Tor Inge Tønnessen

Cerebral resuscitation from cardiac arrest: pathophysiologic mechanisms.

Both the period of total circulatory arrest to the brain and postischemic-anoxic encephalopathy (cerebral postresuscitation syndrome or disease), after normothermic cardiac arrests of between 5 and 20 mins (no-flow), contribute to complex physiologic and chemical derangements. The best documented derangements include the delayed protracted inhomogeneous cerebral hypoperfusion (despite controlled normotension), excitotoxicity as an explanation for selectively vulnerable brain regions and neurons, and free radical-triggered chemical cascades to lipid peroxidation of membranes. Protracted hypoxemia without cardiac arrest (e.g., very high altitude) can cause angiogenesis; the trigger of it, which lyses basement membranes, might be a factor in post-cardiac arrest encephalopathy. Questions to be explored include: What are the changes and effects on outcome of neurotransmitters (other than glutamate), of catecholamines, of vascular changes (microinfarcts seen after asphyxia), osmotic gradients, free-radical reactions, DNA cleavage, and transient extracerebral organ malfunction? For future mechanism-oriented studies of the brain after cardiac arrest and innovative cardiopulmonary-cerebral resuscitation, increasingly reproducible outcome models of temporary global brain ischemia in rats and dogs are now available. Disagreements exist between experienced investigative groups on the most informative method for quantitative evaluation of morphologic brain damage. There is agreement on the desirability of using not only functional deficit and chemical changes, but also morphologic damage as end points.

Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure.

Background Studies in different animal models and plasma analyses in humans suggest that members of the interleukin‐6 (IL‐6) cytokine family may be involved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL‐6‐related cytokines in chronic CHF in humans by analysing gene and protein expression in myocardium derived from patients with end‐stage heart failure and donor hearts.

Agreement between PiCCO pulse-contour analysis, pulmonal artery thermodilution and transthoracic thermodilution during off-pump coronary artery by-pass surgery

Background:  Haemodynamic instability during off‐pump coronary artery bypass surgery (OPCAB) may appear rapidly, and continuous monitoring of the cardiac index (CI) during the procedure is advisable. With the PiCCO monitor, CI can be measured continuously and almost real time with pulse‐contour analysis and intermittently with transthoracic thermodilution. The agreement between pulmonal artery thermodilution CI (Tpa), transthoracic thermodilution CI (Tpc) and pulse‐contour CI (PCCI) during OPCAB surgery has not been evaluated sufficiently.

A randomized double-blind controlled trial of intra-annular radiofrequency thermal disc therapy--a 12-month follow-up.

ABSTRACT The discTRODE™ probe applies radiofrequency (RF) current, heating the annulus to treat chronic discogenic low back pain. Randomized controlled studies have not been published. We assessed the long‐term effect and safety aspects of percutaneous intradiscal radiofrequency thermocoagulation (PIRFT) with the discTRODE™ probe in a prospective parallel, randomized and gender stratified, double‐blind placebo‐controlled study. Twenty selected patients with chronic low back pain and a positive one‐level pressure‐controlled provocation discography were randomized to either intra‐annular PIRFT or intra‐annular sham treatment. A blinded interim analysis was performed when 20 patients had been followed for six months. The 6‐month analysis did not reveal any trend towards overall effect or difference between active and sham treatment for the primary endpoint: change in pain intensity (0–10). The inclusion of patients was therefore discontinued. After 12 months the overall reduction from baseline pain had reached statistical significance, but there was no significant difference between the groups. The functional outcome measures (Oswestry Disability Index, and SF 36 subscales and the relative change in pain) appeared more promising, but did not reach statistical significance when compared with sham treatment. Two actively treated and two sham‐treated patients reported increased pain levels, and in both groups a higher number was unemployed after 12 months. The study did not find evidence for a benefit of PIRFT, although it cannot rule out a moderate effect. Considering the high number, reporting increased pain in our study, we would not recommend intra‐annular thermal therapy with the discTRODE™ probe.

