Karl-Heinz Smolle

Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized clinical trial.

IMPORTANCE Low vitamin D status is linked to increased mortality and morbidity in patients who are critically ill. It is unknown if this association is causal. OBJECTIVE To investigate whether a vitamin D3 treatment regimen intended to restore and maintain normal vitamin D status over 6 months is of health benefit for patients in ICUs. DESIGN, SETTING, AND PARTICIPANTS A randomized double-blind, placebo-controlled, single-center trial, conducted from May 2010 through September 2012 at 5 ICUs that included a medical and surgical population of 492 critically ill adult white patients with vitamin D deficiency (≤20 ng/mL) assigned to receive either vitamin D3 (n = 249) or a placebo (n = 243). INTERVENTIONS Vitamin D3 or placebo was given orally or via nasogastric tube once at a dose of 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months. MAIN OUTCOMES AND MEASURES The primary outcome was hospital length of stay. Secondary outcomes included, among others, length of ICU stay, the percentage of patients with 25-hydroxyvitamin D levels higher than 30 ng/mL at day 7, hospital mortality, and 6-month mortality. A predefined severe vitamin D deficiency (≤12 ng/mL) subgroup analysis was specified before data unblinding and analysis. RESULTS A total of 475 patients were included in the final analysis (237 in the vitamin D3 group and 238 in the placebo group). The median (IQR) length of hospital stay was not significantly different between groups (20.1 days [IQR, 11.1-33.3] for vitamin D3 vs 19.3 days [IQR, 11.1-34.9] for placebo; P = .98). Hospital mortality and 6-month mortality were also not significantly different (hospital mortality: 28.3% [95% CI, 22.6%-34.5%] for vitamin D3 vs 35.3% [95% CI, 29.2%-41.7%] for placebo; hazard ratio [HR], 0.81 [95% CI, 0.58-1.11]; P = .18; 6-month mortality: 35.0% [95% CI, 29.0%-41.5%] for vitamin D3 vs 42.9% [95% CI, 36.5%-49.4%] for placebo; HR, 0.78 [95% CI, 0.58-1.04]; P = .09). For the severe vitamin D deficiency subgroup analysis (n = 200), length of hospital stay was not significantly different between the 2 study groups: 20.1 days (IQR, 12.9-39.1) for vitamin D3 vs 19.0 days (IQR, 11.6-33.8) for placebo. Hospital mortality was significantly lower with 28 deaths among 98 patients (28.6% [95% CI, 19.9%-38.6%]) for vitamin D3 compared with 47 deaths among 102 patients (46.1% [95% CI, 36.2%-56.2%]) for placebo (HR, 0.56 [95% CI, 0.35-0.90], P for interaction = .04), but not 6-month mortality (34.7% [95% CI, 25.4%-45.0%] for vitamin D3 vs 50.0% [95% CI, 39.9%-60.1%] for placebo; HR, 0.60 [95% CI, 0.39-0.93], P for interaction = .12). CONCLUSIONS AND RELEVANCE Among critically ill patients with vitamin D deficiency, administration of high-dose vitamin D3 compared with placebo did not reduce hospital length of stay, hospital mortality, or 6-month mortality. Lower hospital mortality was observed in the severe vitamin D deficiency subgroup, but this finding should be considered hypothesis generating and requires further study. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01130181.

Evaluation of indocyanine green clearance and model for end-stage liver disease for estimation of short-term prognosis in decompensated cirrhosis

Background: Indocyanine green (ICG) clearance has been proposed as a quantitative liver function test several decades ago. Interest in this method has been renewed following the development of finger pulse densitometry for noninvasive estimation of the ICG plasma disappearance rate (PDR). On the other hand, the model for end‐stage liver disease (MELD), which is based on routine laboratory parameters, is widely used for estimation of short‐term survival in cirrhosis, but its prognostic value in critically ill cirrhotic patients is unclear.

IMPACT OF LONG-TERM HEMODIALYSIS ON NUTRITIONAL STATUS IN PATIENTS WITH END-STAGE RENAL FAILURE

We evaluated the way in which duration of hemodialysis treatment affects nutritional status in 96 end-stage renal failure patients. According to the length of previous hemodialysis treatment patients were divided into the groups: onset hemodialysis (ON-HD), early-stage hemodialysis (ES-HD, 1–8 months), mid-stage hemodialysis (MS-HD, 9–69 months), and advanced-stage hemodialysis (ASHD, 70–207 months). Nutritional status was assessed by laboratory data (serum proteins, total lymphocyte count), intradermal skin antigen testing, anthropometric measurements (body mass index [BMI], infrared interactance), and records of food intake. ON-HD patients on a low-protein diet exhibited abnormally low values for serum total protein, albumin, transferrin, and total lymphocyte count and a high prevalence of anergy to skin antigens (69%). In the ES-HD and MS-HD groups values for serum proteins and total lymphocyte count were in the normal range and significantly higher than in ON-HD patients. In addition, a lower proportion of cutaneous anergy was observed (50% and 27%, respectively). Long-term hemodialysis therapy for 6–17 years (AS-HD) was associated with normal levels for all measured serum proteins. Subnormal levels of total lymphocyte count, significantly lower than in MS-HD patients, were associated with an increase in anergy to skin antigens (46%). Serum prealbumin, complement C3c, BMI, body fat, and lean body mass exhibited normal values in all patients and showed no differences between groups. These results indicate that diminished visceral protein stores, lymphopenia, and anergy to skin antigens are widespread in undialyzed uremic patients with end-stage renal failure but become uncommon after the initiation of regular hemodialysis therapy. Even patients on long term hemodialysis for 6–17 years can maintain their serum protein levels, BMI, body fat, and lean body mass in the normal range. The catabolic stimulus of the dialysis procedure itself does not seem to outweigh its beneficial effect of removing uremic toxins when patients are treated for so many years. The occurrence of lymphopenia and a higher proportion of anergy to skin antigens in AS-HD patients indicates that hemodialysis treatment of very long duration has a depressive effect on immunological functions, but not on nutritional status.

