Jan Bláha

Comparison of Three Protocols for Tight Glycemic Control in Cardiac Surgery Patients

OBJECTIVE We performed a randomized trial to compare three insulin-titration protocols for tight glycemic control (TGC) in a surgical intensive care unit: an absolute glucose (Matias) protocol, a relative glucose change (Bath) protocol, and an enhanced model predictive control (eMPC) algorithm. RESEARCH DESIGN AND METHODS A total of 120 consecutive patients after cardiac surgery were randomly assigned to the three protocols with a target glycemia range from 4.4 to 6.1 mmol/l. Intravenous insulin was administered continuously or in combination with insulin boluses (Matias protocol). Blood glucose was measured in 1- to 4-h intervals as requested by the protocols. RESULTS The eMPC algorithm gave the best performance as assessed by time to target (8.8 ± 2.2 vs. 10.9 ± 1.0 vs. 12.3 ± 1.9 h; eMPC vs. Matias vs. Bath, respectively; P < 0.05), average blood glucose after reaching the target (5.2 ± 0.1 vs. 6.2 ± 0.1 vs. 5.8 ± 0.1 mmol/l; P < 0.01), time in target (62.8 ± 4.4 vs. 48.4 ± 3.28 vs. 55.5 ± 3.2%; P < 0.05), time in hyperglycemia >8.3 mmol/l (1.3 ± 1.2 vs. 12.8 ± 2.2 vs. 6.5 ± 2.0%; P < 0.05), and sampling interval (2.3 ± 0.1 vs. 2.1 ± 0.1 vs. 1.8 ± 0.1 h; P < 0.05). However, time in hypoglycemia risk range (2.9–4.3 mmol/l) in the eMPC group was the longest (22.2 ± 1.9 vs. 10.9 ± 1.5 vs. 13.1 ± 1.6; P < 0.05). No severe hypoglycemic episode (<2.3 mmol/l) occurred in the eMPC group compared with one in the Matias group and two in the Bath group. CONCLUSIONS The eMPC algorithm provided the best TGC without increasing the risk of severe hypoglycemia while requiring the fewest glucose measurements. Overall, all protocols were safe and effective in the maintenance of TGC in cardiac surgery patients.

The Use of Continuous Glucose Monitoring Combined with Computer-Based eMPC Algorithm for Tight Glucose Control in Cardiosurgical ICU

Aim. In postcardiac surgery patients, we assessed the performance of a system for intensive intravenous insulin therapy using continuous glucose monitoring (CGM) and enhanced model predictive control (eMPC) algorithm. Methods. Glucose control in eMPC-CGM group (n = 12) was compared with a control (C) group (n = 12) treated by intravenous insulin infusion adjusted according to eMPC protocol with a variable sampling interval alone. In the eMPC-CGM group glucose measured with a REAL-Time CGM system (Guardian RT) served as input for the eMPC adjusting insulin infusion every 15 minutes. The accuracy of CGM was evaluated hourly using reference arterial glucose and Clarke error-grid analysis (C-EGA). Target glucose range was 4.4–6.1 mmol/L. Results. Of the 277 paired CGM-reference glycemic values, 270 (97.5%) were in clinically acceptable zones of C-EGA and only 7 (2.5%) were in unacceptable D zone. Glucose control in eMPC-CGM group was comparable to C group in all measured values (average glycemia, percentage of time above, within, and below target range,). No episode of hypoglycemia (<2.9 mmol) occurred in eMPC-CGM group compared to 2 in C group. Conclusion. Our data show that the combination of eMPC algorithm with CGM is reliable and accurate enough to test this approach in a larger study population.

