ICG-liver test versus new biomarkers as prognostic markers for prolonged length of stay in critically ill patients - a prospective study of accuracy for prediction of length of stay in the ICU.

BACKGROUND: Prognostic abilities of medical parameters, which are scoring systems, measurements and biomarkers, are important for stratifying critically ill patients. Indocyanine green plasma disappearance (ICG-PDR) is an established clinical tool for the assessment of liver perfusion and function. Copeptin, MR-proANP and pro-ADM are biomarkers whose prognostic value is still unclear. The goal of this prospective study was to evaluate ICG-PDR, copeptin, MR-proANP and pro-ADM to predict prolonged length of stay (pLOS) in the ICU. METHODS: This study was conducted as a prospective single center study including 110 consecutively admitted ICU patients. Primary endpoint was prolonged length of stay (pLOS) in the ICU, defined as more than three days of stay there. RESULTS: ROC analysis showed an AUC of 0.73 for ICG-PDR, 0.70 for SAPS II, 0.65 for MR-proANP, 0.64 for pro-ADM and 0.54 for copeptin for pLOS in the ICU. CONCLUSIONS: The prediction of pLOS in the ICU might be better by means of ICG-PDR than with the new biomarkers copeptin, MR-proANP or pro-ADM. Nevertheless, there is more need for research to evaluate whether ICG-PDR is an overall prognostic marker for pLOS. TRIAL REGISTRATION: (ClinicalTrials.gov number, NCT01126554).

Prolonged continuous intravenous infusion of the dipeptide L-alanine- L-glutamine significantly increases plasma glutamine and alanine without elevating brain glutamate in patients with severe traumatic brain injury.

INTRODUCTION: Low plasma glutamine levels are associated with worse clinical outcome. Intravenous glutamine infusion dose- dependently increases plasma glutamine levels, thereby correcting hypoglutaminemia. Glutamine may be transformed to glutamate which might limit its application at a higher dose in patients with severe traumatic brain injury (TBI). To date, the optimal glutamine dose required to normalize plasma glutamine levels without increasing plasma and cerebral glutamate has not yet been defined. METHODS: Changes in plasma and cerebral glutamine, alanine, and glutamate as well as indirect signs of metabolic impairment reflected by increased intracranial pressure (ICP), lactate, lactate-to-pyruvate ratio, electroencephalogram (EEG) activity were determined before, during, and after continuous intravenous infusion of 0.75 g L-alanine-L-glutamine which was given either for 24 hours (group 1, n = 6) or 5 days (group 2, n = 6) in addition to regular enteral nutrition. Lab values including nitrogen balance, urea and ammonia were determined daily. RESULTS: Continuous L-alanine-L-glutamine infusion significantly increased plasma and cerebral glutamine as well as alanine levels, being mostly sustained during the 5 day infusion phase (plasma glutamine: from 295 ± 62 to 500 ± 145 µmol/ l; brain glutamine: from 183 ± 188 to 549 ± 120 µmol/ l; plasma alanine: from 327 ± 91 to 622 ± 182 µmol/ l; brain alanine: from 48 ± 55 to 89 ± 129 µmol/ l; p < 0.05, ANOVA, post hoc Dunn's test). CONCLUSIONS: High dose L-alanine-L-glutamine infusion (0.75 g/ kg/ d up to 5 days) increased plasma and brain glutamine and alanine levels. This was not associated with elevated glutamate or signs of potential glutamate-mediated cerebral injury. The increased nitrogen load should be considered in patients with renal and hepatic dysfunction. TRIAL REGISTRATION: Clinicaltrials.gov NCT02130674. Registered 5 April 2014.

Early fluid resuscitation with hydroxyethyl starch 130/0.4 (6%) in severe burn injury: a randomized, controlled, double-blind clinical trial.

INTRODUCTION: There are limited data on the efficacy of early fluid resuscitation with third-generation hydroxyethyl starch (HES 130) in burn injury. Adverse effects of HES on survival and organ function have been reported. METHODS: In this randomized, controlled, double-blind trial, 48 patients with severe burn injury were assigned to receive either lactated Ringer's solution plus 6% HES 130/0.4 in a ratio of 2:1 or lactated Ringer's solution with no colloid supplement for the first 72 hours. Primary outcome parameter was the group difference of administered total fluid from intensive care unit (ICU) admission up to day 3. Secondary outcomes included kidney and lung injury and failure, length of stay, and mortality. RESULTS: Three-day totals of administered resuscitation fluid (medians) were 21,190 mL in the lactated Ringer's group and 19,535 mL in the HES group (HES: -1,213 mL; P = 0.39). Creatinine levels from day 1 to 3 (HES: +0.4 µmol/L; 95% confidence interval (CI) -18.7 to 19.5; P = 0.97) and urinary outputs from day 1 to 3 (HES: -58 mL; 95% CI -400 to 283; P = 0.90) were not different. Six patients in each group developed acute respiratory distress syndrome (ARDS) (risk ratio 0.96; 95% CI 0.35 to 2.64; P = 0.95). Length of ICU stay (HES vs. lactated Ringer's: 28 vs. 24 days; P = 0.80) and length of hospital stay (31 vs. 29 days; P = 0.57) were similar. Twenty-eight-day mortality was 4 patients in each group (risk ratio 0.96; 95% CI 0.27 to 4.45; P = 0.95), and in-hospital mortality was 8 in the HES group vs. 5 patients in the lactated Ringer's group (hazard ratio 1.86; 95% CI 0.56 to 6.19; P = 0.31). CONCLUSIONS: There was no evidence that early fluid resuscitation with balanced HES 130/0.4 (6%) in addition to lactated Ringer's solution would lead to a volume-sparing effect in severe burn injury. Together with the findings that early renal function, incidence of ARDS, length of stay, and mortality were not negatively influenced by HES in this setting, balanced HES 130/0.4 (6%) plus lactated Ringer's solution could not be considered superior to lactated Ringer's solution alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT01012648.

Association of intraoperative transfusion of blood products with mortality in lung transplant recipients.

BACKGROUND: The impact of intraoperative transfusion on postoperative mortality in lung transplant recipients is still elusive. METHODS: Univariate and multivariate analysis were performed to investigate the influence of red blood cells (RBCs) and fresh frozen plasma (FFP) on mortality in 134 consecutive lung transplants recipients from September 2003 until December 2008. RESULTS: Intraoperative transfusion of RBCs and FFP was associated with a significant increase in mortality with odds ratios (ORs) of 1.10 (1.03 to 1.16, P = 0.02) and 1.09 (1.02 to 1.15, P = 0.03), respectively. For more than four intraoperatively transfused RBCs multivariate analysis showed a hazard ratio for mortality of 3.8 (1.40 to 10.31, P = 0.003). Furthermore, non-survivors showed a significant increase in renal replacement therapy (RRT) (36.6% versus 6.9%, P <0.0001), primary graft dysfunction (PGD) (39.3% versus 5.9%, P <0.0001), postoperative need of extracorporeal membrane oxygenation (ECMO) (26.9% versus 3.1%, P = 0.0019), sepsis (24.2% versus 4.0%, P = 0.0004), multiple organ dysfunction syndrome (MODS) (26.9% versus 3.1%, P <0.0001), infections (18.1% versus 0.9%, P = 0.0004), retransplantation (12.1% versus 6.9%, P = 0.039) and readmission to the ICU (33.3% versus 12.8%, P = 0.024). CONCLUSIONS: Intraoperative transfusion is associated with a strong negative influence on outcome in lung transplant recipients.