Principal investigator: Sten Rubertsson
Hypothermia treatment to 32-34 °C during 24 hours after cardiac arrest has been shown to improve survival and neurologic outcome. Fifty percent of the admitted patients treated by hypothermia are now surviving. Hypothermia after global ischemia in cardiac arrest patients can be induced with both invasive and noninvasive methods with varying efficiency. Since there is a risk for side effects and complications with systemic hypothermia, a more selective cooling of the brain might be an alternative in treatment of global or focal ischemic brain injury after cardiac arrest trauma or stroke. We have together with researchers from Lund University developed a new intranasal cooling method using balloon catheters introduced into the nasopharynx with cold saline solution circulated in a closed circuit with a pump and heater exchanger. Different methods have been used for early prognostification in the effort to improve treatment. Markers of brain injury that have been investigated in cardiac arrest patients treated with hypothermia are S-100β (astroglial protein) och NSE (neuronspecific enolas). Continous EEG registration of patients during and after hypothermia treatment is of prognostic value in one study. EEG will also detect epileptic activity requiring treatment. For the cardiac arrest patient not only survival is of major importance but also how quality life will be affected.
Questions: Will this new intranasal cooling method be clinically feasible in patients together with infusion of cold saline i v to effectively cool the brain and body after cardiac arrest and maybe also in the future patients with stroke or traumatic brain injury? The aim is also to follow-up patients during the first 6 months after cardiac arrest treated by hypothermia and study quality of life, physical and psychological function, neurologic function and mortality in relation to initial levels of markers of brain injury. Finally, the aim is to describe the influence on relative’s daily life.
Methods and results: Experimental studies have shown that the brain will be selectively cooled during normal circulation. In both experimental and clinical studies we have shown that brain temperature will decrease measured by MR spectroscopy. This technique will now undergo testing for feasibility in pilot studies of patients after cardiac arrest. Markers of brain injury are sampled directly after the patient is admitted to hospital and followed up to 108 hrs after cardiac arrest. MRI of the brain is done five days after the cardiac arrest and EEG will be monitored up to 48 hrs after cardiac arrest. Follow-up of the patients will be performed at discharge from the hospital one and sex months after the cardiac arrest. Next of kin will be interviewed first when the patient is discharged from hospital and at sex months after the injury.
Members of the group in 2013
Sten Rubertsson, Professor
Erik Mörtberg, MD, PhD
Lucian Covaciu, MD, PhD student
Erik Lindgren, MD, PhD student
Ing-Marie Larsson, RN, PhD student
Eva C Wallin, RN, PhD student
Marja Leena Kristofferzon, RN, PhD Senior Registrar Gävle University
Marie Sellert-Rydberg, RN Falu Hospital
In collaboration with
Håkan Ahlström, Professor Dept. of Radiology
Jan Weis, Engineer, Associate Professor Dept. of Radiology
Background: Every year 300 000 to 400 000 people suffer from sudden cardiac arrest outside of the hospital in Europe. Only 5-9 % of these patients survives and is discharged from hospital. Lately, there is a strong emphasis on chest compressions being delivered without interruptions. Manual chest compressions during CPR result in only 20-30% of normal blood flow and are difficult to perform continuously. Mechanical chest compressions with the LUCAS device have shown increased cerebral blood flow, coronary perfusion pressure and survival in experimental studies.
Questions: Can mechanical chest compressions with the LUCAS device combined with defibrillation during ongoing chest compressions improve survival? Will treatment with the LUCAS device result in more injuries in non surviving patients.
Methods and results: Defibrillation during ongoing mechanical compressions showed promising results with a trend in increased short time survival in out of hospital cardiac arrest in a recently completed pilot study of 149 patients. Autopsy was performed in 85 non surviving patients after being treated with either mechanical chest compressions with the LUCAS device or with manual chest compressions according to guidelines. There were no injuries in one third of the patients in both groups. The most frequent injuries found were rib fractures and sternal fractures but there was no difference between the groups. No fatal injuries were found in any of the groups. The results from this pilot studies are the foundation for a multicenter study in Europe-the LINC study of 2 500 patients with out-of hospital cardiac arrest. The study started in January 2008 and will continue to 2012. Patients with cardiac arrest will be randomized to either treatment with a concept using mechanical chest compressions with the LUCAS and defibrillation during ongoing compressions or treatment according to international guidelines including manual chest compressions. In January 2011, an interimanalysis will be performed to allow inclusion of the entire study population. Within this study, non surviving patients in Uppsala, Gävle and Västerås will undergo autopsy.
