Alpha1-microglobulin as an early biomarker of sepsis-associated acute kidney injury: a prospective cohort study.

BACKGROUND: Sepsis emerges as the leading risk factor for acute kidney injury (AKI) development in critically ill patients. Much effort has been invested so far on early diagnosis of AKI using promising biomarkers. This study aimed to determine whether urine alpha1-microglobulin (α1m), a lipocaline member previously used as an indicator of proximal tubular dysfunction, can early predict the development of sepsis-associated AKI (SAAKI) in critically ill patients. METHODS: A prospective, observational study was conducted in a single center Intensive Care Unit (ICU). Patients with normal renal function admitted to the ICU followed for sepsis and AKI development. Urine α1m levels were analyzed in pooled samples from 24-hour urine collections on sepsis onset and at various time points thereafter. The diagnostic performance of urine α1m was assessed using thenonparametriccalculation of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: Among 286 critically ill patients admitted to our ICU in a year, 45 patients with sepsis met the inclusion criteria. SAAKI developed in 16 septic patients (35.6%). Urine α1m levels were significantly elevated in all septic patients (average value of all samples on the day of sepsis: 46.02 ± 7.17 mg/l) and showed a trend to increase in patients who finally developed SAAKI. The AUC for SAAKI prediction according to α1m urine levels 24-hours before SAAKI onset was 0.739 (sensitivity 87.5%, specificity 62.07%, cutoff level 47.9 mg/l). Urine α1m 24-hours before SAAKI, serum creatinine on sepsis onset and Acute Physiology and Chronic Health Evaluation II (APACHE II) score on sepsis onset emerged as the most powerful independent predictors of SAAKI. The combination of these three parameters improved the AUC for SAAKI prediction to 0.944. CONCLUSION: Urine α1m levels might help in the early prediction of SAAKI development and may prove useful biomarker. The pathogenetic implications of α1m in sepsis and SAAKI need further investigation. Hippokratia 2014; 18 (3): 262-268.

The impact of fluid restriction policy in reducing the use of red blood cells in cardiac surgery.

Hemodilution contributes significantly to transfusion requirements in patients undergoing CABG under CPB. We hypothesised that restriction of parenteral fluids in comparison to a liberal fluid administration policy leads to less use of packed red cells in CABG operations supported by cell salvage. After consent and approval, 130 patients operated under equal conditions were assigned prospectively and randomly either for a restrictive protocol for intravenous fluid administration (group A, 65 pts) or not (group B, 65 pts). Transfusion guidelines were common for the two groups. The volumes of intravenous fluids, priming, "extra" volume on pump and cardioplegic solution and the volume of urine were recorded. Net erythrocyte volume loss was calculated. The number of the transfused PRC was analyzed as a continuous variable. "Transfusion" was analyzed as a categorical characteristic. Significant difference existed between groups for the fluids administered intravenously until the initiation of CPB and for fluid balance after CPB. Intraoperatively transfused units were significantly lower in A (0.32 +/- 0.77 vs 1.26 +/- 1.05 u/per pt; p<0.0001). Transfused patients were also significantly lower in A (11/65 vs 44/65; p<0.0001). In both groups, the values of hematocrit were statistically decreased. The greatest difference compared to the preoperative values was observed after CPB (from 40.8 +/- 4.2 to 21.9 +/- 3.6 for A, and from 40.2 +/- 3.7 to 19.7 +/- 3.3 for B ; p<0.0001 for both). For these lowest values, significant difference existed between groups (p<0,001) while the difference in the hematocrit values to the end of operation was insignificant. Transfusion in ICU showed no significant difference among groups. Hours of mechanical ventilation in ICU were ranging from 5 to 29 (mean = 10.0, median = 9) for A and from 5 to 42 (mean = 14.8, median = 10) for B. Length of stay in ICU in nights for group A was ranging from 1 to 10 (mean = 2.7, median = 2) and for group B was ranging from 1 to 6 (mean = 3.5, median = 2). In conclusion, reduction of transfusions in CABG operations is feasible when a restrictive protocol for intravenous fluids is applied.

The propofol infusion 'syndrome' in intensive care unit: from pathophysiology to prophylaxis and treatment.

Propofol is a short-acting intravenous anesthetic agent widely used for sedation in anesthesia and intensive care. However, during the last 15 years there have been quite a lot of publications reporting unexplained deaths among pediatric and adult critically ill patients. These cases shared common symptoms and signs unrelated with initial admission diagnosis and were under long-term propofol infusion at high doses. A new syndrome called 'propofol infusion syndrome' was defined, including cardiovascular instability, metabolic acidosis, hyperkalaemia and rhabdomyolysis, with no evidence for other known causes of myocardial failure. One common denominator in these patients was the presence of hypoxia and tissue hypoperfusion. It seems that during states of increased metabolic demand, the reduced energy production related to an inhibitory propofol action at the level of mitochondrial oxidative phosphorylation and lipid metabolism may lead to the manifestation of the syndrome. Furthermore, cases of early toxicity due to failure in cellular energy production with development of lactic acidosis have been also described during anesthesia. For the above reasons, recommendations for the limitation of propofol use have been devised by various institutions, whereas physicians need to be cautious when using prolonged propofol sedation and alert for early signs of toxicity.

