Cerebral Microdialysis in Aneurismal Subarachnoid Hemorrhage Patient Reveals a Detrimental Shift in Brain Energy Metabolism, Despite Normal Perfusion Pressure.

The present case study concerns a patient admitted to our neuro-intensive care unit with a severe aneurismal subarachnoid hemorrhage rebleeding. The patient was equipped with multimodal neuromonitoring, including cerebral microdialysis. During the neuro-intensive care unit, there was a gradual decrease in cerebral perfusion pressure, which was within normally accepted levels, correlated to a detrimental shift in cerebral metabolism, from mitochondrial dysfunction to an ischemic pattern. Subsequently, the clinical and paraclinical status of the patient worsened. The present case highlights how the dynamic assessment of cerebral metabolic patterns and the concept of mitochondrial dysfunction can be relevant in the day-to-day clinical setting, to evaluate and optimize basic, well-known physiological parameters, such as cerebral perfusion pressure.

[Very low cerebral glucose level despite normal systemic glucose level in a patient with subarachnoid haemorrhage].

In this case report, data are presented from a patient, who suffered from a severe subarachnoid haemorrhage and was admitted to the neuro-intensive care unit, where the use of cerebral microdialysis (CMD) allowed the detection of a severe mismatch between cerebral and systemic glucose levels and compromised cerebral metabolism despite systemic glucose values within the normal range. The established CMD monitoring allowed subsequent titration of insulin respecting acceptable cerebral and systemic glucose levels.

Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.

BACKGROUND: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS: In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS: A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS: Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).

Decision support for optimized blood glucose control and nutrition in a neurotrauma intensive care unit: preliminary results of clinical advice and prediction accuracy of the Glucosafe system.

Assessment of glycemic control with model-based decision support ("Glucosafe") in neurotrauma intensive care patients in an ongoing randomized controlled trial with a blood glucose (BG) target of 5-8 mmol/L. Assessment of BG prediction accuracy of the model and assessment of the effect that two potential model extensions would have on prediction accuracy in this trial. In the intervention group insulin infusion rates and nutrition are varied based on Glucosafe's decision support. In the control group, the caloric target is 25-30 kcal/kg per day and insulin is regulated according to department rules. BG concentrations, insulin infusion rates, and feed rates are compared from the data of 12 consecutive patients. BG measurements are predicted retrospectively and the mean relative prediction error is calculated using (1) the current model from the trial, (2) the current model modified by using a BG-dependent variable endogenous insulin appearance rate, (3) the current model modified by a patient-specific carbohydrate absorption factor. BG control was improved by Glucosafe. 76 % of BG measurements in Glucosafe patients were in the 5-8 mmol/L band (Controls: 51 %). BG means (log-normal) ± SD were 7.0 ± 1.19 mmol/L in Glucosafe patients compared to 8.0 ± 1.24 mmol/L in controls (P = 0.05). Mean caloric intake was 93.5 ± 15 % of resting energy expenditure in Glucosafe patients (Controls: 129 ± 29 %). The BG-dependent variable insulin appearance rate had no measurable effect on prediction accuracy. The patient-specific carbohydrate absorption factor improved prediction accuracy significantly (P = 0.001). Glucosafe advice reduces hyperglycemia in neurotrauma intensive care patients. Further parameterization can improve model prediction accuracy.

A simulation model of insulin saturation and glucose balance for glycemic control in ICU patients.

Consistent tight blood sugar control in critically ill patients has proven elusive. Properly accounting for the saturation of insulin action and reducing the need for frequent measurements are important aspects in intensive insulin therapy. This paper presents a composite metabolic model, 'Glucosafe', that integrates models and parameters from normal physiology and accounts for the reduced rate of glucose gut absorption and saturation of insulin action in patients with reduced insulin sensitivity. Particularly, two different sites of reduced insulin sensitivity, before and after the non-linearity of insulin action, are explored with this model. These approaches are assessed based on the model's accuracy in retrospectively predicting blood glucose measurements of 10 randomly chosen, hyperglycemic intensive care patients. For each patient, median absolute percent error is <25% for prediction times < or = 270min and modelling reduced insulin sensitivity after the non-linearity, compared to <29% for modelling reduced insulin sensitivity before the non-linearity. Scaling the insulin effect (after the non-linearity) is a suitable assumption in this model structure. These results are preliminary and subject to further and more extensive validation of the model's capability to predict the longer term (>2h) blood glucose excursion in critically ill patients.

The Glucosafe system for tight glycemic control in critical care: a pilot evaluation study.

