Vladimír Šrámek

Effect of dopexamine on outcome after major abdominal surgery: A prospective, randomized, controlled multicenter study

ObjectiveTo test the hypothesis that dopexamine reduces postoperative mortality and morbidity in high-risk, major abdominal surgery patients, when given to fluid-resuscitated patients starting before the operation and continued for 24 hrs after surgery. DesignProspective, randomized, controlled, double-blind multicenter trial. SettingIntensive care units in 13 hospitals from six European countries. PatientsA total of 412 patients with predefined high-risk criteria, undergoing major abdominal surgery with an expected duration of at least 1.5 hrs. InterventionsThe patients received placebo (n = 140), dopexamine at 0.5 &mgr;g/kg/min (n = 135), or dopexamine at 2.0 &mgr;g/kg/min (n = 137) starting after preoperative hemodynamic stabilization and continued for 24 hrs after surgery. Measurements and Main ResultsThe primary outcome variable was mortality at 28 days. Analysis was by intention to treat. Dopexamine had no effect on mortality (at 28 days, 13%, 7%, and 15%, for the groups receiving placebo, dopexamine at 0.5 &mgr;g/kg/min, and dopexamine at 2.0 &mgr;g/kg/min, respectively), despite the expected dose-dependent hemodynamic responses. No effect was observed on the occurrence of organ dysfunction, duration of intensive care unit stay, or length of hospital stay. ConclusionWe conclude that dopexamine in doses that result in increased cardiac output and oxygen delivery after preoperative stabilization with fluids does not improve outcome after major abdominal surgery compared with fluids alone. Based on post hoc subgroup analysis and stratification according to the number of risk factors, we suggest that the concept should be further tested in patients at higher risk of complications or undergoing emergency surgery.

Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study.

Summary Background Sepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival. Methods We did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1–3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died. Findings In the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1–3), common variants in the FER gene were strongly associated with survival (p=9·7 × 10−8). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5·6 × 10−8 (odds ratio 0·56, 95% CI 0·45–0·69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0·56, 95% CI 0·45–0·69; likelihood ratio test p=3·4 × 10−9, after adjustment for age and stratification by cohort). Mortality was 9·5% in patients carrying the CC genotype, 15·2% in those carrying the TC genotype, and 25·3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined. Interpretation We have identified common variants in the FER gene that associate with a reduced risk of death from sepsis due to pneumonia. The FER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification. Funding European Commission and the Wellcome Trust.

Influence of insulin on glucose metabolism and energy expenditure in septic patients

IntroductionIt is recognized that administration of insulin with glucose decreases catabolic response in sepsis. The aim of the present study was to compare the effects of two levels of insulinaemia on glucose metabolism and energy expenditure in septic patients and volunteers.MethodsGlucose uptake, oxidation and storage, and energy expenditure were measured, using indirect calorimetry, in 20 stable septic patients and 10 volunteers in a two-step hyperinsulinaemic (serum insulin levels 250 and 1250 mIU/l), euglycaemic (blood glucose concentration 5 mmol/l) clamp. Differences between steps of the clamp (from serum insulin 1250 to 250 mIU/l) for all parameters were calculated for each individual, and compared between septic patients and volunteers using the Wilcoxon nonpaired test.ResultsDifferences in glucose uptake and storage were significantly less in septic patients. The differences in glucose oxidation between the groups were not statistically significant. Baseline energy expenditure was significantly higher in septic patients, and there was no significant increase in either step of the clamp in this group; when comparing the two groups, the differences between steps were significantly greater in volunteers.ConclusionA hyperdynamic state of sepsis leads to a decrease in glucose uptake and storage in comparison with healthy volunteers. An increase in insulinaemia leads to an increase in all parameters of glucose metabolism, but the increases in glucose uptake and storage are significantly lower in septic patients. A high level of insulinaemia in sepsis increases glucose uptake and oxidation significantly, but not energy expenditure, in comparison with volunteers.

