACKGROUND: Evidence-based medicine often has many barriers to overcome prior to implementation in practice, hence the importance of continuous quality improvement. We report on a brief (≤10 minutes) multidisciplinary meeting prior to rounds to establish a dashboard for continuous quality improvement and studied the success of this meeting on a particular area of focus: continuous infusion benzodiazepine minimization. METHODS: This was a prospective observational study of patients admitted to the medical intensive care unit (MICU) of a large academic medical center over a 4-month period. A morning multidisciplinary prerounding meeting was implemented to report on metrics required to establish a dashboard for MICU care for the previous 24 hours. Fellows and nurse practitioners on respective teams reported on key quality metrics and other important data related to patient census. Continuous benzodiazepines were tracked daily as the number of patients per team who had orders for a continuous benzodiazepine infusion. The aim of this report is to describe the development of the morning multidisciplinary prerounding meeting and its impact on continuous benzodiazepine use, along with associated clinical outcomes. RESULTS: The median number of patients prescribed a continuous benzodiazepine daily decreased over this time period and demonstrated a sustained reduction at 1 year. Furthermore, sedation scores improved, corresponding to a reduction in median duration of mechanical ventilation. The effectiveness of this intervention was mapped post hoc to conceptual models used in implementation science. CONCLUSIONS: A brief multidisciplinary meeting to review select data points prior to morning rounds establishes mechanisms for continuous quality improvement and may serve as a mediating factor for successful implementation when initiating and monitoring practice change in the ICU.

Acute Hepatotoxicity After High-Dose Cytarabine for the Treatment of Relapsed Acute Myeloid Leukemia: A Case Report.

Purpose: Cytarabine is considered the standard of care for induction therapy in patients with acute myeloid leukemia (AML) who are preparing for bone marrow transplant. Summary: We report a case of a 72-year-old female presenting to the intensive care unit with hepatic failure after high-dose cytarabine (HiDAC) for the treatment of relapsed AML. The patient's liver function tests (LFTs) were elevated acutely, with a mildly elevated bilirubin and a normal alkaline phosphatase. HiDAC was discontinued but her LFTs remained high for 9 days post discontinuation, and the patient eventually expired due to sepsis and multiple organ failure. We estimated the probability of the hepatotoxicity observed with HiDAC as probable based on a score of 5 on the Naranjo scale. Conclusion: Clinicians should be aware of the potential hepatotoxicity associated with HiDAC for patients with AML, specifically in the elderly population.

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.

Effect of Thiamine Administration on Lactate Clearance and Mortality in Patients With Septic Shock.

OBJECTIVES: Mounting evidence has shown that critically ill patients are commonly thiamine deficient. We sought to test the hypothesis that critically ill patients with septic shock exposed to thiamine would demonstrate improved lactate clearance and more favorable clinical outcomes compared with those not receiving thiamine. DESIGN: Retrospective, single-center, matched cohort study. SETTING: Tertiary care academic medical center. PATIENTS: Adult patients admitted with an International Classification of Diseases, 9th Edition, or International Classification of Diseases, 10th Edition, diagnosis code of septic shock to either the medicine or surgery ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients who received IV thiamine supplementation within 24 hours of hospital admission were identified and compared with a matched cohort of patients not receiving thiamine. The primary objective was to determine if thiamine administration was associated with a reduced time to lactate clearance in septic shock. Secondary outcomes included 28-day mortality, acute kidney injury, and need for renal replacement therapy, and vasopressor and mechanical ventilation-free days. Two-thousand two-hundred seventy-two patients were screened, of whom 1,049 were eligible. The study consisted of 123 thiamine-treated patients matched with 246 patients who did not receive thiamine. Based on the Fine-Gray survival model, treatment with thiamine was associated with an improved likelihood of lactate clearance (subdistribution hazard ratio, 1.307; 95% CI, 1.002-1.704). Thiamine administration was also associated with a reduction in 28-day mortality (hazard ratio, 0.666; 95% CI, 0.490-0.905). There were no differences in any secondary outcomes. CONCLUSIONS: Thiamine administration within 24 hours of admission in patients presenting with septic shock was associated with improved lactate clearance and a reduction in 28-day mortality compared with matched controls.

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.

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.

Comparison of High-Dose Versus Standard Dose Oseltamivir in Critically Ill Patients With Influenza.

BACKGROUND: Limited data support high-dose oseltamivir in critically ill patients with influenza. In several recent influenza seasons, there were oseltamivir drug shortages. METHODS: This was a retrospective cohort analysis of 57 patients admitted to the intensive care unit (ICU) with confirmed influenza. Patients receiving high-dose oseltamivir were compared to those receiving standard dosing. RESULTS: When adjusted for clinically relevant predictors of disease severity, including age, duration of therapy, Acute Physiology and Chronic Health Evaluation II score, and receipt of extracorporeal membrane oxygenation, there was no difference in the duration of mechanical ventilation, oxygenation, ICU length of stay, or hospital length of stay between the high-dose and standard dose groups. CONCLUSIONS: As compared to the standard doses of oseltamivir, higher-dose (ie, double dose) oseltamivir was not associated with improvement in any clinical outcomes. Using higher doses empirically on all patients during influenza season may exacerbate local drug shortages.

Heparin induced thrombocytopenia with mechanical circulatory support devices: review of the literature and management considerations.

Whether for temporary or long term use, mechanical circulatory support (MCS) has seen increased utilization and interest over the past several years. Even though these devices innately cause thrombocytopenia, co-administration of heparin anticoagulation carries the risk for heparin-induced thrombocytopenia (HIT). This poses challenges for practitioners as very few studies provide guidance for the management of this condition, particularly in this population. This has led to a wide spectrum of treatment protocols within current practice. This review was developed to bring together available literature on the management of HIT in patients with MCS along with practical experience and clinical opinion in order to help guide the management of these patients.

Unpeeling the Evidence for the Banana Bag: Evidence-Based Recommendations for the Management of Alcohol-Associated Vitamin and Electrolyte Deficiencies in the ICU.

OBJECTIVE: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a "banana bag" as a reflexive standard of therapy. The difficulty of diagnosing Wernicke's encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence. DATA SOURCE: MEDLINE/PubMed (1966 to June 2015) database search, the Cochrane Database of Systematic Reviews, and manual selection of bibliographies from selected articles. STUDY SELECTION AND DATA EXTRACTION: Articles relevant to Wernicke's encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected. Articles were narratively synthesized for this review. DATA SYNTHESIS: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation as for prescribing thiamine in this setting. There is no available evidence supporting the prescription of a multivitamin. CONCLUSIONS: Based on the published literature, for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke's encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200-500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4-5 g for most adult patients), and 400-1,000 µg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.