Local metabolic changes in subcutaneous adipose tissue during intravenous and epidural analgesia.

BACKGROUND: This clinical study aimed at investigating the impact of postoperative thoracic epidural analgesia on extracellular glycerol concentration and glucose metabolism in subcutaneous adipose tissue, using the microdialysis technique. The sympathetic nervous activity, which can be attenuated by epidural anesthesia, influences lipolysis and the release of glycerol. METHODS: Fourteen patients who underwent major abdominal or thoraco-abdominal surgery were studied postoperatively over 3 days. For postoperative analgesia the patients were prospectively randomized to receive either thoracic epidural analgesia with a bupivacaine/morphine infusion (EPI-group, n=6) or a continuous i.v. infusion of morphine (MO-group, n=8). The concentration of glycerol, glucose and lactate in the abdominal and deltoid subcutaneous adipose tissue were measured using a microdialysis technique. RESULTS: The abdominal glycerol levels were equal in both groups. In the deltoid region of the EPI-group, glycerol concentrations started to increase on Day 2, and reached significantly higher levels on Day 3 compared with the MO-group. The glucose and lactate levels showed no differences between groups in the two regions. CONCLUSION: The uniform glycerol levels in abdominal subcutaneous adipose tissue in conjunction with the difference in glycerol levels in the deltoid area indicate that the local lipolysis is different in the two study groups. This might be explained by a regional metabolic influence of thoracic epidural analgesia, possibly via the sympathetic nervous system

Anaesthesia and PET of the Brain

Although drugs have been used to administer general anaesthesia for more than a century and a half, relatively little was known until recently about the molecular and cellular effects of the anaesthetic agents and the neurobiology of anaesthesia. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have played a valuable role in improving this knowledge. PET studies using 11C-flumazenil binding have been used to demonstrate that the molecular action of some, but not all, of the current anaesthetic agents is mediated via the GABAA receptor. Using different tracers labelled with 18F, 11C and 15O, PET studies have shown the patterns of changes in cerebral metabolism and blood flow associated with different intravenous and volatile anaesthetic agents. Within classes of volatile agents, there are minor variations in patterns. More profound differences are found between classes of agents. Interestingly, all agents cause alterations in the blood flow and metabolism of the thalamus, providing strong support for the hypothesis that the anaesthetic agents interfere with consciousness by interfering with thalamocortical communication.</p

ICP curve morphology and intracranial flow-volume changes: a simultaneous ICP and cine phase contrast MRI study in humans

Background: The intracranial pressure (ICP) curve with its different peaks has been extensively studied, but the exact physiological mechanisms behind its morphology are still not fully understood. Both intracranial volume change (ΔICV) and transmission of the arterial blood pressure have been proposed to shape the ICP curve. This study tested the hypothesis that the ICP curve correlates to intracranial volume changes. Methods: Cine phase contrast magnetic resonance imaging (MRI) examinations were performed in neuro-intensive care patients with simultaneous ICP monitoring. The MRI was set to examine cerebral arterial inflow and venous cerebral outflow as well as flow of cerebrospinal fluid over the foramen magnum. The difference in total flow into and out from the cranial cavity (Flowtot) over time provides the ΔICV. The ICP curve was compared to the Flowtot and the ΔICV. Correlations were calculated through linear and logarithmic regression. Student’s t test was used to test the null hypothesis between paired samples. Results: Excluding the initial ICP wave, P1, the mean R2 for the correlation between the ΔICV and the ICP was 0.75 for the exponential expression, which had a higher correlation than the linear (p = 0.005). The first ICP peaks correlated to the initial peaks of Flowtot with a mean R2 = 0.88. Conclusion: The first part, or the P1, of the ICP curve seems to be created by the first rapid net inflow seen in Flowtot while the rest of the ICP curve seem to correlate to the ΔICV

Analyses of cerebral microdialysis in patients with traumatic brain injury: relations to intracranial pressure, cerebral perfusion pressure and catheter placement

<p>Abstract</p> <p>Background</p> <p>Cerebral microdialysis (MD) is used to monitor local brain chemistry of patients with traumatic brain injury (TBI). Despite an extensive literature on cerebral MD in the clinical setting, it remains unclear how individual levels of real-time MD data are to be interpreted. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are important continuous brain monitors in neurointensive care. They are used as surrogate monitors of cerebral blood flow and have an established relation to outcome. The purpose of this study was to investigate the relations between MD parameters and ICP and/or CPP in patients with TBI.</p> <p>Methods</p> <p>Cerebral MD, ICP and CPP were monitored in 90 patients with TBI. Data were extensively analyzed, using over 7,350 samples of complete (hourly) MD data sets (glucose, lactate, pyruvate and glycerol) to seek representations of ICP, CPP and MD that were best correlated. MD catheter positions were located on computed tomography scans as pericontusional or nonpericontusional. MD markers were analyzed for correlations to ICP and CPP using time series regression analysis, mixed effects models and nonlinear (artificial neural networks) computer-based pattern recognition methods.</p> <p>Results</p> <p>Despite much data indicating highly perturbed metabolism, MD shows weak correlations to ICP and CPP. In contrast, the autocorrelation of MD is high for all markers, even at up to 30 future hours. Consequently, subject identity alone explains 52% to 75% of MD marker variance. This indicates that the dominant metabolic processes monitored with MD are long-term, spanning days or longer. In comparison, short-term (differenced or Δ) changes of MD vs. CPP are significantly correlated in pericontusional locations, but with less than 1% explained variance. Moreover, CPP and ICP were significantly related to outcome based on Glasgow Outcome Scale scores, while no significant relations were found between outcome and MD.</p> <p>Conclusions</p> <p>The multitude of highly perturbed local chemistry seen with MD in patients with TBI predominately represents long-term metabolic patterns and is weakly correlated to ICP and CPP. This suggests that disturbances other than pressure and/or flow have a dominant influence on MD levels in patients with TBI.</p

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants

One way to ventilate patients during fibreoptic intubation

Occasionally anaesthesiologists find themselves in situations where ventilation during intubation with a fibreoptic bronchoscope (FOB) is desirable. In order to ventilate the patient during the FOB intubation, we used a 90 degree angle swivel connector, normally used for fibreoptic bronchoscopia in an intubated patient. After a nasotracheal tube is placed with the tip in the oropharynx, ventilation of the patient is possible via this tube by closing the mouth and other nostril. The fibrescopic procedure is done through the right-angle connector with suction port and the tube is used to guide the tip of the FOB to the aditus laryngis. The method has been used in 7 patients who were impossible to intubate with a conventional procedure. In all patients ventilation was possible and intubation was performed in 5 min (range 1-15)