Georg F. Lehner

Oliguria and Biomarkers of Acute Kidney Injury: Star Struck Lovers or Strangers in the Night?

Oliguria is a common phenomenon that is found in hospitalized patients . Although a rapid reduction in urine excretion rate may reflect a precipitous fall in the glomerular filtration rate, in many cases it may not. Given the common physiological finding of oliguria, we explore the relationship between the functional biomarker of renal injury (oliguria) with the increasing number of markers of renal injury to see if this combination may aid in risk stratification.

Characterization of Microvesicles in Septic Shock Using High-Sensitivity Flow Cytometry.

Purpose: Endothelial pathology is considered to play a key role in septic shock. Since endothelial-derived microvesicles (MV) are elevated in various diseases associated with endothelial pathology, they are considered surrogate markers of the endothelial state. By analyzing the signature of circulating MV with high-sensitivity flow cytometry (hsFC), we wanted to test the hypothesis whether endothelial-derived MV are increased in septic shock. Methods: MV in blood from healthy volunteers and patients with septic shock treated in a medical intensive care unit were quantified by hsFC, which has an improved detection limit of approximately 0.3 &mgr;m. Results: Patients with septic shock (n = 30) showed 3-fold higher levels of CD31+/CD41− MV (58.5 (26.4–101.2) [median (25th–75th percentile)] vs. 19.5 (12.8–25.4) MV/&mgr;L; P <0.001) compared with healthy volunteers (n = 18). Absolute counts of CD144+, CD62E+, and CD106+ MV, specific for endothelial-derived MV, were low in all groups. The number of CD31+/CD41− MV correlated significantly with leukocyte count (rs = 0.64; P <0.001). Platelet-derived CD41+ MV were significantly elevated in the group dying within 48 h after inclusion (639.1 (321.3–969.7) vs. 221.5 (119.5–456.9) MV/&mgr;L; P = 0.037). Patients dying within 48 h had also significantly higher levels of CD31+/CD41−/AnnexinV− MV (51.9 (24.9–259.8) vs. 18.9 (9.7–31) MV/&mgr;L; P = 0.028). Conclusions: Despite an improved detection limit for MV by using hsFC, counts of endothelial-specific MV are unexpectedly low in patients with septic shock. Increased amounts of CD41+ and CD31+/CD41−/AnnexinV− MV indicate release by activated platelets and possibly leukocytes correlating with unfavorable outcome.

Outcome prediction and temperature dependency of MR-proANP and Copeptin in comatose resuscitated patients.

OBJECTIVE To evaluate the prognostic potential of serum C-terminal provasopressin (CT-proAVP or Copeptin) and midregional pro-A-type natriuretic peptide (MR-proANP) to predict neurological outcome following resuscitation from cardiac arrest. METHODS In this prospective observational study, we employed novel ultra sensitive immunoassay technology to examine serial serum samples from 134 cardiac arrest patients. Patients were either allocated to mild therapeutic hypothermia using an endovascular device or normothermia. Serial blood samples were obtained from resuscitated cardiac arrest survivors during their first 7 days in an intensive care unit, and serum Copeptin and MR-proANP were measured. Cerebral function assessments were made using cerebral performance categorization (CPC) at discharge from hospital. Copeptin and MR-proANP data were analyzed using dichotomized CPC scores (1-2 versus 3-5). RESULTS Sixty-nine patients (51%) had a poor outcome (CPC 3-5) at hospital discharge. MR-proANP and Copeptin peaked on day 1 (i.e. 0-24h) with the medians being 249.3pmol/L and 77.2pmol/L, respectively. In the first 48h maximum levels of MR-proANP and Copeptin showed an AUC in the ROC of 0.743 (95% CI: 0.658-0.828) and 0.677 (95% CI: 0.583-0.771). Binary logistic regression revealed MR-proANP and Copeptin within 48h after ROSC being significantly associated with functional outcome (p<0.05). Copeptin within 48h was also associated with outcome in the hypothermia group (p<0.05). CONCLUSION Systemic levels of MR-proANP and Copeptin peak early in cardiac arrest patients in the 48h post-resuscitation period. MR-proANP and Copeptin were highly predictive for poor outcome in comatose resuscitated patients.

Repeated premature hemofilter clotting during regional citrate anticoagulation as indicator of heparin induced thrombocytopenia.

Purpose: Early clinical signs of heparin induced thrombocytopenia (HIT) are nonspecific and include a sudden drop in the number of platelets as well as formation of arterial and venous thromboses. Regional citrate anticoagulation (RCA) is increasingly used as a very effective modality to prevent filter clotting during renal replacement therapy (RRT). We report the first case where repeated premature filter clotting despite RCA indicated a manifestation of HIT. Materials and Methods: A 71-year old woman admitted to the ICU for a compartment syndrome of the leg developed septic shock with acute kidney injury requiring continuous veno-venous hemodialysis (CVVHD). Because of unexpected and repeated premature filter clotting during CVVHD using RCA, HIT was suspected. Results: The diagnosis of HIT was confirmed by the presence of IgG antibodies against heparin and platelet factor (PF) 4 complexes and six points in the 4T score. Discontinuation of heparin administration and initiation of systemic anticoagulation with danaparoid sodium resulted in the normalization of platelet count and hemofilter lifetime. Conclusion: RCA does not seem to be sufficient to prevent hemofilter clotting during HIT. Thus, in case of repeated premature filter clotting despite RCA, one should suspect HIT and prompt diagnostic workup as well as a switch to alternative anticoagulation. i 2014 S. Karger AG, Basel

Insufficient performance of serum cystatin C as a biomarker for acute kidney injury of postrenal etiology.

