Reinhard Kitzberger

Real-Time Continuous Glucose Monitoring in Critically Ill Patients: A prospective randomized trial

OBJECTIVE To evaluate the impact of real-time continuous glucose monitoring (CGM) on glycemic control and risk of hypoglycemia in critically ill patients. RESEARCH DESIGN AND METHODS A total 124 patients receiving mechanical ventilation were randomly assigned to the real-time CGM group (n = 63; glucose values given every 5 min) or to the control group (n = 61; selective arterial glucose measurements according to an algorithm; simultaneously blinded CGM) for 72 h. Insulin infusion rates were guided according to the same algorithm in both groups. The primary end point was percentage of time at a glucose level <110 mg/dl. Secondary end points were mean glucose levels and rate of severe hypoglycemia (<40 mg/dl). RESULTS Percentage of time at a glucose level <110 mg/dl (59.0 ± 20 vs. 55.0 ± 18% in the control group, P = 0.245) and the mean glucose level (106 ± 18 vs. 111 ± 10 mg/dl in the control group, P = 0.076) could not be improved using real-time CGM. The rate of severe hypoglycemia was lower in the real-time CGM group (1.6 vs. 11.5% in the control group, P = 0.031). CGM reduced the absolute risk of severe hypoglycemia by 9.9% (95% CI 1.2–18.6) with a number needed to treat of 10.1 (95% CI 5.4–83.3). CONCLUSIONS In critically ill patients, real-time CGM reduces hypoglycemic events but does not improve glycemic control compared with intensive insulin therapy guided by an algorithm.

Accuracy and reliability of a subcutaneous continuous glucose-monitoring system in critically ill patients.

Background:Continuous glucose monitoring has been proposed to optimize glucose control in critically ill patients. To achieve strict glucose regulation, accurate and reliable continuous glucose-monitoring systems are essential. Objective:Evaluation of a subcutaneous continuous glucose-monitoring system for use in critically ill patients. Design:Pooled-data analysis of two prospective, randomized, controlled trials. Setting:An eight-bed medical intensive care unit of a university hospital. Patients:A total of 174 critically ill patients on intensive insulin therapy. Interventions:Subcutaneous continuous glucose monitoring. Measurements:Two thousand forty-five continuous glucose-monitoring system sensor glucose values were compared with arterial reference blood glucose levels, determined by a blood gas analyzer. Continuous glucose monitoring data were recorded continuously for up to 72 hrs by using a subcutaneous continuous glucose-monitoring sensor. The correlation of both methods and differences between continuous glucose-monitoring systems and reference values were calculated, as well as the conformity of continuous glucose-monitoring values with the International Organization for Standardization criteria (<0.83 mmol/L [15 mg/dL] difference for glucose values ≤4.12 mmol/L [≤75 mg/dL] and <20% difference for glucose values >4.12 mmol/L [>75 mg/dL]). Results:The Pearson correlation coefficient was 0.92, showing strong correlation between the two methods. The intraclass correlation coefficient was 0.92, indicating that 92% of the variability is due to subjects and measurement occasions. Mean difference between continuous glucose-monitoring system and reference values was −0.10 mmol/L (confidence interval: −0.13 to −0.07) (−2 mg/dL [confidence interval: −2 to −1]) (continuous glucose-monitoring system minus reference) and absolute difference 0.44 mmol/L (confidence interval: 0.41–0.47) (8 mg/dL [confidence interval: 7–8]). According to the insulin titration error grid analysis, 99.1% of continuous glucose-monitoring system values were in the acceptable treatment zone. No continuous glucose-monitoring system measurements were found in the life-threatening zone, and 92.9% of the continuous glucose-monitoring system glucose values met the International Organization for Standardization criteria. Conclusion:The subcutaneous continuous glucose-monitoring system is reliable for use in critically ill patients and showed glucose values with a strong correlation to arterial reference blood glucose levels, determined by a blood gas analyzer.

Jejunal tube placement in critically ill patients: A prospective, randomized trial comparing the endoscopic technique with the electromagnetically visualized method.