CD14 inhibition efficiently attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis in pigs

Sepsis is a severe infection‐induced systemic inflammatory syndrome. Inhibition of downstream inflammatory mediators of sepsis, e.g., TNF‐α, has failed in clinical trials. The aim of this study was to investigate the effects of inhibiting CD14, a key upstream innate immunity molecule, on the early inflammatory and hemostatic responses in a pig model of gram‐negative sepsis. The study comprised two arms, whole live Escherichia coli bacteria and E. coli lipopolysaccharide (LPS) (n=25 and n=9 animals, respectively). The animals were allocated into treatment (antiCD14) and control (IgG isotype or saline) groups. Inflammatory, hemostatic, physiological, and microbiological parameters were measured. The proinflammatory cytokines TNF‐α, IL‐1β, IL‐6, and IL‐8, but not the anti‐inflammatory cytokine IL‐10, were efficiently inhibited by anti‐CD14. Furthermore, anti‐CD14 preserved the leukocyte count and significantly reduced granulocyte enzyme matrix metalloproteinase‐9 release and expression of the granulocyte membrane activation molecule wCD11R3 (pig CD11b). The hemostatic markers thrombin‐antithrombin III complexes and plasminogen activator inhibitor‐1 were significantly attenuated. Anti‐CD14 did not affect LPS or E. coli DNA levels. This study documents that CD14 inhibition efficiently attenuates the proinflammatory cytokine response and granulocyte activation and reverses the procoagulant state but does not interfere with LPS levels or bacterial counts in E. coli‐induced sepsis.— Thorgersen, E. B., Hellerud, B. C., Nielsen, E. W., Barratt‐Due, A., Fure, H., Lindstad, J. K., Pharo, A., Fosse, E., Tønnessen, T. I., Johansen, H. T., Castellheim, A., Mollnes, T. E. CD14 inhibition efficiently attenuates early inflammatory and hemostatic responses in Escherichia coli sepsis in pigs. FASEB J. 24, 712–722 (2010). www.fasebj.org

Quality of life after randomization to laparoscopic versus open living donor nephrectomy: long-term follow-up.

Background. The aim of this randomized study was to compare patient-reported outcome after laparoscopic versus open donor nephrectomy during 1 year follow-up. The evidence base has so far not allowed for a decision as to which method is superior as seen from a long-term quality of life-perspective. Methods. The donors were randomized to laparoscopic (n=63) or open (n=59) nephrectomy, with follow-up at 1, 6, and 12 months. Primary outcomes were health status (SF-36) and overall quality of life (QOLS-N). Secondary outcomes were donor perception of the surgical scar, the donation’s impact on personal finances, and whether the donor would make the same decision to donate again. Results. There was a significant difference in favor of laparoscopic surgery regarding the SF-36 subscale bodily pain at 1 month postoperatively (P<0.05). Analysis based on intention to treat revealed no long-term differences between groups in SF-36 scores. When subtracting the reoperated/converted donors of the laparoscopic group, significant differences in favor of laparoscopy were revealed in the subscales bodily pain at 6 months (P<0.05) and social functioning at 12 months (P<0.05). No significant differences were found in QOLS-N scores between groups. Conclusions. Laparoscopic donor nephrectomy is an attractive alternative to open donor nephrectomy because of less postoperative pain. However, long-term comparison only revealed significant differences in favor of laparoscopy when adjusting for reoperations/conversions. Both groups reached baseline scores in most SF-36 subscales at 12 months and this may explain why possible minor benefits are hard to prove.

Laparoscopic and open surgery for pheochromocytoma

BackroundLaparoscopic adrenalectomy is a promising alternative to open surgery although concerns exist in regard to laparoscopic treatment of pheocromocytoma. This report compares the outcome of laparoscopic and conventional (open) resection for pheocromocytoma particular in regard to intraoperative hemodynamic stability and postoperative patient comfort.MethodsSeven patients laparoscopically treated (1997–2000) and nine patients treated by open resection (1990–1996) at the National Hospital (Rikshospitalet), Oslo. Peroperative hemodynamic stability including need of vasoactive drugs was studied. Postoperative analgesic medication, complications and hospital stay were recorded.ResultsNo laparoscopic resections were converted to open procedure. Patients laparoscopically treated had fewer hypertensive episodes (median 1 vs. 2) and less need of vasoactive drugs peroperatively than patients conventionally operated. There was no difference in operative time between the two groups (median 110 min vs. 125 min for adrenal pheochromocytoma and 235 vs. 210 min for paraganglioma). Postoperative need of analgesic medication (1 vs. 9 patients) and hospital stay (median 3 vs. 6 days) were significantly reduced in patients laparoscopically operated compared to patients treated by the open technique.ConclusionSurgery for pheochromocytoma can be performed laparoscopically with a safety comparable to open resection. However, improved hemodynamic stability peroperatively and less need of postoperative analgesics favour the laparoscopic approach. In experienced hands the laparoscopic technique is concluded to be the method of choice also for pheocromocytoma.