Members of the group during 2013
Sten Rubertson, Professor
Jakob Johansson, MD, PhD
David Smekal, MD, PhD student
Erik Lindgren, MD, PhD student
In collaboration with
Steering com for the LINC trial
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Principal investigator: Lars Wiklund
Background: Trauma is the main cause of death in citizens of the whole west hemisphere between the ages 1 and 38 years. It is estimated that by year 2020 deaths from injury are predicted to increase up to 8.4 million world-wide and uncontrolled haemorrhage will be responsible for 30% of these deaths. Despite improvements in resuscitation techniques and surgical management of trauma victims, survival rates remain extremely low in trauma patients who exsanguinate to cardiac arrest and have not improved significantly during the last decades. Thus, resuscitation from hemorrhagic shock and subsequent cardiac arrest is a major clinical challenge in the care of patients after motor vehicle accidents, gunshot or stab wounds, and combat. Nevertheless, even after successful restoration of spontaneous circulation (ROSC) following cardiac arrest, the morbidity and mortality depend mainly on the recovery of neurological function. However, the immediate challenge in emergency and operating rooms also when handling these in many instances young patients is to achieve restoration of spontaneous circulation that is the ultimate aim and demand in order to achieve preservation of neurological function.
This is because the general experience in such situations is that even after very short circulatory arrests it is often almost impossible to achieve ROSC, in contrast to normovolaemic cardiac arrests of considerably longer duration. This has been confirmed also experimentally, and in addition, we have also observed that intrathoracic cardiac massage is a prerequisite for success. Different blood volume substitutes have been tried and hypertonic saline with dextran has so far been superior to autologous blood and Ringer’s acetate. Block of nitric oxide action has not improved the results, in contrast to normovolaemic cardiac arrests of longer duration. Hypovolaemic cardiac arrests of somewhat longer duration can be successfully treated when and if an antiarrhythmic agent (amiodar-one) is administered during open thoracic CPR. Lately gender differences in circulatory and cerebral adaptation to ischaemia have been investigated in immature piglets where there is no differences in sexual hormone concentration in plasma. We have found that female piglets have a better capacity to adapt both circulatory and cerebral parameters to serious ischaemia. Methylene blue, probably by its inhibitory action on the nitric oxide-guanylyl cyclase pathway, improves circulatory and cerebral adaptation to ischaemia only in male piglets. However, not quite up to the still better level in female piglets. Our findings do indicate that female animals already before having sexual hormones have a better innate protection against ischaemia than their male counterparts.
Members of the group in 2013
Lars Wiklund, Professor
Ingemar Thiblin, Professor in Forensic Medicine
Sten Rubertsson, Professor
Hari Shanker Sharma, PhD, Associate Professor
Ala Nozari, MD, PhD Harvard Medical School
Egidijus Semenas, MD, PhD student
At the section of cardiothoracic anesthesia and intensive care, clinical and experimental research is performed in collaboration mainly with the section of cardiothoracic surgery and the department of anesthesiology and intensive care. Several cardiothoracic anesthesiologists and one perfusionist are involved in projects of high clinical relevance, for instance cerebral perfusion during cardiopulmonary bypass, cerebral perfusion during aortic arch surgery, coagulation/hemostasis, the physiology of one-lung ventilation and the effects of hyperglycemia.
Contact: Dr Fredrik Lennmyr (e-mail)
Read more about different research projects from the Cardiothoracic and intensive care section.
