Singbartl, Kai

AbstractBackgroundVeno‐arterial extracorporeal life support (V‐A ECLS) has become a cornerstone in the management of critical cardiogenic shock, but it can also precipitate organ injury, e.g., acute kidney injury (AKI). Available studies highlight the effect of non‐cardiac organ injury on patient outcomes. Only very little is known about the impact of non‐cardiac organ recovery on patient survival. AKI occurs frequently during cardiogenic shock and carries a poor prognosis. We have developed descriptive models to hypothesize on the role of AKI severity versus that of recovery of renal function for patient survival.MethodsRetrospective, observational study including 175 patients who were successfully decannulated from V‐A ECLS. We assessed AKI severity using the “Kidney Disease: Improving Global Outcomes” (KDIGO) criteria. We defined recovered or preserved renal function (RPRF) prior to decannulation from V‐A ECLS as 0 (AKI with no improvement) or 1 (no AKI or AKI with improvement). We classified patient outcomes as alive or dead at hospital discharge.Results78% (n = 138) of all patients survived hospital discharge of which 38% (n = 67) never developed AKI. After adjusting for shock severity and non‐renal organ injury, RPRF emerged as an independent predictor of survival in both the overall cohort [OR (95% CI) – 4.11 (1.72–9.79)] and the AKI‐only sub‐cohort [OR (95% CI) – 5.18 (1.8–14.92)]. Neither maximum KDIGO stage nor KDIGO stage at the end of V‐A ECLS was independently associated with survival.ConclusionsOur model identifies RPRF, but not AKI severity, as an independent predictor of hospital survival in patients undergoing V‐A ECLS for cardiogenic shock. We hypothesize that recovered or preserved non‐cardiac organ function during V‐A ECLS is crucial for patient survival.

Abstract Rationale Urinary TIMP-2 (tissue inhibitor of metalloproteinases-2) and IGFBP7 (insulin-like growth factor–binding protein 7) can predict acute kidney injury (AKI) in patients with sepsis. Objectives To address critical questions about whether biomarkers can inform the response to treatment and whether they might be used to guide therapy, as most sepsis patients present with AKI. Methods We measured [TIMP-2] · [IGFBP7] before and after a 6-hour resuscitation in 688 patients with septic shock enrolled in the ProCESS (Protocol-based Care for Early Septic Shock) trial. Our primary endpoint was stage 3 AKI, renal replacement therapy, or death within 7 days. Measurements and Main Results: The endpoint was reached in 113 patients (16.4%). In patients with negative [TIMP-2] · [IGFBP7] at baseline, those who became positive (>0.3 U) after resuscitation had three-times higher risk compared with those who remained negative (21.8% vs. 8.5%; P = 0.01; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.31–6.87). Conversely, compared with patients with a positive biomarker at baseline that were still positive at Hour 6, risk was reduced for patients who became negative (23.8% vs. 9.8%; P = 0.01; OR, 2.15; 95% CI, 1.17–3.95). A positive [TIMP-2] · [IGFBP7] after resuscitation was associated with worse outcomes in both patients with and without AKI at that time point. The clinical response to resuscitation, as judged by the Acute Physiology and Chronic Health Evaluation II score, was weakly predictive of the endpoint (area under the curve, 0.68; 95% CI, 0.62–0.73) and improved with addition of [TIMP-2] · [IGFBP7] (0.72; 95% CI, 0.66–0.77; P = 0.03). Different resuscitation protocols did not alter biomarker trajectories, nor did they alter outcomes in biomarker-positive or biomarker-negative patients. However, biomarker trajectories were associated with outcomes. Conclusions Changes in urinary [TIMP-2] · [IGFBP7] after initial fluid resuscitation identify patients with sepsis who have differing risk for progression of AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 00510835).

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.