Continuous venovenous hemodiafiltration (CWHDF) with citrate anticoagulation in the treatment of a patient with acute renal failure, hypercalcemia, and thrombocytopenia

A 72-year-old patient with multiple myeloma was admitted to the intensive care unit because of hypercalcemic crisis and acute renal failure. After 7 days of comprehensive therapy including diuretics, steroids, calcitonin, and intermittent hemodialysis (IHD) with low-calcium dialysate, calcium still reached high levels between IHD treatments and thrombocytopenia developed after chemotherapy. CWHDF with calcium-free bicarbonate dialysate was started. Anticoagulation with 2.2 % citrate was performed in order to chelate calcium, and thus treat the hypercalcemia, and to provide regional anticoagulation, and thus reduce the risk of bleeding due to thrombocytopenia. CWHDF with citrate anticoagulation was continued for 6 days, and standard heparin anticoagulation was started when the hypercalcemia and thrombocytopenia abated.

Glycemia Influences on Glucose Metabolism in Sepsis During Hyperinsulinemic Clamp

BACKGROUND We investigated glucose metabolism in septic patients during hyperglycemic clamps and compared the different levels of insulinemia and glycemia. METHODS In 10 non-diabetic stable septic patients on mechanical ventilation with baseline glycemia >6 mmol/L and continuous insulin infusion, 3 steps of hyperinsulinemic clamp were performed after 8 hours without caloric intake. In step 1, the targets were insulinemia of 250 mIU/L and glycemia of 5 mmol/L; in step 2, insulinemia of 250 mIU/L and glycemia of 10 mmol/L; in step 3, insulinemia of 1250 mIU/L and glycemia of 5 mmol/L. Glucose uptake was calculated as the amount of glucose per time needed to maintain the target level of glycemia. Glucose oxidation was calculated from indirect calorimetry and urinary nitrogen losses. Values are provided as means +/- SD. A two-way analysis of variance and Scheffes method were used for statistical analysis and p < .05 was considered significant. RESULTS At step 1, glucose uptake was lower than at step 2 (3.8 +/- 2.48 mg/kg/min and 7.9 +/- 3.45 mg/kg/min, respectively; p < .001). Glucose oxidation was also lower at step 1 (2.6 +/- 0.98 and 4.2 +/- 1.85 mg/kg/min, respectively; p < .01). Glucose storage was low at step 1 (0.7 +/- 1.39) and increased at step 2 (3.5 +/- 2.18; p < .05). In step 3, glucose uptake was 7.0 +/- 2.1, oxidation was 3.6 +/- 1.37, and storage was 2.9 +/- 2.79. There was no significant difference in all these parameters between steps 2 and 3. Energy expenditure between steps 1, 2 and 3 did not change (2294 + 307.42, 2334 + 341.53, and 2342 + 426.67 kcal/day, respectively). Alanine in plasma dropped significantly (p < .05): 10 mmol/L (311 +/- 55.88 mmol/L) at glycemia compared with 5 mmol/L (390 +/- 76 micromol/L) at insulinemia 250 mIU/L. It did not differ significantly from the values obtained at glycemia 5 mmol/L and insulinemia 1250 mIU/L (348 +/- 70.68 mmol/L). Even if the level of cytokines in sepsis was higher, there was no correlation between the insulin level in plasma (250 and 1250 mIU/L), glycemia (5 and 10 mmol/L) and cytokine level (IL-1beta, IL-2, IL-6, IL-8 and TNFalpha). CONCLUSION At insulinemia 250 mIU/L, a glucose level of 10 mmol/L seems to increase glucose uptake, oxidation, and storage compared with glycemia 5 mmol/L. This glucose uptake and oxidation at glycemia 10 mmol/L is comparable with the effect of extremely high insulinemia (1250 mIU/L) clamped at glycemia 5 mmol/L. A higher level of blood glucose or a high level of insulinemia significantly increases glucose uptake but not energy expenditure.

