Impact of a remifentanil supply shortage on mechanical ventilation in a tertiary care hospital: a retrospective comparison.

BACKGROUND: The continuous administration of opioids in critical care patients is a common therapy for the tolerance of mechanical ventilation. Opioid choice has a crucial impact on the length of mechanical ventilation. Owing to its very short context-sensitive half-life, remifentanil widens the available options for sedoanalgetic strategies. Supply disruption of such established intensive care medication has been reported to worsen clinical outcomes. METHODS: This retrospective study investigated the influence of a nationwide supply shortage of remifentanil on mechanical ventilation and ventilation-associated outcomes at three perioperative intensive care units (ICUs) in a tertiary care hospital in Vienna. Two groups were followed: patients admitted to the ICU during the remifentanil shortage (July 1, 2016 to September 30, 2016) and a control group one year after the remifentanil shortage (July 1, 2017 to September 30, 2017). Included patients were adults, received mechanical ventilation for at least 6 h, were admitted less than 90 days in the respective ICU, and survived their admission. RESULTS: For comparison, Poisson count regression models and logistic regression models were computed. To compensate for multiple testing, the significance level was split (0.02 for the primary and 0.006 for secondary outcome parameters). Patients in the remifentanil shortage group received significantly longer mechanical ventilation (risk ratio 2.19, 95% confidence interval 2.14-2.24, P <0.001) with significantly prolonged ICU stay (P <0.001), days with non-invasive ventilation (P <0.001), and length of hospital stay (P <0.001). No significant difference was found in the occurrence of pneumonia (P = 0.040) and sepsis (P = 0.061). A greater proportion of patients in the shortage group underwent secondary tracheostomy (P <0.001). CONCLUSIONS: The remifentanil shortage caused a significant impairment of essential outcome parameters in the ICU.

Inflammatory response and oxidative stress during liver resection.

BACKGROUND: Postoperative complications are still a major concern after liver resection (LR). Systemic inflammation and deregulated reactive oxygen species during major abdominal surgery may impair outcome after hepatectomy. METHODS: Patients undergoing LR were included in this study (n = 40). Oxidative stress (OS) was measured peri- and post-operatively as static oxidation-reduction potential markers (sORP) and antioxidant capacity ORP (cORP) by using the RedoxSYS Diagnostic system. Furthermore, Th1- and Th2-specific cytokines were assessed. RESULTS: Whereas there was no significant change in systemic sORP during LR and in the early postoperative course, there was a substantial decrease of cORP immediately post-surgery, and on postoperative days 1 and 3 (p<0.001). OS response was tightly regulated, as there was a significant correlation between sORP and cORP (p<0.0001; R2:0.457). An increase of OS (sORP) after LR of more than 3 mV was predictive for severe postoperative complications (53.8% vs. 12.5; p = 0.017). There was a significantly higher IL-2 (p = 0.006) and IL-5 (p = 0.001) increase during hepatectomy in patients who developed a severe morbidity. CONCLUSION: Antioxidant capacity remained stable during LR but dropped during the post-surgical period, suggesting a consumption of antioxidants to maintain OS within healthy range. Severe postoperative complications were associated with a pronounced inflammatory response during surgery.

Plasma levels of chemokine ligand 20 and chemokine receptor 6 in patients with sepsis: A case control study.