Perioperative Tight Glucose Control Reduces Postoperative Adverse Events in Nondiabetic Cardiac Surgery Patients

CONTEXT Tight glucose control (TGC) reduces morbidity and mortality in patients undergoing elective cardiac surgery, but only limited data about its optimal timing are available to date. OBJECTIVE The purpose of this article was to compare the effects of perioperative vs postoperative initiation of TGC on postoperative adverse events in cardiac surgery patients. DESIGN This was a single center, single-blind, parallel-group, randomized controlled trial. SETTINGS The setting was an academic tertiary hospital. PARTICIPANTS Participants were 2383 hemodynamically stable patients undergoing major cardiac surgery with expected postoperative intensive care unit treatment for at least 2 consecutive days. INTERVENTION Intensive insulin therapy was initiated perioperatively or postoperatively with a target glucose range of 4.4 to 6.1 mmol/L. MAIN OUTCOME MEASURES Adverse events from any cause during postoperative hospital stay were compared. RESULTS In the whole cohort, perioperatively initiated TGC markedly reduced the number of postoperative complications (23.2% vs 34.1%, 95% confidence interval [CI], 0.60-0.78) despite only minimal improvement in glucose control (blood glucose, 6.6 ± 0.7 vs 6.7 ± 0.8 mmol/L, P < .001; time in target range, 39.3% ± 13.7% vs 37.3% ± 13.8%, P < .001). The positive effects of TGC on postoperative complications were driven by nondiabetic subjects (21.3% vs 33.7%, 95% CI, 0.54-0.74; blood glucose 6.5 ± 0.6 vs 6.6 ± 0.8 mmol/L, not significant; time in target range, 40.8% ± 13.6% vs 39.7% ± 13.8%, not significant), whereas no significant effect was seen in diabetic patients (29.4% vs 35.1%, 95% CI, 0.66-1.06) despite significantly better glucose control in the perioperative group (blood glucose, 6.9 ± 1.0 vs 7.1 ± 0.8 mmol/L, P < .001; time in target range, 34.3% ± 12.7% vs 30.8% ± 11.5%, P < .001). CONCLUSIONS Perioperative initiation of intensive insulin therapy during cardiac surgery reduces postoperative morbidity in nondiabetic patients while having a minimal effect in diabetic subjects.

Evaluating Glycemic Control Algorithms by Computer Simulations

BACKGROUND Numerous guidelines and algorithms exist to achieve glycemic control. Their strengths and weaknesses are difficult to assess without head-to-head comparison in time-consuming clinical trials. We hypothesized that computer simulations may be useful. METHODS Two open-label randomized clinical trials were replicated using computer simulations. One study compared performance of the enhanced model predictive control (eMPC) algorithm at two intensive care units in the United Kingdom and Belgium. The other study compared three glucose control algorithms-eMPC, Matias (the absolute glucose protocol), and Bath (the relative glucose change protocol)-in a single intensive care unit. Computer simulations utilized a virtual population of 56 critically ill subjects derived from routine data collected at four European surgical and medical intensive care units. RESULTS In agreement with the first clinical study, computer simulations reproduced the main finding and discriminated between the two intensive care units in terms of the sampling interval (1.3 h vs. 1.8 h, United Kingdom vs. Belgium; P < 0.01). Other glucose control metrics were comparable between simulations and clinical results. The principal outcome of the second study was also reproduced. The eMPC demonstrated better performance compared with the Matias and Bath algorithms as assessed by the time when plasma glucose was in the target range between 4.4 and 6.1 mmol/L (65% vs. 43% vs. 42% [P < 0.001], eMPC vs. Matias vs. Bath) without increasing the risk of severe hypoglycemia. CONCLUSIONS Computer simulations may provide resource-efficient means for preclinical evaluation of algorithms for glycemic control in the critically ill.