Background: During the last decades outcome after myocardial infarction has improved tremendously. The same cannot be stated about cardiac arrest. In spite of intense research and training of medical staff only about five percentage of the patients brought in to the emergency rooms after witnessed cardiac arrest survive, and out of those surviving many have neurological deficits. However, not many of the patients survive in neurological vegetative states, the main problem being that those being hurt by a ischaemic cerebral injury die within weeks. When the National Institute of Health some years ago came out with a statement on this problem, it was obvious that no better outcome than in the 1960’s could be expected now unless substantial progress in the field of ischaemic neurological protection could be achieved. After this statement was made public, however, a significant improvement has been published when two different groups independently have found that therapeutic hypothermia in the range 34-32 º C during 24 hours after resuscitation from a cardiac arrest improved survival and neurological outcome. This has changed the chances to find also pharmacological agents that could have the same or even better effects in this situation. In addition it is possible to make valid comparisons between effects of hypothermia and suggested pharmacological agents for screening purposes. A few hundred of such pharmacological compounds have already been tested in different experimental models, and at least one agent has been brought a stage 2 controlled clinical trial, where it unfortunately failed. This knowledge makes it possible both to make comparisons with a successful method as well as with a failing one. All these facts, also including new evidence of why artificial circulation during cardiopulmonary resuscitation (CPR) more or less always is insufficient and that there is no single receptor or molecular mechanism that, when used, elicits efficient neuroprotective mechanisms, has resulted in a knowledge background that seems to indicate that it seems highly probable that efficient neuroprotection after ischaemia and reperfusion is indeed possible.
Action taken: Since a decade we have had an experimental well-functioning model of cardiac arrest in piglets. Gradually the arrest period has been possible to increase. Presently we use a cardiac arrest of 21-23 min including eight minuts CPR, and a follow-up period of at least three hours. After this the animal is sacrificed and the heart and the brain are harvested within a minute. The molecular biology of especially the brain is studied by microarrays, quantitative PCR and protein staining methods.
Considerable evidence has so far been collected implying that different neuroprotective mechanisms and pharmacological agents exhibit both similarities and differences as regards effects in gene activation and proteomics. It seems that block of nitric oxide elicited mechanisms seem essential for successful neuroprotection after long cardiac arrests. During 2010 we have published two major articles on cerebral structural and gene activation changes after cardiac arrest and CPR. In addition we have found that tight management of glucose blood concentrations does not have a major influence on cerebral injury after cardiac arrest and CPR. In contrast, in the same situation the anaesthetic agent propofol seems to decrease cerebral oxidative injury. We have demonstrated experimentally that induced mild hypothermia activates the endothelin system explaining the marked circulatory stability often experienced during mild induced hypothermia after cardiac arrest and CPR. Lately we have established that administration of methylene blue during cardiopulmonary resuscitation markedly potentiates the neuroprotective effects of induced mild hypothermia after cardiac arrest.
Members of the group during 2013
Lars Wiklund, Professor
Cecile Martijn, PhD postdoc
Hari Shanker Sharma, PhD, Associate Professor
Samar Basu, PhD
Fredrik Lennmyr, MD, PhD
Adriana Miclescu, MD, PhD
Egidijus Semenas, MD, PhD student
Maria Molnar, MD, PhD student
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Principal investigator: Rolf Gedeborg
Injuries are the most important cause of death in the young and middle aged and a common reason for ICU admission. Injury epidemiology is an integrated part of the Epidemiological & Statistical Group (EpiStat) at Uppsala Clinical Research Center. With the aid of unique person identification numbers to link health care registers, we have excellent opportunities for population-based research. Each year approximately 100 000 people in Sweden are hospitalized because of injuries and 5 000 people die from their injuries.
Injury epidemiology is a collaborative effort involving several sections of the department, among them the sections for Anesthesiology and Intensive Care, Orthopedics, Plastic surgery, Vascular surgery and Forensic Medicine. International collaboration in several projects has also been established with the International Collaborative Effort on Injury Statistics (ICE).
During the year, the focus has been to develop methods for injury epidemiology and its practical application. The ability to identify and study prehospital injury deaths and consequences of prehospital management remains a focus. A study on the association between population density and mortality after traffic crashes has been published along with a study on the quality of injury coding in hospital discharge data. We continue to develop the ICD-10 injury severity score in collaboration with ICE researchers in seven other countries. A joint publication on the importance of prehospital injury deaths is underway and the collaborative effort continues with the aim of defining valid indicators of injury incidence and improving injury severity models. A particular focus of our efforts is also on the ability to develop reliable estimates of comorbidity in hip fracture patients. We also continue to work with Bayesian models to improve injury severity estimation. In collaboration with Forensic Medicine we have develop prediction models for the outcome after violent crime.
We have also during the year participated in the development of a course in epidemiological methods given at the doctoral level. As a part of the Uppsala Clinical Research Center we also offer consultations in epidemiological methods and study design.
Members of the group during 2013
Rolf Gedeborg, Associate Professor
Jakob Johansson, PhD
Hans Blomberg, PhD student
Karin Andersson, PhD student
In collaboration with
Karl Michaëlsson, Professor
Ingemar Thiblin, Professor
Liisa Byberg, PhD
Håkan Melhus, Professor
Margaret Warner, Injury Epidemiologist NCHS CDC USA
James Harrison, Professor Research Centre for Injury Studies Flinders University South Australia
Principal Investigator: Anders Larsson
The project is primarily aimed at improving ventilator treatment in the critically ill patient with acute respiratory failure (ARF). The secondary aim is to increase the understanding of respiratory physiology at spontaneous and mechanical ventilation during anesthesia and intensive care. The project is mainly performed at the Hedenstierna laboratory (a part of the Dept of Surgical Sciences) and in the Central Intensive Care Unit, Uppsala University hospital in collaboration with professor Göran Hedenstierna as well as coworkers from Karolinska Institute, University of Bari, Politecnico di Milano University, University of Magdeburg, University of Freiburg, University of Istanbul and University of Sao Paolo.
About 3 000 patients are treated with mechanical ventilation in the Swedish intensive care units due to ARF, a condition with mortality of about 30-40%. Although mechanical ventilation saves lives, it has inherent side effects by inducing mechanical injury on the lungs, leading to local and systemic inflammation. In fact, the patients do not die of hypoxemia but of multiple organ failure caused by the inflammation. It has been shown that by decreasing the mechanical stress on the lungs by reducing the tidal volumes, mortality is reduced by ten absolute percent. In a present project we are studying in an experimental ARF model with positron emission tomography (PET) and immunohistology the inflammatory effects of two different ventilator modes; a conventional and an experimental, new, protective mode (low tidal volumes and lung recruitment i.e., opening of closed lung regions by applying high airway pressure). Preliminary results indicate that the experimental mode induces less severe inflammation. Another new, interesting finding is that the inflammation is mainly located in the “healthy” open parts of the lungs and not, as previously thought in the collapsed lung regions.
Positive end-expiratory pressure (PEEP) is used to keep the lung open during the expiratory phase of the ventilator breath in ARF. Too low PEEP will induce lung collapse with hypoxemia, whereas too high PEEP might cause overdistension as well as circulatory compromise. Forced oscillation technique (FOT), a new technique that measures the mechanical properties of the respiratory system, has recently been shown by coworkers in the group to be able to indicate the amount of collapsed lung tissue. Therefore, we have studied whether FOT could be used to set “optimal” PEEP in an experimental ARF model. Preliminary results suggest that inflammation in the lungs is reduced compared with a conventional PEEP setting.
In the wet, heavy ARF lung the collapsed part in is mainly located in the “lower” regions due to gravitation. In order to open (recruit) these collapsed lung regions (see above) and to keep it open a very high pressure is therefore sometimes needed. However, this high pressure may cause injuries in the upper “healthy” lung (see above) by overdistension and therefore the beneficial positive effect of open the lower parts of the lungs might be neutralized by the negative effect by overdistension in the upper part of the lungs. One way to overcome this problem is to put the subject in the lateral position and ventilate the lower and upper lung with different pressures (lower pressure to the upper and higher pressure the lower lung) via a double lumen tube (that makes it possible to direct ventilation separately to the right and the left lung). This new method is now studied experimentally using computed tomography, measurements of lung volume and mechanics in each lung, blood gases and electric impedance tomography (EIT).
Modes in which spontaneous breathing efforts are allowed have been shown, except improving the patient’s comfort, to improve oxygenation in ARF. The underlying mechanism has previously been thought to be caused by recruitment of collapsed lung tissue located close to the diaphragm, but studies by us in an experimental model have shown that the explanation is that perfusion is redistributed to open and ventilated lungs regions during spontaneous breathing. We are exploring the effect of spontaneous breathing further on lung perfusion in present studies. We hypothesize that the redistribution of perfusion is caused by a higher transmission of the negative alveolar pressure to the pulmonary vasculature in non-HPV regions of the lungs.