Q.E.D. Alcohol Test : A simple and quick method to detect ethanol in saliva of patients in emergency departments : Comparison with the conventional determination in blood

Objective: The aim of this pilot study was to assess whether ethanol concentrations in saliva are comparable to those in blood and to evaluate whether this new non-invasive saliva alcohol test is suitable for use in emergency departments. Design: Prospective, open, non-randomised study. Setting: University hospital emergency department. Patients and methods: 100 consecutive patients who were admitted to the emergency department whose smell and/or behaviour indicated alcohol abuse. Fifteen patients participated as a control group after they were asked to abstain from alcohol consumption for 24 h before the study. Interventions: Blood and saliva samples were obtained at the same time for ethanol measurement. The Q.E.D. Alcohol Test A 350 was used in order to measure the concentration of ethanol in saliva. Blood samples were analysed by the alcohol dehydrogenase method. Results: The mean difference between the ethanol levels in blood and saliva was − 0.1 mg/dl, whereas the values measured in saliva were on average 0.1 mg/dl higher than those measured in blood (p = 0.002). Conclusion: The Q.E.D. Alcohol Test A 350, which uses saliva, is well suited for quantitative determination of alcohol levels. The levels measured in saliva correlate well with those measured in blood at both the lower and the upper end of the scale. Because this test is quick and easy to perform by emergency room personnel and the results are accurate enough for clinical purposes, it should prove valuable to determine whether impaired consciousness is related to alcohol intoxication or to other likely causes.

Efficacy and Safety of Glucose Control with Space GlucoseControl in the Medical Intensive Care Unit—An Open Clinical Investigation

BACKGROUND We aimed to investigate the performance of the Space GlucoseControl system (SGC) (B. Braun, Melsungen, Germany) in medical critically ill patients. The SGC is a nurse-driven, computer-assisted device for glycemic control combining infusion pumps with the enhanced Model Predictive Control algorithm. SUBJECTS AND METHODS The trial was designed as a single-center, open clinical investigation in a nine-bed medical intensive care unit in a tertiary center in Graz, Austria. Efficacy was assessed by percentage of time within the target range (4.4-8.3 mmol/L; primary end point), mean blood glucose, and sampling interval. Safety was assessed by the number of hypoglycemic episodes (≤2.2 mmol/L). RESULTS Twenty mechanically ventilated patients (age, 63±16 years; body mass index, 31.0±10.7 kg/m(2); Acute Physiology and Chronic Health Evaluation II score, 25.4±6.3; 14 males; six with diabetes) were included for a period of 7.0±3.6 days. Time within target range was 83.4±8.9% (mean±SD), and mean arterial blood glucose was 6.8±0.4 mmol/L. No severe hypoglycemic episodes (<2.2 mmol/L) occurred, and the percentage of time within 2.2 and 3.3 mmol/L was low (0.03±0.07%). The sampling interval was 2.0±0.4 h. The mean insulin dose was 93.5±80.1 IU/day, and the adherence to the given insulin dose advice was high (98.3%). A total of 11 unintended therapy interruptions (0.08 events/treatment day) caused by software problems occurred in four patients. CONCLUSIONS SGC is a safe and efficient method to control blood glucose in critically ill patients in the medical intensive care unit.

Hospital Glucose Control: Safe and Reliable Glycemic Control Using Enhanced Model Predictive Control Algorithm in Medical Intensive Care Unit Patients

BACKGROUND The aim of this study was to investigate the performance of the enhanced Model Predictive Control (eMPC) algorithm for glycemic control in medical critically ill patients for the whole length of intensive care unit (ICU) stay. METHODS The trial was designed as a single-center, open, noncontrolled clinical investigation in a nine-bed medical ICU in a tertiary teaching hospital. In 20 patients, blood glucose (BG) was controlled with a laptop-based bedside version of the eMPC. Efficacy was assessed by percentage of time within the target range (4.4-6.1 mM; primary end point), mean BG, and BG sampling interval. Safety was assessed by the number of severe hypoglycemic episodes (<2.2 mM). RESULTS Twenty patients (69 +/- 11 years old; body mass index, 27.4 +/- 4.5 kg/m(2); APACHE II, 25.5 +/- 5.2) were included for a period of 7.3 days (median; interquartile range, 4.4-10.2 days) in the study. Time within target range was 58.12 +/- 10.05% (mean +/- SD). For all patients with at least 7 days in the ICU, there was no statistically significant difference between the daily mean percentage of times in target range in respect of the averages. Mean arterial BG was 5.8 +/- 0.5 mM, insulin requirement was 101.3 +/- 50.7 IU/day, and mean carbohydrate intake (enteral and parenteral nutrition) was 176.4 +/- 61.9 g/day. Three hypoglycemic episodes occurred in three subjects, corresponding to a rate of 0.02 per treatment day. CONCLUSIONS In our single-center, noncontrolled study the eMPC algorithm was a safe and reliable method to control BG in critically medical ICU patients for the whole length of ICU stay.

