Peter Frykholm

Increase of interstitial glycerol reflects the degree of ischaemic brain damage: a PET and microdialysis study in a middle cerebral artery occlusion-reperfusion primate model.

OBJECTIVE To evaluate interstitial glycerol as a marker of ischaemia by studying the changes in glycerol in direct relation to changes in regional cerebral metabolic rate of oxygen (CMRO2), the lactate/pyruvate ratio (LP ratio), and glutamate. METHODS Transorbital 2 hour middle cerebral artery occlusion (MCAO) was performed in eight monkeys, which were studied with continuous microdialysis for 24 hours. Interstitial fluids were collected by microdialysis and analysed for glycerol, lactate, pyruvate, and glutamate with an enzymatic assay and high performance liquid chromatography. Sequential PET studies of cerebral blood flow (CBF), CMRO2, oxygen extraction ratio (OER), and cerebral blood volume (CBV) were performed. The microdialysis probe regions were classified as severe ischaemia or penumbra, depending on whether the mean CMRO2 side to side ratio was below or above 60%, respectively. RESULTS A nine-fold, sustained increase in glycerol was registered after MCAO in severe ischaemia regions. In penumbra regions, the increase in glycerol was five-fold, but the glycerol concentration returned to baseline within 8 hours of clip removal. The difference between severe ischaemia and penumbra glycerol values was statistically significant. As expected from previous studies, the interstitial LP ratio and glutamate increased markedly in severe ischaemia, with a less pronounced change in penumbra regions. There was a time lag between the biochemical changes in severe ischaemia regions, with the LP ratio preceding glutamate, followed by glycerol. CONCLUSIONS A marked, sustained increase in interstitial glycerol is indicative of severe ischaemia in this stroke model. A transient, diminutive increase in interstitial glycerol may reflect a penumbra situation. Interstitial glycerol in combination with other biochemical markers such as the LP ratio and glutamate may be useful for clinical monitoring of the ischaemic brain, reflecting a sequence of secondary pathophysiological events.

Middle Cerebral Artery Occlusion and Reperfusion in Primates Monitored by Microdialysis and Sequential Positron Emission Tomography

Background and Purpose— In a previous investigation concerning the hemodynamic and metabolic changes over time displayed by sequential positron emission tomography (PET) in a middle cerebral artery (MCA) occlusion/reperfusion primate model, a metabolic threshold for irreversible ischemia could be identified (reduction of metabolic rate of oxygen[CMRO2] to ≈60% of the contralateral hemisphere). To evaluate the potential of microdialysis (MD) as an instrument for chemical brain monitoring, the aim of this subsequent study was to relate the chemical changes in MD levels directly to the regional metabolic status (CMRO2 above or below the metabolic threshold) and the occurrence of reperfusion, as assessed by PET. Methods— Continuous MD (2 probes in each brain) and sequential PET measurements were performed during MCA occlusion (2 hours) and 18 hours (mean) of reperfusion in 8 monkeys (Macaca mulatta). Energy-related metabolites (lactate, pyruvate, and hypoxanthine) and glutamate were analyzed. The MD probe regions were divided into 3 categories on the basis of whether CMRO2 was below or above 60% of the contralateral region (metabolic threshold level) during MCA occlusion and whether reperfusion was obtained: severe ischemia with reperfusion (n=4), severe ischemia without reperfusion (n=4), and penumbra with reperfusion (n=5). Results— The lactate/pyruvate ratio, hypoxanthine, and glutamate showed similar patterns. MD probe regions with severe ischemia and reperfusion and probe regions with severe ischemia and no reperfusion displayed high and broad peaks, respectively, during MCA occlusion, and the levels almost never decreased to baseline. Penumbra MD probe regions displayed only slight transient increases during MCA occlusion and returned to baseline. Conclusions— This experimental study of focal ischemia showed that the extracellular changes of energy-related metabolites and glutamate differed depending on the ischemic state of the brain during MCA occlusion and depending on whether reperfusion occurred. If MD proves to be beneficial in clinical practice, it appears important to observe relative changes over time.