Objective:Head-to-head comparison of the success rate of jejunal placement of a new electromagnetically visualized jejunal tube with that of the endoscopic technique in critically ill patients. Design:Prospective, randomized clinical trial. Setting:Two intensive care units at a university hospital. Patients:A total of 66 critically ill patients not tolerating intragastric nutrition. Interventions:Patients were randomly assigned (2:1 ratio) to receive an electromagnetically visualized jejunal feeding tube or an endoscopically placed jejunal tube. The success rate of correct jejunal placement after 24 hrs was the main outcome parameter. Measurements and Main Results:The correct jejunal tube position was reached in 21 of 22 patients using the endoscopic technique and in 40 of 44 patients using the electromagnetically visualized jejunal tube (95% vs. 91%; relative risk 0.9524, confidence interval 0.804–1.127, p = .571). In the remaining four patients, successful endoscopic jejunal tube placement was performed subsequently. The implantation times, times in the right position, and occurrences of nose bleeding were not different between the two groups. The electromagnetically visualized technique resulted in the correct jejunal position more often at the first attempt. Factors associated with successful placement at the first attempt of the electromagnetically visualized jejunal tube seem to be a higher body mass index and absence of emesis. This trial is registered at ClinicalTrials.gov, number NCT00500851. Conclusions:In a head-to-head comparison correct jejunal tube placement using the new electromagnetically visualized method was as fast, safe, and successful as the endoscopic method in a comparative intensive care unit patient population.

Correlation of calculated indices of insulin resistance (QUICKI and HOMA) with the euglycaemic hyperinsulinaemic clamp technique for evaluating insulin resistance in critically ill patients

Background and objective: Insulin resistance is frequently observed in critical illness. It can be quantified by the expensive and time‐consuming euglycaemic hyperinsulinaemic clamp technique (M‐value) and calculated indices of insulin resistance (Quantitative Insulin Sensitivity Check Index; QUICKI and Homeostasis Model Assessment; HOMA) with lower costs and efforts. We performed an observational study to assess the reliability of QUICKI and HOMA to evaluate insulin resistance in critically ill patients compared with the current gold standard method, the euglycaemic hyperinsulinaemic clamp technique. Methods: Insulin resistance was measured in 30 critically ill medical patients by the euglycaemic hyperinsulinaemic clamp technique (M‐value) as well as calculated using QUICKI and HOMA. Correlations between the M‐values as well as QUICKI and HOMA were assessed by means of the Pearsons correlation coefficient. Results: M‐value, QUICKI and HOMA indicated insulin resistance in all 30 patients. However, both indices QUICKI and HOMA did not correlate with the M‐values in our patients (r2 = 0.008 and 0.0005, respectively). A significant negative correlation was found between the M‐value and the severity of illness assessed by the APACHE (Acute Physiology and Chronic Health Evaluation) III score (r2 = 0.16; P < 0.05). In contrast, neither HOMA nor QUICKI correlated with the APACHE III score (r2 = 0.034 and 0.033, respectively). Conclusions: Although QUICKI and HOMA indicated insulin resistance in the critically ill medical patients, both indices did not correlate with the M‐value. Therefore, the euglycaemic hyperinsulinaemic clamp technique remains the gold standard for estimating insulin resistance in critically ill patients.

Early treatment with IgM-enriched intravenous immunoglobulin does not mitigate critical illness polyneuropathy and/or myopathy in patients with multiple organ failure and SIRS/sepsis: a prospective, randomized, placebo-controlled, double-blinded trial

IntroductionCritical illness polyneuropathy and/or myopathy (CIPNM) is a severe complication of critical illness. Retrospective data suggest that early application of IgM-enriched intravenous immunoglobulin (IVIG) may prevent or mitigate CIPNM. Therefore, the primary objective was to assess the effect of early IgM-enriched IVIG versus placebo to mitigate CIPNM in a prospective setting.MethodsIn this prospective, randomized, double-blinded and placebo-controlled trial, 38 critically ill patients with multiple organ failure (MOF), systemic inflammatory response syndrome (SIRS)/sepsis, and early clinical signs of CIPNM were included. Patients were randomly assigned to be treated either with IgM-enriched IVIG or placebo over a period of three days. CIPNM was measured by the CIPNM severity sum score based on electrophysiological stimulation of the median, ulnar, and tibial nerves on days 0, 4, 7, 14 and on the histological evaluation of muscle biopsies on days 0 and 14 and ranged from 0 (no CIPNM) to 8 (very severe CIPNM).ResultsA total of 38 critically ill patients were included and randomized to receive either IgM-enriched IVIG (n = 19) or placebo (n = 19). Baseline characteristics were similar between the two groups. CIPNM could not be improved by IVIG treatment, represented by similar CIPNM severity sum scores on day 14 (IVIG vs. placebo: 4.8 ± 2.0 vs. 4.5 ± 1.8; P = 0.70). CIPNM severity sum score significantly increased from baseline to day 14 (3.5 ± 1.6 vs. 4.6 ± 1.9; P = 0.002). After an interim analysis the study was terminated early due to futility in reaching the primary endpoint.ConclusionsEarly treatment with IVIG did not mitigate CIPNM in critically ill patients with MOF and SIRS/sepsis.Trial registrationClinicaltrials.gov: NCT01867645

Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

ABSTRACT Ganciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

Stress-Hyperglykämie – Einfluss auf Morbidität und Mortalität beim Akutpatienten

Die Stress-Hyperglykämie wurde bereits vor 130 Jahren von Claude Bernard in seinen Beobachtungen beim Blutungsschock erstmals ausführlich beschrieben [1]. Bis vor wenigen Jahren waren wir der Meinung, dass bei Intensivpatienten diese Stress-Hyperglykämie als adaptives Epiphänomen im Sinne einer physiologischen Gegenregulation zu akzeptieren ist und Blutzuckerwerte um 200 mg/dl sogar positive Effekte auf den Stoffwechsel des Intensivpatienten haben. Zu diesem gestörten Glukosestoffwechsel kommt es bei akuten Erkrankungen unabhängig von vorbestehenden Glukosestoffwechsel-Erkrankungen wie Diabetes mellitus. Dabei spielt die periphere Insulinresistenz, die durch eine Hyperinsulinämie, eine beeinträchtigte periphere Insulin-mediierte Glukoseaufnahme ins Muskelgewebe und eine gleichzeitig erhöhte hepatische Glukoneogenese charakterisiert ist, die zentrale Rolle [2]. Zahlreiche klinische Studien zeigen jedoch, dass diese Stress-Hyperglykämie nicht nur ein Epiphänomen darstellt, sondern negative Auswirkungen auf Morbidität und Mortalität aufweisen. Eine rezente Untersuchung bei 6187 Patienten auf einer Notfallaufnahme in Australien zeigte eindrucksvoll, dass der Blutzuckerwert bei der Aufnahme ein unabhängiger Prädiktor für die Mortalität darstellt [3]. Je höher der Blutzuckerspiegel war, umso höher war die Mortalität. Pro Anstieg des Blutzuckerspiegels um 1 mmol/l stieg die Hasard-Ratio zu versterben signifikant um 1,04 an. Auffallend war aber vor allem, dass dieser Zusammenhang nur bei jenen Patienten bestand, die keinen vorbestehenden Diabetes mellitus hatten, nicht jedoch bei jenen Patienten mit bekanntem Diabetes mellitus. Auch für spezielle Krankheitsbilder konnten ähnliche Zusammenhänge zwischen Blutzuckerspiegel und Morbidität beziehungsweise Mortalität gezeigt werden. Eine Metaanalyse ergab für den akuten Myokardinfarkt eine sehr enge Korrelation zwischen dem Ausmaß der StressHyperglykämie und der Entwicklung eines kardiogenen Schock, Herzversagens und erhöhter Spitalsmortalität [4]. Auch bei kardiochirurgischen Patienten ist eine perioperative Hyperglykämie mit einer erhöhten Mortalität assoziiert [5]. Ähnliche Ergebnisse zeigen sich auch bei Trauma-Patienten, bei denen die Hyperglykämie mit einer erhöhten Mortalität, verlängerter Liegedauer und erhöhter Infektionsrate assoziiert ist [6]. Auch bei Schlaganfallpatienten bewirkt eine Hyperglykämie ein höheres Risiko zu versterben und bei jenen Patienten, die überleben, ist die neurologische Rehabilitation umso schlechter, je ausgeprägter in der Akutphase die Hyperglykämie war [7]. In dieser Ausgabe der Wiener Klinischen Wochenschrift wird nun erstmals der Zusammenhang zwischen Vorhofflimmern bei akutem Myokardinfarkt und einer Stress-Hyperglykämie beschrieben [8]. Die Autoren führten eine retrospektive Analyse bei 543 Patienten mit akutem Myokardinfarkt durch und zeigten eindrucksvoll, dass eine Stress-Hyperglykämie mit einer erhöhten Prävalenz von Vorhofflimmern assoziiert ist. Jene Patientengruppe mit einer Stress-Hyperglykämie über 8 mmol/l und Vorhofflimmern hatten eine 14.5 fach höhere Spitalsmortalität als jene Patientengruppe ohne Stress-Hyperglykämie und Vorhofflimmern. Während eine Stress-Hyperglykämie in einer multivariaten Regressionsanalyse ein unabhängiger Prädiktor für eine erhöhte Mortalität war, stellte hingegen Vorhofflimmern keinen unabhängigen Risikofaktor dar. Diese Ergebnisse werfen drei wichtige Fragen auf: