Mean glucose during ICU admission is related to mortality by a U-shaped curve in surgical and medical patients: a retrospective cohort study

Lowering of hyperglycemia in the intensive care unit (ICU) is widely practiced. We investigated in which way glucose regulation, defined as mean glucose concentration during admission, is associated with ICU mortality in a medical and a surgical cohort. Retrospective database cohort study including patients admitted between January 2004 and December 2007 in a 20-bed medical/surgical ICU in a teaching hospital. Hyperglycemia was treated using a computerized algorithm targeting for glucose levels of 4.0-7.0 mmol/l. Five thousand eight hundred twenty-eight patients were eligible for analyses, of whom 1,339 patients had a medical and 4,489 had a surgical admission diagnosis. The cohorts were subdivided in quintiles of increasing mean glucose. We examined the relation between these mean glucose strata and mortality. In both cohorts we observed the highest mortality in the lowest and highest strata. Logistic regression analysis adjusted for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, admission duration and occurrence of severe hypoglycemia showed that in the medical cohort mean glucose levels 8.4 mmol/l and in the surgical cohort mean glucose levels 9.4 mmol/l were associated with significantly increased ICU mortality (OR 2.4-3.0 and 4.9-6.2, respectively). Limitations of the study were its retrospective design and possible incomplete correction for severity of disease. Mean overall glucose during ICU admission is related to mortality by a U-shaped curve in medical and surgical patients. In this cohort of patients a 'safe range' of mean glucose regulation might be defined approximately between 7.0 and 9.0 mmol/

Presence of tobramycin in blood and urine during selective decontamination of the digestive tract in critically ill patients, a prospective cohort study

Tobramycin is one of the components used for selective decontamination of the digestive tract (SDD), applied to prevent colonization and subsequent infections in critically ill patients. Tobramycin is administered in the oropharynx and gastrointestinal tract and is normally not absorbed. However, critical illness may convey gut barrier failure. The aim of the study was to assess the prevalence and amount of tobramycin leakage from the gut into the blood, to quantify tobramycin excretion in urine, and to determine the association of tobramycin leakage with markers of circulation, kidney function and other organ failure. This was a prospective observational cohort study. The setting was the 20-bed closed format-mixed ICU of a teaching hospital. The study population was critically ill patients with an expected stay of more than two days, receiving SDD with tobramycin, polymyxin-E and amphotericin-B four times daily in the oropharynx and stomach. Tobramycin concentration was measured in serum (sensitive high performance liquid chromatography - mass spectrometry/mass spectrometry (HLPC-MS/MS) assay) and 24-hour urine (conventional immunoassay), in 34 patients, 24 hours after ICU admission, and in 71 patients, once daily for 7 days. Tobramycin leakage was defined as tobramycin detected in serum at least once (> 0.05 mg/L). Ototoxicity was not monitored. Of the 100 patients with available blood samples, 83 had tobramycin leakage. Median highest serum concentration for each patient was 0.12 mg/L; 99% of the patients had at least one positive urinary sample (> 0.5 mg/L), 49% had a urinary concentration ≥ 1 mg/L. The highest tobramycin serum concentration was significantly associated with vasopressor support, renal and hepatic dysfunction, and C-reactive protein. At binary logistic regression analysis, high dopamine dose and low urinary output on Day 1 were the significant predictors of tobramycin leakage. Nephrotoxicity could not be shown. The majority of acute critically ill patients treated with enteral tobramycin as a component of SDD had traces of tobramycin in the blood, especially those with severe shock, inflammation and subsequent acute kidney injury, suggesting loss of gut barrier and decreased renal removal. Unexpectedly, urinary tobramycin was above the therapeutic trough level in half of the patients. Nephrotoxicity could not be demonstrated

Does the type of culture medium used influence birthweight of children born after IVF?