Changes in blood flow of anterior and middle cerebral arteries following carotid endarterectomy: a transcranial Doppler study.

AIM: The aim of the present study was to evaluate the changes in blood flow of anterior and middle cerebral arteries following carotid endarterectomy, using transcranial Doppler (TCD) flow studies. PATIENTS AND METHODS: This study included 100 patients (72 men, mean age 65 years) who underwent carotid endarterectomy because of high-grade carotid stenosis or symptoms of ischemic stroke. Endarterectomy was performed by a distal shunt between the common carotid and internal carotid arteries. Blood flow in the anterior and middle cerebral arteries was assessed by TCD preoperatively and also in the postoperative period (1st and 4th day; 1st, 6th, and 12th month). Collateral circulation in the Willis circle was evaluated by common carotid compression. RESULTS: Patients with bilateral carotid stenosis > or =70% exhibited a significantly increased flow velocity in the ipsilateral anterior cerebral artery (ACA), middle cerebral artery (MCA), and in the contralateral ACA. Patients with entirely occluded contralateral internal carotid artery showed the most pronounced changes in cerebral hemodynamics. Blood flow velocities returned to the preoperative values at 1 to 12 months following endarterectomy. Hyperperfusion syndrome was manifested in 14 patients, who exhibited significantly higher flow velocities in the ipsilateral MCA compared with asymptomatic patients. CONCLUSIONS: A transient bilateral increase of blood flow velocity in the anterior part of the Willis circle may often occur in the immediate postoperative period following carotid endarterectomy. Although its clinical significance is not entirely understood, this increase may be associated with cerebral hyperperfusion syndrome.

Non-programmed clamping of superior vena cava. The anesthesiologist's Achilles' heel.

This case presentation focuses on the hemodynamic alterations due to acute clamping of superior vena cava (SVC) during a right pneumonectomy for lung cancer and on the alternatives for drug administration. In a 71-yr-old female patient without clinical manifestations of SVC syndrome, this large vein was clamped for 22 minutes for patch placement after sudden and unpredictable hemorrhage. The patient became acutely cyanotic and edematous in the face and upper extremities, arterial blood pressure dropped and the venous pressure in the right internal jugular vein was elevated. Drugs for managing the patient were given endobronchially and via an established right atrium line. Postoperatively, no neurologic deficit was noted. This case demonstrates the difficulties for managing patients without superior vena cava syndrome in which acute, non-programmed intra-operative SVC clamping is performed, as this is followed by systemic and brain hemodynamic deteriorations that may lead to bad outcome.

Coronary sinus venoarterial CO2 difference in different hemodynamic states.

Myocardial metabolic rate and coronary flow are closely related limiting thus the diagnostic value of coronary sinus saturation monitoring as an indicator of flow. Regional venoarterial CO2 gradient was found elevated during low flow in various clinical and experimental conditions, in animals and humans. This study was undertaken to examine the impact of the variations of cardiac mechanical work on veno-arterial CO2 content and partial pressure difference (deltaPCO2) of the coronary sinus blood. Twenty-seven patients of either sex (m/f = 21/6), undergoing coronary artery bypass grafting under extracorporeal circulation, were studied. Monitoring included a Swan-Ganz catheter and a coronary sinus line. The correct position of the late was verified by the waveform displayed in the monitor. Immediately after cannulae placement, a hemodynamic profile was obtained and simultaneous arterial and coronary sinus sampling for blood gas analysis was done in an ABL 720 (Radiometer Copenhagen) analyzer. A second collection of the same data was obtained five minutes later with the patients in a slight "head-down" position. Conditions for exclusion was intersample variation of hemoglobin's concentration greater than 15% and sodium ion concentration difference greater than 10% of the greater value. Arteriovenous oxygen partial pressure difference (deltaP(a-cs)O2), veno-arterial carbon dioxide partial pressure difference (deltaP(cs-a)CO2), O2 & CO2 content difference and heart's respiratory quotient were calculated and correlated to cardiac output (CO) and the other hemodynamic parameters. Statistical analysis employed t-paired test and linear regression. No ischemia was detected during sampling. "Head-down" position had a significant impact to all hemodynamic parameters except heart rate. In both data rows, although CO ranged widely and altered significantly, coronary sinus oxygen saturation and arteriovenous O2 content difference were stable and showed insignificant correlations to all the hemodynamic parameters that were studied. Carbon dioxide content difference (coronary sinus-arterial) showed a trending of decrease with higher flow. DeltaP(cs-a)CO2 appeared stable and independent of flow. Finally, respiratory quotient decreased significantly from 0.91 +/- 0.4 to 0.86 +/- 0.4 (mean +/- SD; p < 0.05). The heart's high basal oxygen consumption and the almost near hemoglobin's desaturation transcoronary extraction of oxygen limits the value of coronary sinus saturation monitoring as indicator of coronary flow. Heart's little extraction reserve is faced with coronary flow reserve. In the physiologic range and under the conditions of anesthesia, elevated CO2 production is accompanied with increased coronary flow. Under these circumstances, deltaP(cs-a)CO2 appears stable and is not suitable for clinical decisions concerning heart's coronary flow.