Anesthesia for Cesarean Delivery in the Czech Republic: A 2011 National Survey

BACKGROUND:The purpose of this national survey was to determine current anesthesia practices for cesarean delivery in the Czech Republic. METHODS:In November 2011, we invited all departments of obstetric anesthesia in the Czech Republic to participate in a prospective study to monitor consecutive peripartum obstetric anesthesia procedures. Data were recorded online in the TrialDB database (Yale University, New Haven, CT). RESULTS:The response rate was 51% (49 of 97 departments); participating centers represented 60% of all births in the country during the study period. There were 1943 cases of peripartum anesthesia care, of which 1166 cases (60%) were anesthesia for cesarean delivery. Estimates were weighted based on population distribution of cesarean delivery among types of participating centers. Neuraxial anesthesia was used in 55.6% (95% confidence interval [CI], 52.8%–58.5%); the distribution of anesthesia techniques differed among type of participating center. The rate of neuraxial anesthesia in university hospitals was 55.6% (95% CI, 51.5%–59.6%), 32.4% (95% CI, 26.4%–39.0%) in regional hospitals, and 60.7% (95% CI, 55.2%–66.0%) in local hospitals. The reasons for cesarean delivery under general anesthesia were emergency procedure (67%), refusal of neuraxial blockade by parturient (30%), failure of neuraxial anesthesia (6%), and preoperative administration of low-molecular-weight heparin (3%). Postcesarean analgesia was primarily provided by systemic opioid (66%) and nonopioid analgesics (61%), solely or in combination. Epidural postoperative analgesia was used in 14% of cases. Compared with national neuraxial anesthesia rate data published in the 1990s (6.7% in 1993), there has been an upward trend in the use of neuraxial anesthesia for cesarean delivery during the 21st century (40.5% in 2000) in the Czech Republic. CONCLUSIONS:The rate of neuraxial anesthesia use for cesarean delivery has increased in the Czech Republic in the last 2 decades. However, the current rate of general anesthesia is high compared with other Western countries.

The effect of adjusting tracheal tube cuff pressure during deep hypothermic circulatory arrest: a randomised trial.

BACKGROUND Regular endotracheal tube cuff monitoring may prevent silent aspiration. OBJECTIVES We hypothesised that active management of the cuff of the tracheal tube during deep hypothermic cardiac arrest would reduce silent subglottic aspiration. We also determined to study its effect on postoperative mechanical ventilation and the incidence of postoperative positive tracheal cultures. DESIGN A randomised clinical trial. SETTING The study was conducted in a University Teaching Hospital from September 2008 to November 2009. PATIENTS Twenty-four patients undergoing elective pulmonary endarterectomy were included in the study. INTERVENTION After induction of general anaesthesia and tracheal intubation, the cuff of the tracheal tube was inflated to 25 cmH2O. Following this, 1 ml of methylene blue dye diluted in 2 ml of physiological saline was injected into the hypopharynx. Patients were randomly assigned to active cuff management during cooling and warming (where cuff pressure was monitored and the cuff was reinflated if it dropped below 20 cmH2O, or deflated if pressure exceeded 30 cmH2O) or passive monitoring (where cuff pressure was monitored but volume was not altered). Before weaning from cardiopulmonary bypass, fibreoptic bronchoscopy was performed. Silent aspiration was then diagnosed if blue dye was seen in the trachea below the cuff of the tube. MAIN OUTCOME MEASURES The primary aim of this study was to determine the incidence of silent aspiration. Secondary outcomes included duration of postoperative mechanical ventilation of the lungs and incidence of positive culture of tracheal aspirate. RESULTS Active cuff management patients were younger than controls (51.2 ± 11.6 vs. 63.2 ± 9 years, P = 0.028), but otherwise the two groups were similar. The primary endpoint was reached because we showed that silent aspiration was significantly less frequent in the study group (0/12 vs. 8/12 patients, P = 0.001). Significantly lower intracuff pressures were measured in the control group patients at several timepoints during cooling, just before hypothermic arrest and at all timepoints during rewarming. CONCLUSION We recommend that the cuff of the tracheal tube should be checked regularly during surgery under deep hypothermia, and the cuff pressure adjusted as required.

Four crystal structures of human LLT1, a ligand of human NKR-P1, in varied glycosylation and oligomerization states

Four crystal structures of human LLT1, a ligand of human NKR-P1, are reported.

