The Effect of Packed Red Blood Cell Transfusion on Cerebral Oxygenation and Metabolism After Subarachnoid Hemorrhage

Background

Anemia adversely affects cerebral oxygenation and metabolism after subarachnoid hemorrhage (SAH) and is also associated with poor outcome. There is limited evidence to support the use of packed red blood cell (PRBC) transfusion to optimize brain homeostasis after SAH. The aim of this study was to investigate the effect of transfusion on cerebral oxygenation and metabolism in patients with SAH.

Methods

This was a prospective observational study in a neurological intensive care unit of a university hospital. Nineteen transfusions were studied in 15 consecutive patients with SAH that underwent multimodality monitoring (intracranial pressure, brain tissue oxygen, and cerebral microdialysis). Data were collected at baseline and for 12 h after transfusion. The relationship between hemoglobin (Hb) change and lactate/pyruvate ratio (LPR) orbrain tissue oxygen (PbtO₂) was tested using univariate and multivariable analyses.

Results

PRBC transfusion was administered on the median post-bleed day 8. The average Hb concentration at baseline was 8.1 g/dL and increased by 2.2 g/dL after transfusion. PbtO₂ increased between hours 2 and 4 post-transfusion and this increase was maintained until hour 10. LPR did not change significantly during the 12-h monitoring period. After adjusting for SpO₂, cerebral perfusion pressure, and LPR, the change in Hb concentration was independently and positively associated with a change in PbtO₂ (adjusted b estimate = 1.39 [95 % confidence interval 0.09–2.69]; P = 0.04). No relationship between the change in Hb concentration and LPR was found.

Conclusions

PRBC transfusion resulted in PbtO₂ improvement without a clear effect on cerebral metabolism prior to SAH.

     

Neuroglucopenia and Metabolic Distress in Two Patients with Viral Meningoencephalitis: A Microdialysis Study

Background

Cerebral edema is a major cause of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Arginine vasopressin (AVP) and water channel aquaporin-4 (AQP4) have been implicated in the pathogenesis of CA-evoked cerebral edema. In this study, we examined if conivaptan, a V_1a and V₂ antagonist, attenuates cerebral edema following CA/CPR in wild type (WT) mice as well as mice with targeted disruption of the gene encoding α-syntrophin (α-syn^?/?) that demonstrate diminished perivascular AQP4 pool.

Methods

Isoflurane-anesthetized adult male WT C57Bl/6 and α-syn^?/? mice were subjected to 8 min CA/CPR and treated with either bolus IV injection (0.15 or 0.3 mg/kg) followed by continuous infusion of conivaptan (0.15 mg/kg/day or 0.3 mg/kg/day), or vehicle infusion for 48 h. Serum osmolality, regional brain water content, and blood–brain barrier (BBB) disruption were determined at the end of the experiment. Sham-operated mice in both strains served as controls.

Results

Treatment with conivaptan elevated serum osmolality in a dose-dependent manner. In WT mice, conivaptan at 0.3 mg dose significantly attenuated regional water content in the caudoputamen (81.0 ± 0.5 vs 82.5 ± 0.4 % in controls; mean ± SEM) and cortex (78.8 ± 0.2 vs 79.4 ± 0.2 % in controls), while conivaptan at 0.15 mg was not effective. In α-syn^?/? mice, conivaptan at 0.3 mg dose did not attenuate water content compared with controls. Conivaptan (0.3 mg/kg/day) attenuated post-CA BBB disruption at 48 h in WT mice but not in α-syn^?/? mice.

Conclusions

Continuous IV infusion of conivaptan attenuates cerebral edema and BBB disruption following CA. These effects of conivaptan that are dependent on the presence of perivascular pool of AQP4 appear be mediated via its dual effect on V₁ and V₂ receptors.

     

Myocardial fatty acid metabolism during acute cardiac allograft rejection

Fatty acids are promptly taken up, metabolised and eliminated by healthy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metabolism. It was the aim of this study to investigate fatty acid metabolism in a rat heart transplant model and to correlate scintigraphic findings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the renal vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-¹²³ jodo-heptadecanoic acid (¹²³J-HDA) with a specific activity of >2×10¹⁷ Bq/ml was scintigraphically measured between days 1 and 11. An increase in the grade of rejection was observed over time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) frames 10–56 were superimposed, time-activity curves generated and monoexponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological examination. The uptake of the tracer identified severe grades of rejection. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did not permit discrimination between grades 1, 2 and 3 a, but significantly decreased in groups 3 b and 4. This method therefore seems to be a valuable tool for the noninvasive detection of severe acute cardiac allograft rejection. Since fatty acid metabolism is clearly stress-dependent it remains to be seen whether this method allows detection of earlier rejection in loaded hearts.     