Comparison of 3 different multianalyte point-of-care devices during clinical routine on a medical intensive care unit

PURPOSE Multianalyte point-of-care (POC) devices are important to guide clinical decisions in critical care. However, the use of different devices in one hospital might cause problems. Therefore, we evaluated 3 commonly used POC devices and analyzed accuracy, reliability, and bias. METHODS Seventy-four arterial blood samples were analyzed by 3 POC devices (Cobas, Roche Diagnostics, Mannheim, Germany; ABL800 Flex, Radiometer GmbH, Germany; Gem Premiere, Instrumentation Laboratory, Germany). For selected parameters, samples were also analyzed in the central laboratory. pCO2, pO2, SO2, bicarbonate and standard bicarbonate, sodium, potassium, calcium, pH, lactate, base excess (BE[B] and BEecf), glucose, hemoglobin, and hematocrit were compared. RESULTS For most parameters, only minor, although statistically significant, changes were observed between the POC devices. For pO2, BE(B), hemoglobin, and hematocrit, clinically significant differences were found. CONCLUSION Although POC devices are of high standard and overall comparability between devices is high, there might be a clinically relevant bias between devices, as found in our study for pO2, BE(B), hemoglobin, and hematocrit. This can be of importance when interpreting results of the same patient obtained from different POC devices, as it could happen when a patient is transferred within a hospital where different devices are used.

Hypoglycaemic coma due to falsely high point-of-care glucose measurements in an ICU-patient with peritoneal dialysis: a critical incidence report

Sir: Hypoglycaemia is a frequent complication in the establishment of tight glycaemic control by means of intensified insulin therapy [1]. Patients in intensive care are often not capable to communicate the presence of hypoglycaemia-associated adverse events and, thus, the reliability and accuracy of glucose measurements are especially important in this environment [2]. Therefore, every attempt should be taken to ensure that point-of-care glucose testing is reliable and technically unavoidable limitations of devices in certain patient groups are well communicated between industry and ICU personnel. In this context, we report a critical incidence due to falsely high pointof-care glucose measurements in a 68-year-old man with a history of diabetes and continuous ambulatory peritoneal dialysis, who was hospitalised for sepsis. In the morning of the first day the patient was increasingly disorientated and dyspnoeic on the ward. Results of an arterial blood gas analysis (Cobas B221, Roche Diagnostics, glucose oxidase method) showed a glucose value of 183 mg/dl. Peritoneal dialysate was exchanged but due to further deterioration of his condition he was admitted to the ICU in the afternoon. At the ICU a capillary glucose value of 496 mg/dl was attained at 19:00 using a bedside glucose meter [Accu-Chek Go, Roche Diagnostics using GDH-PQQ (glucose dehydrogenase pyrroloquinolinequinone test method)]. Despite aggressive insulin administration (*70 IU over 8 h) no accordant decline of glucose was observed (Fig. 1a). At 2:30 in the morning, the patient developed tachyarrhythmia, but this seemed not to disturb his sleep. The nurse in charge suspected hypokalemia following high-dose insulin infusion to be causal for the formation of arrhythmias, she performed an analysis for electrolytes (Cobas B221, Roche Diagnostics). In fact hypokalemia was present (3.2 mmol/l), but more surprisingly a routinely included blood glucose measurement revealed a value of 38 mg/dl, which was in major disagreement to the capillary measurement performed just before (393 mg/dl). At that time the patient was not asleep, but in a hypoglycaemic coma and regained consciousness promptly after glucose administration. On the next day blood samples of the patient were analysed for glucose with commonly used glucose-meters (Fig. 1b). The falsely high glucose values measured with certain devices

Travel-associated rabies in Austrian man.

Rabies developed in an Austrian man after he was bitten by a dog in Agadir, Morocco. Diagnosis was confirmed by reverse transcription–polymerase chain reaction and immunohistochemistry. The patients girlfriend was bitten by the same dog, but she did not become ill.

Near fatal anticholinergic intoxication after routine fundoscopy.

We describe a case of severe anticholinergic intoxication following the topical instillation of tropicamide-containing eyedrops. Tropicamide is a short-acting atropine-like derivative and has been regarded as an effective and safe mydriatic. Half an hour after routine fundoscopy, a 62-year-old man experienced two generalized seizures with respiratory arrest and required intubation and mechanical ventilation. The patient was treated with physostigmine and made a full recovery.