As discussed above, low tidal ventilation improves survival in ARF. The ultimate ventilation would be a mode with zero tidal ventilation, i.e. apneic ventilation. We have recently shown that apneic ventilation in combination with ECCO2R gave excellent oxygenation and blood CO2 levels in an experimental ARF model. However, to prevent alveolar nitrogen concentration/accumulation in the lungs with this technique 100% O2 (which is toxic) is thought be needed. We have now successfully explored a modified apneic ventilation technique in an experimental lung model, where the alveolar O2 concentration could be kept at non-toxic levels, and we will further develop and examine this technique . In addition, we are exploring whether high CO2 levels can be tolerated by the use of a proton-catcher, THAM, and whether a combination of low tidal volume ventilation combined with THAM would be as effective and safe as low tidal volume ventilation combined with ECCO2R.
ECMO treatment is an essential modality when advanced ventilator treatment fails to provide adequate oxygenation or CO2 removal in patients with ARF. This treatment is resource intensive and is centralised in Sweden to the ECMO center at the Karolinska hospital, which treat about 50 adult patients with ECMO for ARF with a survival rate comparable with (about 60%) the normal ARF population despite these patients are more severely ill. However, the evolution of lung function during the ECMO treatment has not been studied. This is very important issue since the optimal management of the lungs during ECMO is not known, and it possible that a change of the handling of the lungs would further improve the results. We are planning a prospective study with lung mechanical investigations, imaging (EIT, Computed Tomography and PET) as well as inflammatory markers (TNF, IL1, IL6, IL8, IL10) from the lungs (obtained by bronchoalveolar lavage ) on the patients treated at the Karolinska ECMO center.
Intubation of the trachea in critically ill patients is associated with severe complications in about 20% of the case, mainly caused by hypoxemia. We have shown that a simple method, nasopharyngeal oxygen administration, effectively prolongs the time of safe oxygenation during this procedure. We are also investigating the risk of disconnecting the ventilatory tubing during ventilator treatment and the ventilatory risks of common nursing procedures in the intensive care unit.
In obese patients undergoing anaesthesia severe hypoxemia may develop due to rapid occurring lung collapse. We have showed that this could be ameliorated by applying a lung recruitment maneuver and continuing with PEEP (see above). Another patient group that is subjected to severe hypoxemia and compromised lung function is patients undergoing one-lung ventilation combined with pressurized capnothorax for surgical treatment of atrial fibrillation. In an experimental study we have suggested a method to optimize the lung function.
Optoelectronic plethysmography, in which the dimensions of thorax and abdomen are determined in real time by registration of the movement of reflective markers on the chest wall by several video cameras, is a non-invasive method to measure with high resolution the changes in thorax and abdomen induced by breathing and the anesthesia technique. The method has been used to study the ventilatory mechanical effects of propofol anesthesia and of different modes of jet ventilation. Interesting findings about the ventilator pattern at emergence from anesthesia make us to continue to study effect of other anesthetics focused on this part of the anesthetic procedure.
It is not known how volatile anesthetic agents are taken up in the lungs in patients with obstructive lung disease (asthma and chronic obstructive lung disease) or with ARF (intrapulmonary shunt). We have found using a mass-spectrometry technique, that there is a delay in the uptake in an obstructive lung, porcine, model, indicating that this might be taken in consideration both during induction and emergence from anesthesia using volatile agents.
Members of the group during 2013
Anders Larsson, Professor
Fernando Suarez Sipmann, MD, PhD
Peter Frykholm, MD, PhD
João Bapista Borges, MD, PhD
Fredrik Lennmyr, MD, PhD
Laszlo Vimlati, MD, PhD
Filip Freden, MD, PhD
Rafael Kawati, MD, PhD
Robert Sűtterlin, MD, PhD student
Peter Kostic, MD, PhD student
Henrik Reinius, MD, PhD student
Staffan Höstman, MD, PhD student
Joakim Engström, MD, PhD student
Moritz Kretzscmar, MD, PhD student
Arnaldo Santos, MD, PhD student
Göran Hedenstierna, Professor Inst Med Sciences Uppsala University
Kristina Hambreus Jonzon, MD, PhD Karolinska Hospital
Bernard Holzgraphe, MD, PhD student, Karolinska Hospital
Michael Lichtwarck-Aschoff, Ass. Professor University of Freiburg Germany
In collaboration with
A. Pedotti, PhD Politechnico di Milano Milan Italy
A. Aliverti, PhD Politechnico di Milano Milan Italy
M. Quaranta, PhD Politechnico di Milano Milan Italy
E. Zennin, Politechnico di Milano Milan Italy
R. Dellaca, Politechnico di Milano Milan Italy
M. Amato, MD, PhD, Univerity of Sao Paolo Brazil
T. Hachenberg, MD, PhD, Professor, Otto–von-Guernicke University Madgeburg, Germany
A. Kozian, MD, PhD, Otto-von-Guernicke University Madgeburg, Germany
M. Senturk, Professor, University of Istanbul Turkey
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Principal Investigator: Torsten Gordh
A cooperation with Uppsala Berzelii center. The aim is to collect blood samples and tissue from very well charachterized groups of pain patients, and to analyze relevant biomarkers. We have in this project access to extremely sensitive analytic methods, in cooperation with prof Ulf Landegren (the PLA method) and prof Jonas Bergquist (mass spec). It is run as a PhD student project by Anne-Li Lind.
