Nephrotoxic Risk Associated With Combination Therapy of Vancomycin and Piperacillin-Tazobactam in Critically Ill Patients With Chronic Kidney Disease.

Background: The combination of vancomycin and piperacillin-tazobactam (VPT) has been associated with acute kidney injury (AKI) in hospitalized patients when compared to similar combinations. Additional studies examining this nephrotoxic risk in critically ill patients have not consistently demonstrated the aforementioned association. Furthermore, patients with baseline renal dysfunction have been excluded from almost all of these studies, creating a need to examine the risk in this patient population. Methods: This was a retrospective cohort analysis of critically ill adults with baseline chronic kidney disease (CKD) who received vancomycin plus an anti-pseudomonal beta-lactam at Emory University Hospital. The primary outcome was incidence of AKI. Secondary outcomes included stage of AKI, time to development of AKI, time to return to baseline renal function, new requirement for renal replacement therapy, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 109 patients were included. There was no difference observed in the primary outcome between the VPT (50%) and comparator (58%) group (P = .4), stage 2 or 3 AKI (15.9% vs 6%; P = .98), time to AKI development (1.7 vs 2 days; P = .5), time to return to baseline renal function (4 vs 3 days; P = .2), new requirement for RRT (4.5% vs 1.5%; P = .3), ICU length of stay (7.3 vs 7.4 days; P = .9), hospital length of stay (19.3 vs 20.1 days; P = .87), or in-hospital mortality (15.9% vs 10.8%; P = .4). A significant difference was observed in the duration of antibiotic exposure (3.32 vs 2.62 days; P = .045 days). Conclusion: VPT was not associated with an increased risk of AKI or adverse renal outcomes. Our findings suggest that the use of this antibiotic combination should not be avoided in this patient population. More robust prospective studies are warranted to confirm these findings.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations

To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute liver failure (ALF) or acute on chronic liver failure (ACLF) in the ICU. DESIGN: The guideline panel comprised 27 members with expertise in aspects of care of the critically ill patient with liver failure or methodology. We adhered to the Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. INTERVENTIONS: In part 2 of this guideline, the panel was divided into four subgroups: neurology, peri-transplant, infectious diseases, and gastrointestinal groups. We developed and selected Population, Intervention, Comparison, and Outcomes (PICO) questions according to importance to patients and practicing clinicians. For each PICO question, we conducted a systematic review and meta-analysis where applicable. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: We report 28 recommendations (from 31 PICO questions) on the management ALF and ACLF in the ICU. Overall, five were strong recommendations, 21 were conditional recommendations, two were best-practice statements, and we were unable to issue a recommendation for five questions due to insufficient evidence. CONCLUSIONS: Multidisciplinary, international experts formulated evidence-based recommendations for the management ALF and ACLF patients in the ICU, acknowledging that most recommendations were based on low quality and indirect evidence.

A Case of "Cryptammonia": Disseminated Cryptococcal Infection Generating Profound Hyperammonemia in a Liver Transplant Recipient.

Mycoplasma and Ureaplasma infections have been described as a cause of hyperammonemia syndrome leading to devastating neurological injury in the post-transplant period, most commonly in lung transplant recipients. The occurrence of significant hyperammonemia caused by other urease-producing organisms remains unclear. We describe a case of disseminated cryptococcosis presenting with profound hyperammonemia in a 55-year-old orthotopic liver transplant recipient. Through a process of elimination, other potential causes for hyperammonemia were excluded revealing a probable association between hyperammonemia and disseminated cryptococcosis.

Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Cardiovascular, Endocrine, Hematologic, Pulmonary, and Renal Considerations.