PURPOSE: "Glucosafe' is a new model-based decision support system for glycemic control in critical care. Safety and achievement of glycemic goals using the system are tested prospectively. METHODS: Four penalty functions were developed to balance regimens of nutrition and insulin therapy against model-predicted glycemic outcome. The system advises the regimen where the penalty sum is minimal. An interactive interface allows advice alterations. Ten hyperglycemic patients (median Acute Physiology and Chronic Health Evaluation II, 12.5; interquartile range, 7.5-16.3) from a neuro and trauma intensive care unit were included for pilot testing using Glucosafe for 12 to 14 hours. Glycemic outcomes were compared to the 24-hour intervals before and after intervention. RESULTS: Hypoglycemia (blood glucose [BG] <3.5 mmol/L) was not observed. Mean log-normal BG +/- standard deviation was reduced from 8.6 +/- 2.4 mmol/L preintervention to 7.0 +/- 1.1 mmol/L during the intervention. Nine patients reached the 4.4- to 6.1-mmol/L band after a mean 5 hours. At 5 hours intervention, mean log-normal BG was 6.7 mmol/L, 40% of measurements were in the 4.4- to 6.1-mmol/L band, and 84% were in the 4.4- to 7.75-mmol/L band. CONCLUSIONS: Safety was demonstrated with the developed penalty functions. The low BG variance achieved may permit minor adjustments of the penalty function values to reduce average BG if desired.

The ICP-lowering effect of 10 degrees reverse Trendelenburg position during craniotomy is stable during a 10-minute period.

Recently we studied the effect of 10 degrees reverse Trendelenburg position on subdural pressure and cerebral perfusion pressure (CPP) during craniotomy. Within 1 minute we found a significant decrease in subdural pressure while CPP was unchanged. A longer time span, however, is necessary to exclude a temporary effect. In the present investigation we studied subdural pressure, CPP, and jugular bulb pressure (JBP) before and during a 10-minute period after change in position. Fifteen patients with supratentorial cerebral tumors were anesthetized with propofol/fentanyl in the supine position. Mean arterial blood pressure and JBP were measured invasively, and subdural pressure was measured after removal of the bone flap. End-tidal CO2, PaCO2, PaO2, heart rate, jugular venous oxygen saturation (SjO2), and arteriovenous oxygen difference (AVDO2) were also measured. Dural tension was estimated by the surgeon. The measurements were performed with the patients in a neutral position and during a 10-minute period after positioning the patient in a 10 degrees reverse Trendelenburg position. After 1 minute in the reverse Trendelenburg position, the mean value of subdural pressure decreased from 10.9 +/- 5.7 to 7.3 +/- 5.2 mm Hg (P<0.05) and remained unchanged for the following 9 minutes. Correspondingly, dural tension was lessened significantly. Jugular pressure and mean arterial blood pressure decreased significantly as well (P<0.05), but the CPP was unaffected. No significant changes in PaCO2, PaO2, end-tidal CO2, heart rate, SjO2, or AVDO2 were disclosed. During craniotomy 10 degrees reverse Trendelenburg position reduces subdural pressure and dural tension within 1 minute without reducing CPP. During the following 9 minutes the levels of subdural pressure and CPP are unchanged.

Reverse Trendelenburg position reduces intracranial pressure during craniotomy.

Cerebral swelling and herniation pose serious surgical obstacles during craniotomy for space-occupying lesions. Positioning patients head-up has been shown previously to reduce intracranial pressure (ICP) in neurotraumatized patients, but has not been investigated during intracranial surgery. The current study examined the effects of 10-deg reverse Trendelenburg position (RTP) on ICP and cerebral perfusion pressure (CPP). Forty adult patients subjected to craniotomy for supratentorial tumors were given standardized propofol-fentanyl-cisatracurium general anesthesia and were moderately hyperventilated. In 26 of 40 patients with expected poor clinical outcome, an additional catheter was placed in the internal jugular bulb to determine internal jugular bulb pressure (JBP). ICP was determined by subdural measurement using a 22-gauge needle advanced through the dura after removal of the bone flap. ICP was referenced to the level of the dural incision. ICP, mean arterial blood pressure, and CPP were compared with repeat measurements 1 minute after RTP. The tension of the dura was graded qualitatively by the surgeon by digital palpation and was compared to post-RTP. ICP decreased from 9.5 mm Hg to 6.0 mm Hg ( P <.001; all values are median) within 1 minute after 10-deg RTP. Mean arterial blood pressure decreased from 82.0 mm Hg to 78.5 mm Hg ( P <.001). CPP was unchanged (70.5 mm Hg versus 71 mm Hg after RTP), whereas JBP decreased from 8 mm Hg to 4 mm Hg ( P <.001). High initial ICP was correlated to the greatest magnitude of decrease in ICP. No significant correlation was found between change in ICP and change in JBP. Intracranial pressure after RTP resulted in decreased tension of the dura. RTP appears to be an effective means of reducing ICP during craniotomy, thereby reducing the risk of cerebral herniation. CPP is not affected. Studies over longer periods of time are warranted, however.