In this project we investigate some PET ligands concerning their capacity to mark for painful processes in the body. We have found markers that distinctly accumulates in painful areas in patients suffering from chronic WAD, and following wrist distortions. Experimental studies in “small animal PETscan” is ongoing, in order to pin point to what cellular structure the relevant markeer is binding to.
This is a PhD project for dr Mikko Aarnio.
In this project, mechanisms of neuropathic pain are explored by a combination of clinical routine methods and a range of newly developed techniques to objectively test neuronal function. Three basic approaches are combined:
- Patient evaluation including quantitative sensory testing and newly developed objective tests for C-fiber function
- Microneurography allowing for single fiber recordings to assess specific functional changes in sensory and axonal membrane properties.
Skin biopsies to assess structural changes of axons and endings including modulated channel expression (results being provided by collaboration with Frank Rice, Albany, USA).
In this project, a genetic analysis of patients who have developed chronic pain after inguinal hernia surgery are compared with patients that had undergone the same type of surgery and not developed pain. About 2500 patients have been screened, resulting in 100 with persistant pain + 100 without pain who all have been investigated clinically. The results show that persistant postoperative pain in mainly of neuropathic character. The project is done in collaboration with professor Fred Nyberg.
We are undertaking a study on long term effects, side effects and effects on quality of life, opioid receptor polymorphism as related to effect, and nerve cell culture receptor studies efter chronic opioid exposure. In addition a clinic pharmacokinetic analysis of methadone in pain patients is ongoing.
This project lead to a successful PhD dissertation for dr Annica Rhodin in September 2010.
A collaboration with Doc Anders Fredriksson, in a PhD project for Emma Pontén.
We plan for Med. Lic dissertation during the spring 2011, aiming for PhD in two years time.
Members of the group during 2013
Torsten Gordh, Professor Pain Research Anaesthesiology
Maija-Lisa Kalliomäki, MD, PhD, Post doc
Annica Rhodin, MD, PhD student
Johanna von Kieseritzky, MD Hand Surgery, PhD student
Emma Pontén, MD, PhD student
Mikko Aarnio, MD
Anne-Li Lind, PhD student
Jurgen Fischer, MD
In collaboration with
Roland Schmidt, MD, PhD Clinical Neurophysiology
Martin Schmelz, Professor University of Heidelberg
Rolf Karlsten, MD, PhD ASTRAZENECA
Björn Hägglöf, Resercher ASTRAZENECA
Anders Fredriksson, PhD Psychiatry
Fred Nyberg, Professor Uppsala University
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Principal investigator: Sten Rubertsson
Background: Laparoscopic surgery has in general been known because of several advantages for the patient compared to open surgery such as less pain, shorter hospital stay and shorter periods of sick leave. The technique has developed from initial use for an increasing number of surgical procedures in the abdomen and pelvic region. To improve the view and the availability for the surgeon CO2 is inflated into the abdomen in the beginning of the procedure. A rare but feared complication due to this inflated gas is the risk for venous CO2–embolisation where even fatal cases have been reported in liver surgery. There are reasons to suspect that CO2–embolisation could be the reason due to the liver structure with many large low pressure veins that could remain open after the incision into the hepatic parenchyma. Different methods to detect embolisation have been used, such as measurements of en-tidal CO2, mean pulmonary arterial pressure, the use of transesofageal echocardiography or auscultation.