Microdialysis Monitoring of Liver Grafts by Metabolic Parameters, Cytokine Production, and Complement Activation

Introduction. The outcome of liver transplantation is steadily improving. Still there is need for earlier detection of complications like hepatic artery thrombosis and rejection. The aim of this study was to explore whether microdialysis with a 100-kDa cutoff filter could be used to monitor local inflammation after liver transplantation. Methods. Twenty patients undergoing liver transplantations were observed for 1 week posttransplant. Microdialysis catheters were introduced in each liver lobe subcutaneously and metabolic parameters (glucose, pyruvate, glycerol, and lactate), cytokines (interleukin [IL]-6, IL-8, monocyte chemottractic protein-1, and inducible protein [IP]-10), and complement activation (C5a) were measured. Results. Fourteen patients experienced an uneventful course, judged clinically by ultrasound Doppler and by metabolic markers including lactate and the ischemia indicator lactate-to-pyruvate ratio. All patients with uneventful course had a consistent rise in IP-10 from 200 to 3000 pg/mL after transplantation, whereas the other cytokines stayed low. Two patients with rejection showed a selective increase in IL-8 and C5a, starting 2 to 4 days before alanine transferase increased, reaching 10- to 50-fold increase compared with baseline levels, and decreased rapidly after start of antirejection therapy. C5a concentration was substantially increased in these two patients at the time of transplantation. A third patient developed a hepatic artery thrombosis and rejection and showed a rapid rise in intrahepatic lactate and a complex inflammatory pattern. Conclusion. Microdialysis using a 100-kDa filter is a promising way of monitoring the inflammatory reaction after liver transplantation. Increase in IP-10 reflects a normal pathophysiologic response posttransplant, whereas IL-8 and C5a were increased only in patients with rejection.

Microdialysis for Monitoring Inflammation: Efficient Recovery of Cytokines and Anaphylotoxins Provided Optimal Catheter Pore Size and Fluid Velocity Conditions

Microdialysis emerges as a useful tool to evaluate tissue inflammation in a number of clinical conditions, like sepsis and transplant rejection, but systematic methodological studies are missing. This study was undertaken to determine the recovery of relevant inflammatory mediators using the microdialysis system, comparing microdialysis membranes with two different molecular weight cut‐offs at different flow rates. Twenty and 100 kDa pore sizes CMA microdialysis catheters were investigated using velocities of 0.3, 1.0 and 5.0 μl/min. Reference preparations for cytokines [tumour necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6 and IL‐10; m.w. 17–28 kDa] and chemokines (IL‐8, MCP‐1, IP‐10 and MIG; m.w. 7–11 kDa) were prepared from plasma after incubating human whole blood with lipopolysaccharide. Reference preparation for complement anaphylatoxins (C3a, C4a, C5a; m.w. 9–11 kDa) was prepared by incubating human plasma with heat‐aggregated immunoglobulin G. The reference preparations were quantified for the respective inflammatory molecules and used as medium for the microdialysis procedure. Through the 20 kDa filter only the four chemokines passed, but with low recovery (3–7%) and limited to the 1.0 μl/min velocity. The recovery with the 100 kDa filter was as follows: IL‐1β = 75%, MCP‐1 = 55%, MIG = 50%, IL‐8 = 38%, C4a = 28%, IP‐10 = 22%, C5a = 20%, C3a = 16%, IL‐6 = 11, IL‐10 = 8% and TNF‐α = 4%. The highest recovery for all chemokines and anaphylatoxins were consistently at velocity 1.0 μl/min, whereas IL‐1β and IL‐10 recovered most efficiently at 0.3 μl/min. Thus, microdialysis using catheters with a cut‐off of 100 kDa is a reliable method to detect inflammation as judged by a defined panel of inflammatory markers. These findings may have important implications for future clinical studies.

MRI-guided celiac plexus block

Celiac plexus block is used as a palliative procedure in cases of severe upper abdominal pain caused by pancreatitis or tumors of the pancreas. It can be guided by bony landmarks, fluoroscopy, ultrasound (US), or computed tomography (CT). To avoid severe complications, methods visualizing soft tissue, like CT and magnetic resonance (MR) imaging, are preferable. We describe celiac plexus blocks carried out in an open MR scanner, offering needle guidance with an optical tracking system and near real‐time image acquisition. Eight patients with severe chronic abdominal pain were included. In these, 14 celiac blocks were carried out. Good or total pain relief was achieved in 8 of the 14 blocks (57%), a moderate effect in 5 blocks (36%), and no effect in 1 block (7%). The placement of the needle was easily guided with MR in all cases. The MR technique ensures good visualization of soft tissue, direct monitoring of needle movement and avoids exposure to ionizing radiation. Celiac plexus block can safely be carried out in an open MR scanner. J. Magn. Reson. Imaging 2000;12:562–564.