Use of high-thoracic epidural analgesia in pulmonary endarterectomy: a randomized feasibility study.

BACKGROUND The suitability of combined high-thoracic epidural anesthesia for pulmonary endarterectomy was studied. METHODS A prospective randomized clinical study was conducted in a university medical center from November 2005 to December 2006. The primary endpoint of this study was to evaluate perioperative hemodynamic data; secondary endpoints were to evaluate the duration of artificial ventilation, length of stay in the intensive care unit, and the impact on postoperative morbidity and mortality. RESULTS The 16 patients in the study group received high-thoracic epidural anesthesia plus general anesthesia; the 16 control patients received total intravenous anesthesia alone. Hemodynamic parameters and drug use, as well as the time to extubation, rate of complications, postoperative pain, the length of intensive care unit stay, and mortality, were recorded. The 2 groups were comparable with respect to hemodynamic stability during induction of anesthesia. The study group patients had significantly lower sufentanil consumption (mean +/- SD, 2.1 +/- 0.7 microg/kg versus 9.1 +/- 3.1 microg/kg; P <.001), a shorter period of artificial ventilation (34 +/- 35 hours versus 52 +/- 49 hours; P = .0318), and lower postoperative pain scores at 3 hours (0.10 +/- 0.26 versus 0.93 +/- 1.38; P = .015), 12 hours (0.14 +/- 0.53 versus 0.93 +/- 0.79; P = .002), and 24 hours (0.35 +/- 0.49 versus 1.33 +/- 1.04; P = .007). CONCLUSIONS This study has shown that combined epidural and general anesthesia is a suitable anesthetic option in patients who are selected for pulmonary endarterectomy. It provides hemodynamic stability and reduces the duration of tracheal intubation postoperatively and improves postoperative pain relief, although this option has not been shown to decrease either the length of the intensive care unit stay or mortality.

Crystal structure of native β‐N‐acetylhexosaminidase isolated from Aspergillus oryzae sheds light onto its substrate specificity, high stability, and regulation by propeptide

β‐N‐acetylhexosaminidase from the fungus Aspergillus oryzae is a secreted extracellular enzyme that cleaves chitobiose into constituent monosaccharides. It belongs to the GH 20 glycoside hydrolase family and consists of two N‐glycosylated catalytic cores noncovalently associated with two 10‐kDa O‐glycosylated propeptides. We used X‐ray diffraction and mass spectrometry to determine the structure of A. oryzae β‐N‐acetylhexosaminidase isolated from its natural source. The three‐dimensional structure determined and refined to a resolution of 2.3 Å revealed that this enzyme is active as a uniquely tight dimeric assembly further stabilized by N‐ and O‐glycosylation. The propeptide from one subunit forms extensive noncovalent interactions with the catalytic core of the second subunit in the dimer, and this chain swap suggests the distinctive structural mechanism of the enzymes activation. Unique structural features of β‐N‐acetylhexosaminidase from A. oryzae define a very stable and robust framework suitable for biotechnological applications. The crystal structure reported here provides structural insights into the enzyme architecture as well as the detailed configuration of the active site. These insights can be applied to rational enzyme engineering.

Aesthetic Aspects of Early Maps

The contribution is a tribute to Czech Univ. Prof. Karel Kuchar and reminds us of the 35th anniversary, counted from his last public lecture named Aesthetics of Map Production. Unfortunately, Prof. Kuchar was not able to elaborate the issue of aesthetic aspects of cartographic production in further detail. The aim of this contribution is to categorize and summarize this knowledge. The first part mentions the traditional, and we can also say never-ending, discussion on cartography and early maps being a form of art. It is followed by a summary of aesthetic aspects of (not only) early maps (map format, sheet composition, use of space, shapes of map fields and structure of outlines, form of compositional elements, map contents, cartographic language, thematic cartography methods, use of colour and font in maps, author’s style and handwriting). Finally, several pieces of evidence are offered confirming that “early maps” and “computer map production” are not incompatible.