A metabolic threshold of irreversible ischemia demonstrated by PET in a middle cerebral artery occlusion–reperfusion primate model*

Objective– to evaluate the predictive value of measurements of regional cerebral blood flow (CBF), oxygen metabolism (CMRO2) and oxygen extraction ratio (OER) for assessment of the fate of ischemic brain tissue. Materials and methods– Sequential PET measurements were performed during middle cerebral artery occlusion (MCAO; 2 h) and 12–24 h (mean 18 h) of reperfusion in a primate model (Macaca mulatta, n=8). A penumbra region was delineated on the MCAO PET image (OER >125% and CMRO2≥45% of the values observed in the contralateral hemisphere, respectively) and an infarction region was delineated on the last PET image (CMRO2<45% of the values observed in the contralateral hemisphere). The penumbra regions delineated during MCAO and the infarction regions delineated at the final PET, were copied on to the images from all other PET sessions for measurements of CBF, CMRO2 and OER. Ratios were calculated by dividing the mean values obtained by the values of the corresponding contralateral region. Results– Histopathology verified the adequacy of the criteria applied in the last PET for delineation of the infarction region. The penumbra region and infarction region were separated in all cases, except in two cases where a minimal overlap was seen. CBF and OER showed considerable variation over time and there was no consistent difference between the penumbra and infarction regions. CMRO2 showed a more stable pattern and the difference between penumbra and infarction regions was maintained from the time of MCAO throughout the entire reperfusion phase. With CMRO2 as predictor, all 50 observations could be correctly predicted as penumbra or infarction when using an optimal threshold ratio value estimated to be in the interval of 61% to 69% of the corresponding contralateral region. CBF and OER proved to have low power as predictors. Conclusions– The results indicate that CMRO2 is the best predictor of reversible or irreversible brain damage and the critical metabolic threshold level appears to be a reduction of oxygen metabolism to between 61% and 69% of the corresponding contralateral region.

Clinical guidelines on central venous catheterisation

Safe and reliable venous access is mandatory in modern health care, but central venous catheters (CVCs) are associated with significant morbidity and mortality, This paper describes current Swedish guidelines for clinical management of CVCs The guidelines supply updated recommendations that may be useful in other countries as well. Literature retrieval in the Cochrane and Pubmed databases, of papers written in English or Swedish and pertaining to CVC management, was done by members of a task force of the Swedish Society of Anaesthesiology and Intensive Care Medicine. Consensus meetings were held throughout the review process to allow all parts of the guidelines to be embraced by all contributors. All of the content was carefully scored according to criteria by the Oxford Centre for Evidence‐Based Medicine. We aimed at producing useful and reliable guidelines on bleeding diathesis, vascular approach, ultrasonic guidance, catheter tip positioning, prevention and management of associated trauma and infection, and specific training and follow‐up. A structured patient history focused on bleeding should be taken prior to insertion of a CVCs. The right internal jugular vein should primarily be chosen for insertion of a wide‐bore CVC. Catheter tip positioning in the right atrium or lower third of the superior caval vein should be verified for long‐term use. Ultrasonic guidance should be used for catheterisation by the internal jugular or femoral veins and may also be used for insertion via the subclavian veins or the veins of the upper limb. The operator inserting a CVC should wear cap, mask, and sterile gown and gloves. For long‐term intravenous access, tunnelled CVC or subcutaneous venous ports are preferred. Intravenous position of the catheter tip should be verified by clinical or radiological methods after insertion and before each use. Simulator‐assisted training of CVC insertion should precede bedside training in patients. Units inserting and managing CVC should have quality assertion programmes for implementation and follow‐up of routines, teaching, training and clinical outcome. Clinical guidelines on a wide range of relevant topics have been introduced, based on extensive literature retrieval, to facilitate effective and safe management of CVCs.

Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury: a controlled experimental study in pigs with saline lavage lung injury

IntroductionProtocols using high levels of positive end-expiratory pressure (PEEP) in combination with low tidal volumes have been shown to reduce mortality in patients with severe acute respiratory distress syndrome (ARDS). However, the optimal method for setting PEEP is yet to be defined. It has been shown that respiratory system reactance (Xrs), measured by the forced oscillation technique (FOT) at 5 Hz, may be used to identify the minimal PEEP level required to maintain lung recruitment. The aim of the present study was to evaluate if using Xrs for setting PEEP would improve lung mechanics and reduce lung injury compared to an oxygenation-based approach.Methods17 pigs, in which acute lung injury (ALI) was induced by saline lavage, were studied. Animals were randomized into two groups: in the first PEEP was titrated according to Xrs (FOT group), in the control group PEEP was set according to the ARDSNet protocol (ARDSNet group). The duration of the trial was 12 hours. In both groups recruitment maneuvers (RM) were performed every 2 hours, increasing PEEP to 20 cmH2O. In the FOT group PEEP was titrated by monitoring Xrs while PEEP was reduced from 20 cmH2O in steps of 2 cmH2O. PEEP was considered optimal at the step before which Xrs started to decrease. Ventilatory parameters, lung mechanics, blood gases and hemodynamic parameters were recorded hourly. Lung injury was evaluated by histopathological analysis.ResultsThe PEEP levels set in the FOT group were significantly higher compared to those set in the ARDSNet group during the whole trial. These higher values of PEEP resulted in improved lung mechanics, reduced driving pressure, improved oxygenation, with a trend for higher PaCO2 and lower systemic and pulmonary pressure. After 12 hours of ventilation, histopathological analysis showed a significantly lower score of lung injury in the FOT group compared to the ARDSNet group.ConclusionsIn a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.

Low-dose oral midazolam reduces fear and distress during needle procedures in children with cancer†

Children with cancer often mention needle procedures as the most frightening, distressing, and sometimes painful aspect of the disease and treatment. The aim was to investigate whether children experience less fear, distress, and/or pain according to parents, nurses, and children ≥7 years of age when they receive oral midazolam versus placebo before a needle is inserted in a subcutaneously implanted intravenous port.

Clinical guidelines on central venous catheterisation. Swedish Society of Anaesthesiology and Intensive Care Medicine.

Safe and reliable venous access is mandatory in modern health care, but central venous catheters (CVCs) are associated with significant morbidity and mortality, This paper describes current Swedish guidelines for clinical management of CVCs The guidelines supply updated recommendations that may be useful in other countries as well. Literature retrieval in the Cochrane and Pubmed databases, of papers written in English or Swedish and pertaining to CVC management, was done by members of a task force of the Swedish Society of Anaesthesiology and Intensive Care Medicine. Consensus meetings were held throughout the review process to allow all parts of the guidelines to be embraced by all contributors. All of the content was carefully scored according to criteria by the Oxford Centre for Evidence‐Based Medicine. We aimed at producing useful and reliable guidelines on bleeding diathesis, vascular approach, ultrasonic guidance, catheter tip positioning, prevention and management of associated trauma and infection, and specific training and follow‐up. A structured patient history focused on bleeding should be taken prior to insertion of a CVCs. The right internal jugular vein should primarily be chosen for insertion of a wide‐bore CVC. Catheter tip positioning in the right atrium or lower third of the superior caval vein should be verified for long‐term use. Ultrasonic guidance should be used for catheterisation by the internal jugular or femoral veins and may also be used for insertion via the subclavian veins or the veins of the upper limb. The operator inserting a CVC should wear cap, mask, and sterile gown and gloves. For long‐term intravenous access, tunnelled CVC or subcutaneous venous ports are preferred. Intravenous position of the catheter tip should be verified by clinical or radiological methods after insertion and before each use. Simulator‐assisted training of CVC insertion should precede bedside training in patients. Units inserting and managing CVC should have quality assertion programmes for implementation and follow‐up of routines, teaching, training and clinical outcome. Clinical guidelines on a wide range of relevant topics have been introduced, based on extensive literature retrieval, to facilitate effective and safe management of CVCs.

Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: an experimental study in a lavage model of lung injury

IntroductionIt is well established that during mechanical ventilation of patients with acute respiratory distress syndrome cyclic recruitment/derecruitment and overdistension are potentially injurious for lung tissues. We evaluated whether the forced oscillation technique (FOT) could be used to guide the ventilator settings in order to minimize cyclic lung recruitment/derecruitment and cyclic mechanical stress in an experimental model of acute lung injury.MethodsWe studied six pigs in which lung injury was induced by bronchoalveolar lavage. The animals were ventilated with a tidal volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the ventilation waveform. Pressure and flow were measured at the tip and at the inlet of the endotracheal tube respectively. Respiratory system reactance (Xrs) was computed from the pressure and flow signals and expressed in terms of oscillatory elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to 24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration and end-inspiration.ResultsDuring deflation the relationship between both end-expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum values at PEEP = 13.4 ± 1.0 cm H2O (mean ± SD) and 13.0 ± 1.0 cm H2O respectively. EX5 was always higher at end-inspiration than at end-expiration, the difference between the average curves being minimal at 12 cm H2O. At this PEEP level, CT did not show any substantial sign of intra-tidal recruitment/derecruitment or expiratory lung collapse.ConclusionsUsing FOT it was possible to measure EX5 both at end-expiration and at end-inspiration. The optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal recruitment/derecruitment as assessed by CT, and the concurrent attenuation of intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical stress.

A comparison of three doses of sufentanil in combination with bupivacaine‐adrenaline in continuous epidural analgesia during labour

Background: Sufentanil is now frequently added to local anaesthetic in labour epidural analgesia. However, this opioid has some side effects such as pruritus, and in higher doses could harm the neonate. The purpose of this study was to compare three doses of sufentanil combined with low‐dose bupivacaine, to determine the lowest appropriate dose.

Comparison of superimposed high-frequency jet ventilation with conventional jet ventilation for laryngeal surgery

BACKGROUND New ventilators have simplified the use of supraglottic superimposed high-frequency jet ventilation (SHFJV(SG)), but it has not been systematically compared with other modes of jet ventilation (JV) in humans. We sought to investigate whether SHFJV(SG) would provide more effective ventilation compared with single-frequency JV techniques. METHODS A total of 16 patients undergoing minor laryngeal surgery under general anaesthesia were included. In each patient, four different JV techniques were applied in random order for 10-min periods: SHFJV(SG), supraglottic normal frequency (NFJV(SG)), supraglottic high frequency (HFJV(SG)), and infraglottic high-frequency jet ventilation (HFJV(IG)). Chest wall volume variations were continuously measured with opto-electronic plethysmography (OEP), intratracheal pressure was recorded and blood gases were measured. RESULTS Chest wall volumes were normalized to NFJV(SG) end-expiratory level. The increase in end-expiratory chest wall volume (EEV(CW)) was 239 (196) ml during SHFJV(SG) (P<0.05 compared with NFJV(SG)). EEV(CW) was 148 (145) and 44 (106) ml during HFJV(SG) and HFJV(IG), respectively (P<0.05 compared with SHFJV(SG)). Tidal volume (V(T)) during SHFJV(SG) was 269 (149) ml. V(T) was 229 (169) ml (P=1.00 compared with SHFJV(SG)), 145 (50) ml (P<0.05), and 110 (33) ml (P<0.01) during NFJV(SG), HFJV(SG), and HFJV(IG), respectively. Intratracheal pressures corresponded well to changes in both EEV(CW) and V(T). All JV modes resulted in adequate oxygenation. However, was lowest during HFJV(SG) [4.3 (1.3) kPa; P<0.01 compared with SHFJV(SG)]. CONCLUSION SHFJV(SG) was associated with increased EEV(CW) and V(T) compared with the three other investigated JV modes. All four modes provided adequate ventilation and oxygenation, and thus can be used for uncomplicated laryngeal surgery in healthy patients with limited airway obstruction.