BACKGROUND: Chemokine ligand 20 (CCL20) is a chemokine released by mainly liver and blood leucocytes. Particularly under pro-inflammatory circumstances it triggers chemotaxis of lymphocytes and dendritic cells via activating receptor chemokine receptor 6 (CCR6) that is specific to it. In experimental sepsis models, the chemokine-receptor pair has been identified as a potential pathophysiological axis affecting mortality. OBJECTIVE: Measurement of CCL20 and CCR6 plasma levels in septic patients compared with postsurgical, nonseptic patients. DESIGN: Case control study. SETTING: Surgical ICUs of the Department of Anaesthesiology, General Hospital of Vienna, Vienna, Austria. PATIENTS: Plasma levels were measured in 46 patients with sepsis, severe sepsis or septic shock according to current American College of Chest Physicians/Society of Critical Care Medicine criteria at the day of sepsis onset. Plasma levels in 36 postsurgical controls without sepsis admitted to the ICU were investigated. Plasma concentrations were determined by using commercially available ELISA kits. Data are given as median and interquartile range (IQR). MAIN OUTCOME MEASURES: CCL20 and CCR6 plasma levels. RESULTS: CCL20 plasma levels were significantly increased in the sepsis group: 220.9 pg ml (IQR, 72.8 to 540.1) compared with the ICU controls: 37.0 pg ml (IQR 6.5 to 83.6) (P < 0.0001). Significantly elevated CCR6 levels were found in the sepsis group: 2.47 ng ml (IQR 0.92 to 5.54) compared with the controls: 0.59 ng ml (IQR 0.17 to 1.48) (P < 0.0001). Both CCL20 and CCR6 correlated with the maximum sequential organ failure assessment score (CCL20: P < 0.0001, CCR6: P < 0.0001). Length of ICU admission depended significantly on the logarithm of CCR6 (P = 0.008) and sequential organ failure assessment maximum (P < 0.0001). CONCLUSION: There were early increased plasma concentrations of CCL20 and CCR6 in patients with sepsis. CCL20 and CCR6 correlate with severity of illness in ICU patients. Levels of CCR6 predicted the length of patients' admission.

Transection Speed and Impact on Perioperative Inflammatory Response - A Randomized Controlled Trial Comparing Stapler Hepatectomy and CUSA Resection.

BACKGROUND: Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear. MATERIALS AND METHODS: This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality. RESULTS: Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020). CONCLUSIONS: Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time. TRIAL REGISTRATION: ClinicalTrials.gov NCT01785212.

Liver transplantation reverses hypergammaglobulinemia in patients with chronic hepatic failure.

INTRODUCTION: Sparse data are available about the effect of therapy methods on antibody levels in patients with liver failure. The aim of this study was to determine serum immunoglobulin concentrations in patients with chronic hepatic failure (CHF), acute- (ALF), or acute-on-chronic liver failure (ACLF) and to evaluate the impact of MARS treatment or liver transplantation (LT) on antibody levels. MATERIALS AND METHODS: We followed ten patients with ALF, twelve with ACLF and 18 with CHF. Eight patients with ALF and seven with ACLF underwent MARS therapy, whereas the rest received LT. 13 healthy volunteers served as controls. Serum antibody concentrations were measured using ELISA-technique. RESULTS: Median serum levels of IgA, IgG and IgM were significantly increased in patients with CHF compared to ALF or controls (P<0.02, P<0.01, and P<0.01). IgM and IgG concentrations were also significantly elevated in patients with CHF compared to ACLF (IgM, 3.7 vs. 1 g/L, P<0.001; IgG, 8.7 vs. 3.1 g/L, P=0.004). Immediately after LT a significant decrease of IgA (6.9 vs. 3.1 g/L, P=0.004), IgG (8.7 vs. 5.1 g/L, P=0.02) and IgM (3.7 vs. 1.8 g/L, P=0.001) was detected in patients with CHF and antibody levels further decreased the days after LT reaching levels comparable to healthy individuals. MARS treatment had no apparent effect on the immunoglobulin profile in patients with ALF or ACLF. CONCLUSION: We provide evidence that LT reverses hypergammaglobulinemia in patients suffering from CHF within one day, which could be explained to a reconstituted hepatic antibody clearance, whereas MARS treatment has no immediate effect on immunoglobulin levels.

Increased plasma vaspin concentration in patients with sepsis: an exploratory examination.