Abstract Peripheral veno‐arterial extracorporeal membrane oxygenation (pVA‐ECMO) has gained increasing value in the management of patients with critical cardiogenic shock (cCS), allowing time for myocardial recovery. Failure of myocardial recovery has life‐altering consequences: transition to durable mechanical circulatory support (dMCS), urgent heart transplantation, or withdrawal of support. Clinical factors controlling myocardial recovery under these circumstances remain largely unknown. Using a retrospective cohort, we developed a model for early prediction of transition to dMCS in patients undergoing pVA‐ECMO for cCS. To promote myocardial recovery, our clinical management centered around left ventricular pressure unloading, that is, targeting pulmonary capillary wedge pressures (PCWP) ≤18 mm Hg. We collected demographic data, laboratory findings, inotrope use, and two‐dimensional transthoracic echocardiography measurements, all limited to the first 72h of pVA‐ECMO (D1‐3). Out of 70 patients who were alive after pVA‐ECMO, 27 patients underwent implantation of dMCS. There was no significant difference in survival to hospital discharge between patients with or without transition to dMCS. Ejection fraction D1‐3 (per 10% increase, OR 0.37 [0.17‐0.79]) and amount of inotropic support D1‐3 (OR 4.77 [1.6‐14.18]) but neither myocardial wall tension nor PCWP emerged as significant predictors of transition to dMCS. Optimism‐corrected c‐index (0.90 [0.89‐0.90]) revealed an excellent discriminative ability of our model. In summary, our model for early prediction of transition to dMCS in patients with cCS undergoing pVA‐ECMO identifies indicators of inotropic state as relevant factors. Absence of markers for myocardial oxygen consumption or left ventricular pressure loading allows us to hypothesize sufficient cardiac unloading in our cohort with PCWP‐targeted management.

AbstractThe liver and kidney are key organs of metabolic homeostasis in the body and display complex interactions. Liver diseases often have direct and immediate effects on renal physiology and function. Conversely, acute kidney injury (AKI) is a common problem in patients with both acute and chronic liver diseases. AKI in patients with acute liver failure is usually multifactorial and involves insults similar to those seen in the general AKI population. Liver cirrhosis affects and is directly affected by aberrations in systemic and renal hemodynamics, inflammatory response, renal handling of sodium and free water excretion, and additional nonvasomotor mechanisms. Subsequent problems, for example, worsening ascites, hyponatremia, and AKI, often complicate management of patients with chronic progressive liver disease and add to their morbidity and mortality. Thus, AKI must be carefully defined and diagnosed in patients with liver disease. The kidney also plays a pivotal role in balancing acid–base disturbances resulting from advanced liver disease, making AKI in the setting of end-stage liver disease very difficult to manage clinically. While renal dysfunction in these patients often resolves following orthotopic liver transplant, dialysis may be required as a bridge to transplantation to mitigate the metabolic disarray found in these critically ill patients.

AbstractVeno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) provides mechanical circulatory support for patients with advanced cardiogenic shock, facilitating myocardial recovery and limiting multi‐organ failure. In patients with severely limited left ventricular ejection, peripheral VA‐ECMO can further increase left ventricular and left atrial pressures (LAP). Failure to decompress the left heart under these circumstances can result in pulmonary edema and upper body hypoxemia, that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in these situations. However, the effects of atrial septostomy on upper body oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult VA‐ECMO patients between January 2011 and June 2016 who also underwent atrial septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), PaO2/FiO2 ratios (blood samples from right radial artery), intrathoracic volume status, and resolution of pulmonary edema before and up to 48 h after septostomy. There were no procedure‐related complications. Thirty‐day survival was 44%. LAP/PCWP decreased by approximately 40% immediately following septostomy and remained so for at least 24 h. PaO2/FiO2 ratios significantly increased from 0.49 (0.38–2.12) before to 5.35 (3.01–7.69) immediately after septostomy and continued so for 24 h, 6.6 (4.49–10.93). Radiographic measurements also indicated a significant improvement in thoracic intravascular volume status after atrial septostomy. Atrial septostomy reduces LAP and improves upper body oxygenation and intrathoracic vascular volume status in patients developing severe refractory pulmonary edema while undergoing peripheral VA‐ECMO. Atrial septostomy therefore appears safe and suitable to reduce the risk of upper body ischemia under these circumstances.