OBJECTIVES: To develop evidence-based recommendations for clinicians caring for adults with acute or acute on chronic liver failure in the ICU. DESIGN: The guideline panel comprised 29 members with expertise in aspects of care of the critically ill patient with liver failure and/or methodology. The Society of Critical Care Medicine standard operating procedures manual and conflict-of-interest policy were followed throughout. Teleconferences and electronic-based discussion among the panel, as well as within subgroups, served as an integral part of the guideline development. SETTING: The panel was divided into nine subgroups: cardiovascular, hematology, pulmonary, renal, endocrine and nutrition, gastrointestinal, infection, perioperative, and neurology. INTERVENTIONS: We developed and selected population, intervention, comparison, and outcomes questions according to importance to patients and practicing clinicians. For each population, intervention, comparison, and outcomes question, we conducted a systematic review aiming to identify the best available evidence, statistically summarized the evidence whenever applicable, and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used the evidence to decision framework to facilitate recommendations formulation as strong or conditional. We followed strict criteria to formulate best practice statements. MEASUREMENTS AND MAIN RESULTS: In this article, we report 29 recommendations (from 30 population, intervention, comparison, and outcomes questions) on the management acute or acute on chronic liver failure in the ICU, related to five groups (cardiovascular, hematology, pulmonary, renal, and endocrine). Overall, six were strong recommendations, 19 were conditional recommendations, four were best-practice statements, and in two instances, the panel did not issue a recommendation due to insufficient evidence. CONCLUSIONS: Multidisciplinary international experts were able to formulate evidence-based recommendations for the management acute or acute on chronic liver failure in the ICU, acknowledging that most recommendations were based on low-quality indirect evidence.

Sugammadex for Neuromuscular Blockade Reversal.

Postoperative residual neuromuscular blockade is associated with an increased risk of respiratory insufficiency, aspiration, and potential pulmonary complications. The standard of care for reversal of residual block centers on anticholinesterases such as neostigmine. However, these medications provide inconsistent or inadequate effect while being associated with potentially severe adverse effects. Sugammadex, a modified γ-cyclodextrine compound, is a recently approved agent for the reversal of blockade with aminosterodial neuromuscular blockers. Randomized controlled trials, in addition to a meta-analysis and a systematic review, have published results indicating faster and more consistent reversal of blockade while leading to fewer adverse events.

Pharmacologic Issues in Liver Disease.

This article describes key concepts for drug dosing considerations in liver disease. Included in this article is a review of pharmacokinetic changes that are known to occur in patients with liver disease that can aide in drug dosing. Although limited, the currently available pharmacokinetic data for medications that are commonly used in the critical care setting are also included.

Prescribing patterns of hydrocortisone in septic shock: a single-center experience of how surviving sepsis guidelines are interpreted and translated into bedside practice.

OBJECTIVES: The Surviving Sepsis Campaign suggests giving hydrocortisone to septic patients only if their "blood pressure is poorly responsive to fluid resuscitation and vasopressor therapy." Because the definition of "poorly responsive" is not provided, the purpose of this study was to identify prescribing triggers for hydrocortisone in septic shock. DESIGN: Retrospective chart review of patients with septic shock over 17 months, who received hydrocortisone, followed by a survey of all intensivists who attended in the study ICUs to determine whether provider attitudes matched clinical practice. SETTING: Eight ICUs in an academic hospital and a hybrid academic/community hospital. PATIENTS: A total of 155 patients with septic shock in whom vasopressors were initiated and hydrocortisone was prescribed. MEASUREMENTS AND MAIN RESULTS: Ninety-nine patients (64%) were already receiving two vasopressors before hydrocortisone was prescribed. An additional 22 patients were on a single high-dose vasopressor prior to corticosteroid initiation. Of patients who survived to have their hydrocortisone dose changed, 57% had their corticosteroids tapered, whereas 43% were abruptly discontinued. Seventy-six percent of patients were no longer on vasopressors when the first dosing change was made. Twenty-seven out of 36 intensivists (75%) completed the survey. The majority (72%) defined "poorly responsive to vasopressors" as the presence of two vasopressors, and 70% stated that they required patients to be off vasopressors prior to altering the corticosteroid dose. CONCLUSIONS: Significant variability exists when corticosteroids are prescribed for septic shock, with the most common interpretation in our institution of "poorly responsive to fluid resuscitation and vasopressor therapy" being the presence of two vasopressors. The method and timing of corticosteroid discontinuation also differed among providers. Self-described prescribing patterns from intensivists closely matched their actual behavior, suggesting variability is due to differing interpretations of the guidelines themselves, rather than a deficit in knowledge translation.