Quantitative analysis of drug losses administered via nasogastric tube - In vitro study

PURPOSE Drug administration through nasogastric tube (NGT) is a standard practice but the real amount of the delivered drug is unknown. Therefore, we designed a study to determine the losses of various dosage forms administered by different methods through NGT. METHODS In vitro model was used. Five different administration methods (A-E) and six dosage forms (simple compressed tablets - T/S; film coated tablets - T/FC; enteric coated tablets - T/EC; capsules with powder filling - C/P; capsules containing extended release pellets - C/ER; capsules containing gastro-resistant pellets - C/GR) were investigated. Measurement was repeated six times for each drug-method combination. The overall losses were determined by gravimetry. In method A partial losses associated with each step of drug administration were also determined. RESULTS Significant drug losses were measured (4-38%). Only methods A (crushing-beaker-syringe-water-NGT) and B (crushing-water-syringe-NGT) were suitable for administration of all tested dosage forms. Method B proved the most effective for all kinds of tablets and C/GR (p<0.05) and tended to be more effective also for C/ER (p=0.052) compared to method A. C/P showed minimal losses for both tested methods (B and E). Flushing of the drug through NGT causes major losses during drug administration compared to crushing and transfer (p<0.05). All methods for intact pellets (C-E) were found inappropriate for clinical practice due to NGT clogging. CONCLUSIONS Choosing a suitable administration method can significantly affect the amount of drugs delivered through NGT.

Impact of enteral feeding on gastric tonometry in healthy volunteers and critically ill patients

Background: Enteral feeding may interfere with gastric tonometry measurement. The effect of enteral nutrition on gastric tonometry has not been fully documented.

Determination of Clopidogrel by Chromatography

Clopidogrel, being a potent platelet aggregation inhibitor, is used widely around the world to reduce cardiovas- cular risks in patients with stroke, myocardial infarction, and atherosclerosis. The aim of this review firstly focuses on a comprehensive update of chromatography determination of clopidogrel and its metabolites as well as in human plasma, Wistar rat plasma, and in pharmaceutical preparations. It has been described using TLC, HPLC/MS, RP-HPLC, and GC/MS methods. Secondly to localize the chromatography conditions for separation and quantification, this review pro- vides detailed information on separation conditions for clopidogrel and its metabolites. A new HPLC method adjusted to our laboratory conditions was developed for the evaluation of assay and purity of clopidogrel in film-coated tablets.

Temperature corrected thromboelastography in hypothermia: is it necessary?

Context Hypothermia is known to influence thromboelastography (TEG). TEG reproducibility is generally low. Objective The aim of this study was to evaluate the rationale of TEG temperature adjustment in patients during hypothermia. We hypothesised that temperature adjustment would not be important because of low TEG reproducibility. Design Prospective observational study. Setting Single-centre, secondary care study performed 01/2009 to 07/2010. Patients Survivors of cardiopulmonary resuscitation in whom therapeutic hypothermia (32 to 34°C) was indicated for 24 h were recruited to the study which lasted 36 h. Four hundred samples from 30 patients (22 men and eight women) were obtained. No specific exclusion criteria were defined. Main outcome measures Temperature adjusted and non-adjusted Kaolin–Heparinase and Rapid-TEG were done at 12-h intervals during the first 36 h. Results Bland–Altman plots were used for analysis. During hypothermia, the bias of adjusted measurements was greater in clot formation variables for both Kaolin–Heparinase-TEG (from −15 to −19%) and Rapid-TEG (−9 to −25%) compared to normothermia (from −3 to 3% for Kaolin–Heparinase-TEG and −10 to 2% for Rapid-TEG). Bias of clot strength variables was not influenced by temperature adjustment (median −1%). The 95% limits of agreement were wide for clot formation variables and independent of temperature. In Kaolin–Heparinase-TEG (R −42 to 40% normothermia, −47 to 18% hypothermia) and in Rapid-TEG (R −117 to 97% normothermia, −114 to 95% hypothermia). Limits of agreement of clot strength variables were narrower and independent of temperature in Kaolin–Heparinase-TEG (MA −16 to 13% normothermia, −9 to 10% hypothermia) and also in Rapid-TEG (MA −27 to 24% normothermia, −18 to 20% hypothermia). Conclusion Although TEG analysis with temperature adjusted to the in-vivo value during hypothermia yields results with small systematic bias, the importance of temperature adjustment in clinical routine is low because of the precision limits of TEG measurement itself. Therefore, we see no need to perform TEG analysis at the in-vivo temperature.

Hemophagocytic syndrome in the critically ill.

A case report of a patient with hemophygocytic syndrome - a rare cause of life-threatening pancytopenia in the critical care.