Risk factors for recurrence of pressure ulcers after defect reconstruction

Patients suffering from pressure ulcers remain to be a challenging task for nursing staff and doctors in the daily clinical management, putting—notably in the case of recurrences—additional strain on the constantly reduced resources in public healthcare. We aimed to assess the risk factors for the recurrence of pressure ulcers at our institution, a tertiary referral center. In this retrospective analysis of patients admitted to our division we identified risk factors for pressure ulcer recurrence. The hospital patient database search included all patients with a diagnosis of pressure ulcers of the torso and lower extremity. One hundred sixty‐three patients were diagnosed with pressure ulcers and 55 patients with 63 pressure ulcers met our inclusion criteria. The 17 recurrences (27%) had an average follow‐up of 728 days. Most presented with lesions of the ischial tuberosity (n=24). Recurrence was statistically associated with defect size (p = 0.013, Cox regression analysis), and serum albumin levels (p = 0.045, Spearman correlation), but no association was found for body mass index, bacterial profile, comorbidities, localization, previous surgery, or time‐to‐admission for reconstruction (all p > 0.05). Supported by the recent literature we identified factors like defect size to be associated with pressure ulcer recurrence, but not with time‐to admission for reconstruction or number of previous debridements. Whether laboratory values like serum albumin levels were the cause, the result or associated with pressure ulcer recurrence warrants further investigation.     

Akutintervention (Primär-PCI) im Rahmen des Essener Herzinfarktverbundes

In a German city (Essen, 490,000 people), a new network system for patients with ST elevation myocardial infarction (STEMI) was established in 2004. This included a so-called integrated care model (IV model) by participation of insurance companies. In a cooperative structure between invasive and noninvasive hospitals, general practitioners and cardiologists as well as emergency systems it could be realized, that every patient with STEMI will be treated by primary percutaneous coronary intervention (PCI) as soon as possible according to the current guidelines. The patient characteristics (age, gender, comorbidity, medication) were comparable to other trials and registries.The primary success rate was high (96.4%). The acute in-hospital results demonstrated a low mortality (7.6%). The time periods of delay were comparable to other registries. The symptom-to-balloon time was 239 min, the medical contact-to-balloon time 95 min, the door-to-balloon time 60 min, and the puncture-to-balloon time 18 min (median values).The STEMI network system in Essen demonstrates the possibility of modern therapy in patients with myocardial infarction (primary PCI) in a cooperative modality between all participants in the health-care system.     

Prognostische Bedeutung der Stressechokardiographie

Appraisal of the risk to which outpatients with chest pain are exposed is an important clinical problem that frequently occurs. The need to decide in day-to-day practice between a conservative or invasive approach in patients with chest pain is often difficult and the decision has grave implications.Stress echocardiography (SE) is readily accessible, the technology is relatively inexpensive, it is familiar and simple to handle, and measurements can be made directly in patients. Even today, its importance has hardly declined at all compared to cardiac MRT or myocardial scintigraphy.Owing to the large number of cases treated, diagnostics and prognostic appraisal of CHD are still a challenge in medical and economic terms. According to the Federal Office of Statistics, a gross expenditure of 6,740 Euros was incurred for every patient > 65 years old in Germany in 2002. 1,650 Euros (24%) was spent on treating diseases of the cardiovascular system.The cumulative data on the prognostic significance of SE indicate a roughly three to four times higher incidence of events in patients with definitive ischemia than in patients in whom ischemia is not detected. Patients with negative SE findings have a very good prognosis and usually do not require invasive diagnostics. Accordingly, consistent use of SE could specifically identify patients in whom a future event will occur and to reduce the number of patients receiving invasive investigations. This selective procedure might reduce health service costs.     

Simultaneous quantitation of metformin and sitagliptin from mouse and human dried blood spots using laser diode thermal desorption tandem mass spectrometry

A simple, rapid and robust high-throughput assay for the simultaneous analysis of metformin and sitagliptin from mouse and human dried blood spot samples using laser diode thermal desorption interfaced with atmospheric pressure chemical ionization tandem mass spectrometry (LDTD-APCI-MS/MS) was developed for use in a pharmaceutical discovery environment as an alternative to traditional plasma analysis. Analytes were extracted from dried blood spots using a simple punch disc and solvent extract procedure. Details of the method development and optimization of the instrumental parameters are presented. The method was successfully applied to spiked mouse and human dried blood spot samples. Analyte stability was determined in dried blood spots on FTA cards and as extracts of dried blood spots. The method was subsequently used to determine the oral pharmacokinetics of metformin and sitagliptin after dosing to male mice. Metformin and Sitagliptin results are compared to data generated by more traditional liquid chromatography-mass spectrometry methods. Intra-assay and inter-assay accuracy and precision across the analytes and species deviated by less than 30% at all calibration levels and less than 20% at all quality control levels.