Dear Editor, Royakkers et al. [1] recently reported that serum and urinary cystatin C appear to be poor biomarkers for the early detection of acute kidney injury (AKI) in critically ill patients and cannot predict the need for renal replacement therapy (RRT). In this context we present the case of a 65-year-old man with AKI showing nearly normal serum cystatin C levels despite excessive creatinine levels due to AKI. The patient, who had a history of type II diabetes, hypertension, and chronic kidney disease (CKD, stage 3), was admitted to the hospital with severe shortness of breath and bilateral pleural effusions. The right kidney had been removed because of tuberculosis several years before. During the 2 weeks before admission the patient had noticed gross hematuria. The initial CT scan revealed moderate hydronephrosis as well as a minor infiltration in the right middle lobe of the lung. The patient’s condition deteriorated rapidly, requiring intubation for acute respiratory failure as well as vasopressor therapy and volume resuscitation for vasodilatory shock. Inflammatory markers were significantly increased [C-reactive protein (CRP) 1.22 mg/dl, normal 0–0.7; procalcitonin (PCT) 6 lg/l, normal 0–0.5; white blood cell (WBC) 16.7 G/l). The sepsis-related organ failure assessment (SOFA) and acute physiology, age, chronic health evaluation (APACHE) II scores at admission were 15 and 43, respectively. Placement of a urinary catheter resulted in 200 ml of urine with gross hematuria and leukocytes. A diagnosis of urosepsis due to postrenal obstruction was made. Because of persistent oliguria, acidosis (pH 6.9), and hyperkalemia (potassium 7.44 mmol/l) and severe azotemia (creatinine 17.23 mg/dl, normal 0.67–1.17; urea 298.4 mg/dl, normal 18–55) continuous venovenous hemodialysis (CVVHD) was initiated using regional citrate anticoagulation (MultiFiltrate Ci-Ca, Fresenius Medical Care, Bad Homburg, Germany) with an Ultraflux AV 1000 S filter. Blood flow was 100 ml/min and dialysate rate 2,000 ml/h. Despite pronounced azotemia serum cystatin C was only slightly elevated (1.43 mg/l, normal range 0.47–1.09). Within 12 h of CVVHD serum creatinine decreased to 7.68 mg/dl and serum cystatin C to 1.14 mg/l (Fig. 1). During the following days of treatment serum creatinine and urea constantly declined, whereas serum cystatin C increased for another 7 days until the maximum level of 2.33 mg/l was reached. After stabilization of the patient a diagnostic urethrocystoscopy was performed and revealed a multilocalized, infiltrating carcinoma of the bladder obstructing the urethra—presumably the cause of postrenal failure and urosepsis. After 15 days CVVHD was discontinued and the patient was switched to intermittent hemodialysis. Cystatin C is a 13.3-kDa protein that is produced at a constant rate by nucleated cells. It is freely filtered by glomeruli, reabsorbed, and almost completely metabolized by the proximal renal tubule. Serum cystatin C has been shown to respond promptly to early reductions of (glomerular filtration rate) GFR in CKD [2]. In cases of a sudden drop of GFR characteristic of AKI, serum cystatin C was found to increase similarly to creatinine but more rapidly [3]. In discrepancy to this concept our patient with underlying CKD had only slightly elevated serum cystatin C levels in the presence of severe azotemia due to postrenal obstruction on admission. A likely explanation for this finding may be that during the acute phase of obstructive AKI some glomerular filtration is still

From persistence to palliation: limiting active treatment in the ICU.

Purpose of reviewEnd-of-life care and communication deficits are important sources of conflicts within ICU teams and with patients or families. This narrative review describes recent studies on how to improve palliative care and surrogate decision-making in ICUs and compares the results with previously published literature on this topic. Recent findingsAwareness and use of end-of-life recommendations is still low. Education about end-of-life is beneficial for end-of-life decisions. Residency and nurses training programmes start to integrate palliative care education in critical care. Integration of palliative care consults is recommended and probably cost-effective. Projects that promote direct contact of care team members with patients/families may be more likely to improve care than educational interventions for caregivers only. The familys response to critical illness includes adverse psychological outcome (‘postintensive care syndrome–family’). Information brochures and structured communication protocols are likely to improve engagement of family members in surrogate decision-making; however, validation of outcome effects of their use is needed. SummaryOptimizing palliative care and communication skills is the current challenge in ICU end-of-life care. Intervention strategies should be interdisciplinary, multiprofessional and family-centred in order to quickly reach these goals.

Coagulation Disorders in Subjects Undergoing Pump-Driven Veno-Venous Ecco2-R For Severe Acute Hypercapnic Respiratory Failure - a Single Center Experience

Recent evidence suggests low-flow extracorporeal CO2 removal (ECCO2-R) systems as safe and promising adjunctive therapy to avoid endotracheal intubation and the related negative consequences in subjects with severe hypercapnic respiratory failure [1]. in high-flow extracorporeal membrane oxygenation systems heterogeneous coagulation disorders are a well-known complication. However, to date there is little evidence for the influence of pump-driven low-flow veno-venous ECCO2-R on the coagulation system.

Effects of mild therapeutic hypothermia on acute kidney injury after cardiopulmonary resuscitation

About the effect of mild therapeutic hypothermia on renal function after cardiopulmonary resuscitation little data exists. From animal and human studies it is known that renal function might be impaired, which is not reflected by serum creatinine levels if creatinine production is reduced.