STUDY QUESTION: Do culture media influence birthweight of children born after IVF? SUMMARY ANSWER: Some studies have observed a significant effect of culture media on birthweight, while others have not, but since most studies compared different culture media, conventional meta-analysis was not possible. WHAT IS KNOWN ALREADY: Animal studies suggest that in vitro culture of embryos can have a significant effect on the birthweight of offspring when compared with in vivo developed embryos. The type of culture medium (or certain components of the medium) used is one of the causal factors. STUDY DESIGN, SIZE, DURATION: We reviewed all available literature reporting on a relation between culture medium and birthweight in human studies and a selection of animal studies. PARTICIPANTS/MATERIALS, SETTING, METHODS: An extensive literature search on Pubmed and Medline was performed with relevant search criteria relating to IVF, birthweight and culture medium. MAIN RESULTS AND THE ROLE OF CHANCE: Eleven studies reporting on a relationship between culture medium and birthweight in human were included in this review. Five of these found significant differences in birthweight when offspring born after culture in different culture media were compared. The remaining studies did not find differences in birthweight after changing culture medium. LIMITATIONS, REASONS FOR CAUTION: The number of human studies is limited and different culture media with different compositions are compared which makes a comparison between the studies difficult, if not impossible. Furthermore, most study designs were retrospective with consecutive use of different culture media and limited sample sizes, which makes bias of the results likely. WIDER IMPLICATIONS OF THE FINDINGS: If it could be confirmed that the type of culture medium used does indeed influence phenotypic characteristics (such as birthweight) of children born after IVF, it would underline the importance of monitoring the health of IVF children in relation to aspects of the laboratory techniques used during embryo culture

Massive ingestion of cardiac drugs: Toxicokinetic aspects of digoxin and sotalol during hemofiltration

Case. We present the case of a 75-year-old patient admitted to the emergency department after ingesting a large amount of several cardiac drugs, among which were digoxin and sotalol. Because of renal insufficiency, cardiogenic shock, and high serum digoxin levels, the patient received continuous venovenous hemofiltration (CVVH) and digoxin-specific Fab fragments. Digoxin and the digoxin-specific Fab fragments are normally cleared by the kidneys. Methods. Serum-free and total digoxin and serum sotalol concentrations were monitored for several days. Results. Less than 10 of the estimated ingested dose of digoxin was cleared by CVVH within 5 days. Conclusion. CVVH has little influence on the clearance of Fab-bound digoxin from the body. In contrast, sotalol is efficiently cleared by CVVH

Nadroparin versus dalteparin anticoagulation in high-volume, continuous venovenous hemofiltration: A double-blind, randomized, crossover study

Objectives: To compare filter survival times during high-volume, continuous venovenous hemofiltration in patients with normal coagulation variables, using anti-factor Xa bioequivalent doses of nadroparin and dalteparin. To evaluate which other factors influence filter survival time. Design: Randomized, prospective, double-blind, crossover study. Setting: An 18-bed intensive care unit in a 530-bed teaching hospital. Patients: Thirty- two critically ill patients with renal failure, treated with high-volume, continuous venovenous hemofiltration. Interventions: High-volume, postdilutional continuous venovenous hemofiltration, with a standard blood flow rate of 200 mL/min and an ultrafiltrate volume of 100 L in 24 hrs, was performed with a highly permeable, large-surface cellulose triacetate membrane. Anticoagulation with anti-Xa bioequivalent doses of nadroparin and dalteparin was administered in the extracorporeal line before the filter. Blood was sampled for determination of coagulation variables before hemofiltration, 0.5, 2, 4, 6, and 12 hrs after starting the treatment, and at the end of the hemofiltration run. Measurements and Main Results: Anti-Xa peak activity, time of anti-Xa peak activity, area under the curve for 0-3 hrs and filter survival time were not significantly different using nadroparin or dalteparin. When analyzing the patients according to the length of filter survival time, no relationship among anti-Xa peak activity, area under the curve for 0-3 hrs, and filter survival time was found. However, there was a strong trend toward a negative correlation between baseline platelet count and filter survival time (r2 = .11; p = .07). Mean blood urea nitrogen decreased from 81.0 ± 31.9 to 41.1 ± 21.2 mg/dL (p < .01) and mean creatinine decreased from 3.4 ± 1.8 to 1.9 ± 1.2 mg/dL (p < .01). There were no clinically important bleeding complications. Conclusions: Nadroparin and dalteparin are bioequivalent with respect to their anti-Xa activities. Using either drug, we did not find a difference in filter survival time during high-volume, continuous venovenous hemofiltration. No relationship between anti-Xa activity and filter survival time could be found. However, there is a strong trend toward a negative correlation between baseline platelet count and filter survival time. This suggests that during high- volume, continuous venovenous hemofiltration, patients with a higher baseline platelet count might need a different anticoagulation regimen to obtain longer filter survival times

Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial

Objective: To study the effects of the initiation time of continuous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure. The primary end points were mortality at 28 days and recovery of renal function. Design: A randomized, controlled, two-center study. Setting: The closed-format multidisciplinary intensive care units of a university hospital (30 beds) and a teaching hospital (18 beds). Patients and Interventions: A total of 106 ventilated severely ill patients who were oliguric despite massive fluid resuscitation, inotropic support, and high-dose intravenous diuretics were randomized into three groups. Thirty-five patients were treated with early high-volume hemofiltration (72-96 L per 24 hrs), 35 patients with early low-volume hemofiltration (24-36 L per 24 hrs), and 36 patients with late low-volume hemofiltration (24-36 L per 24 hrs). Results: Median ultrafiltrate rate was 48.2 (42.3-58.7) mL·kg-1·hr-1 in early high-volume hemofiltration, 20.1 (17.5-22.0) mL·kg-1·hr-1 in early low-volume hemofiltration, and 19.0 (16.6-21.1) mL·kg-1·hr-1 in late low-volume hemofiltration. Survival at day 28 was 74.3% in early high-volume hemofiltration, 68.8% in early low-volume hemofiltration, and 75.0% in late low-volume hemofiltration (p = .80). On average, hemofiltration started 7 hrs after inclusion in the early groups and 42 hrs after inclusion in the late group. All hospital survivors had recovery of renal function at hospital discharge, except for one patient in the early low-volume hemofiltration group. Median duration of renal failure in hospital survivors was 4.3 (1.4-7.8) days in early high-volume hemofiltration, 3.2 (2.4-5.4) days in early low-volume hemofiltration, and 5.6 (3.1-8.5) days in late low-volume hemofiltration (p = .25). Conclusions: In the present study of critically ill patients with oliguric acute renal failure, survival at 28 days and recovery of renal function were not improved using high ultrafiltrate volumes or early initiation of hemofiltration

Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial

Objective. To study the effects of the initiation time of continuous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure. The primary end points were mortality at 28 days and recovery of renal function. Design: A randomized, controlled, two-center study. Setting: The closed-format multidisciplinary intensive care units of a university hospital (30 beds) and a teaching hospital (18 beds). Patients and Interventions. A total of 106 ventilated severely ill patients who were oliguric despite Passive fluid resuscitation, inotropic support, and high-dose intravenous diuretics were randomized into three groups. Thirty-five patients were treated with early high-volume hemofiltration (72-96 L per 24 hrs), 35 patients with early low-volume hemofiltration (24-36 L per 24 hrs), and 36 patients with late low-volume hemofiltration (24-36 L per 24 hrs). Results. Median ultrafiltrate rate was 48.2 (42.3-58.7) mL(.)kg(-1.)hr(-1) in early high-volume hemofiltration, 20.1 (17.5-22.0) mL.kg(-1.)hr(-1) in early low-volume hemofiltration, and 19.0 (16.6-21.1) mL(.)kg(-1.)hr(-1) in late low-volume hemofiltration. Survival at day 28 was 74.3% in early high-volume hemofiltration, 68.8% in early low-volume hemofiltration, and 75.0% in late low-volume hemofiltration (p = .80). On. average, hemofiltration started 7 hrs after inclusion in the early groups and 42 hrs after inclusion in the late group. All hospital survivors had recovery of renal function at hospital discharge, except for one patient in the early low-volume hemofiltration group. Median duration of renal failure in hospital survivors was 4.3 (1.4-7.8) days in early high-volume hemofiltration, 3.2 (2.4-5.4) days in early low-volume hemofiltration, and 5.6 (3.1-8.5) days in late low-volume hemofiltration (p = .25). Conclusions: In the present study of critically ill patients with oliguric acute renal failure, survival at 28 days and recovery of renal function were not improved using high ultrafiltrate volumes or early initiation of hemofiltratio