INTRODUCTION: Vaspin (visceral adipose tissue-derived serpin) was first described as an insulin-sensitizing adipose tissue hormone. Recently its anti-inflammatory function has been demonstrated. Since no appropriate data is available yet, we sought to investigate the plasma concentrations of vaspin in sepsis. MATERIALS AND METHODS: 57 patients in intensive care, fulfilling the ACCP/SCCM criteria for sepsis, were prospectively included in our exploratory study. The control group consisted of 48 critically ill patients, receiving intensive care after trauma or major surgery. Patients were matched by age, sex, weight and existence of diabetes before statistical analysis. Blood samples were collected on the day of diagnosis. Vaspin plasma concentrations were measured using a commercially available enzyme-linked immunosorbent assay. RESULTS: Vaspin concentrations were significantly higher in septic patients compared to the control group (0.3 (0.1-0.4) ng/mL vs. 0.1 (0.0-0.3) ng/mL, respectively; P<0.001). Vaspin concentration showed weak positive correlation with concentration of C-reactive protein (CRP) (r=0.31, P=0.002) as well as with SAPS II (r=0.34, P=0.002) and maximum of SOFA (r=0.39, P<0.001) scoring systems, as tested for the overall study population. CONCLUSION: In the sepsis group, vaspin plasma concentration was about three-fold as high as in the median surgical control group. We demonstrated a weak positive correlation between vaspin and CRP concentration, as well as with two scoring systems commonly used in intensive care settings. Although there seems to be some connection between vaspin and inflammation, its role in human sepsis needs to be evaluated further.

Increased chemokine excretion in patients suffering from chronic kidney disease.

During chronic kidney disease (CKD) leukocytes attracted by chemokines can migrate into the kidney and further aggravate renal affliction by releasing proinflammatory and profibrotic factors. We therefore sought to investigate serum and urine chemokine levels of 114 patients with CKD and 21 healthy volunteers to examine their possible suitability as biomarkers for monitoring disease course and patient's risk assessment. Analyzed chemokines were CCL17, CCL20, CCL22, and CXCL11, which are especially involved in the development of chronic renal failure. Our results showed elevated fractional CCL22 excretion levels in patients with CKD stages 2-5 compared with healthy controls. Furthermore, fractional CCL22 excretion was increased in patients with CKD stages 4 and 5 compared with stages 1-3. Fractional CCL20 excretion showed a significant elevation in patients with CKD stage 5 compared with healthy individuals and patients with CKD stages 1-3. Fractional CXCL11 excretion was significantly elevated in patients with CKD stages 4 and 5 compared with healthy controls and patients with CKD stages 1-3. Moreover, receiver operating characteristic curve analysis showed the potential of chemokine excretion to predict various CKD stages (area under the curve [AUC] 0.835, P < 0.0001 for CCL22, stage 1 and higher; AUC 0.6887, P = 0.0007 for CCL20, stage 3 and higher; AUC 0.7549, P = 0.0003 for CXCL11, stage 3 and higher). Our results further uncovered trends in varying chemokine serum and excretion levels in different CKD etiologies. In conclusion, monitoring fractional chemokine excretion might be suitable for following CKD course and hence promoting individually adjusted treatment planning.

Increased plasma zonulin in patients with sepsis.

INTRODUCTION: Zonulin is a eukaryotic protein structurally similar to Vibrio cholerae's zonula occludens toxin. It plays an important role in the opening of small intestine tight junctions. The loss of gut wall integrity during sepsis might be pivotal and has been described in various experimental as well as human studies. Increased levels of zonulin could be demonstrated in diseases associated with increased intestinal inflammation, such as celiac disease and type 1 diabetes. We therefore investigated the role of plasma levels of zonulin in patients with sepsis as a non-invasive marker of gut wall integrity. MATERIALS AND METHODS: Plasma level of zonulin was measured in 25 patients with sepsis, severe sepsis or septic shock according to ACCP/SCCM criteria at the first day of diagnosed sepsis. 18 non-septic post-surgical ICU-patients and 20 healthy volunteers served as control. Plasma levels were determined by using commercially available ELISA kit. Data are given as median and interquartile range (IQR). RESULTS: Significantly higher plasma concentration of zonulin were found in the sepsis group: 6.61 ng/mL (IQR 3.51-9.46), as compared to the to the post-surgical control group: 3.40 ng/mL (IQR 2.14-5.70) (P = 0.025), as well as to the healthy group: 3.55 ng/mL (IQR 3.14-4.14) (P = 0.008). CONCLUSION: We were able demonstrate elevated levels of plasma zonulin, a potential marker of intestinal permeability in septic patients. Increased zonulin may serve as an additional mechanism for the observed increased intestinal permeability during sepsis and SIRS.