Questions: Can different interventions of the anaesthesiologist or surgeon have an impact of the risk for embolisation? How can we detect gas embolisation with the monitoring techniques used today? Will the surgical technique influence bleeding and gas embolisation during laparoscopic liver resection?
Methods and results: Experimental studies are performed in anesthetized pigs instrumented with catheters for measurements of hemodynamic and respiratory parameters, on-line arterial blood gas analysis and blood sampling. To detect venous embolisation, transesofageal echocardiography will be used to visualize the rights side of the heart. Four studies have already been performed where a certain amount of CO2 has been injected into the blood circulation to detect and follow changes in hemodynamic and respiratory variables during the following four hours. We have developed a method to quantify the degree of embolisation with transesofageal echocardiography. We have also shown that early detection of gas embolisation can be done with on-line measurements of arterial blood gases.
Members of the group during 2013
Sten Rubertsson, Professor
Dag Arvidsson, Associate Professor, MD, PhD
Diddi Fors, MD, PhD student
Kristin Eiriksson, PhD student
Coordinator: Miklós Lipcsey
Septic shock is commonly called blood poisoning. In this condition bacteria, fungi or viruses enter the bloodstream and cause an infection with major impact on the body, including inflammation, disturbed blood circulation, blood and tissue oxygenation and decreased level of consciousness. Septic shock is commonly seen in intensive care, and is associated with high mortality and is associated with high health care costs. Although septic shock may occur suddenly in previously healthy people, it is more common in people with multiple illnesses and underlying infections.
According to estimates, the intestines contain 1-2 kg of microbes. These potentially dangerous microorganisms are isolated from the circulation, where they could induce sepsis, through various barrier systems and the immune system. One of the mechanisms is probably that the circulation from the intestines passes the liver containing the body's largest amount of cells of the innate immune system through the mononuclear phagocytic system (MPS). Our hypothesis is that the MPS works less efficient in systemic inflammation as in blood poisoning, allowing microbes or their fragments to reach systemic circulation with activation / maintenance of the systemic inflammatory response. In an experimental model of blood poisoning, we investigate whether MPS function in systemic inflammation is actually depressed, and what parts of MPS are affected and also if there are pharmacological methods to affect the impaired function in MPS.
Members of the group 2018
Miklós Lipcsey, Principal Investigator, Associate Professor, Hedenstierna Laboratory, miklos.lipcsey@surgsci.uu.se, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Katja Hanslin, PhD student, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Anders Larsson, Professor, Clinical Chemistry, Department of Medical Sciences
Jan Sjölin, Professor, Infectious Diseases, Department of Medical Sciences
Patients in intensive care units have reversible failure in one or more organ systems. They also often have a several other chronic illnesses. Considering that intensive care is demanding for patients, and generates high costs for society, it is important that outcomes for patients are followed up after intensive care. One way to do this is through the Swedish Intensive Care Register that collects data from all general intensive care units in Sweden. The project investigates mortality, complications and quality of life after sepsis.
Members of the group
Miklós Lipcsey, Principal Investigator, Associate Professor, Hedenstierna Laboratory
Björn Ahlström, PhD student
Ing-Marie Larsson, PhD
Gunnar Strandberg, PhD
Mats Eriksson, Associate Professor
All above are affiliated to Anaesthesiology and Intensive Care, Department of Surgical Sciences.
The outcome of patients with severe infections is determined by whether correct antibiotics are administered quickly and in the correct dose. The effect of the right antibiotics at the right dose should be greatest during the first day, as the bacterial burden is greatest then. The knowledge about the pharmacokinetics of antibiotics is based on studies with healthy volunteers. Antibiotic concentration in the blood of critically ill patients is the first day is unknown. In the ACCIS study, blood samples have been collected from patients in 7 intensive care units. In addition to descriptive studies, data will be used for pharmacological models for optimal antibiotic dosing and development of bedside measurement of blood antibiotic concentration.
Members of the group 2018
Miklós Lipcsey, Principal Investigator, Associate Professor, Hedenstierna Laboratory, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Anna-Karin Smekal, PhD student, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Mia Furebring, PhD, Infectious Diseases, Department of Medical Sciences
Jan Sjölin, Professor, Infectious Diseases, Department of Medical Sciences
Elisabet Nilsen, Associate Professor, Pharmacometry, Department of Pharmaceutical Biosciences
Anders Larsson, Professor, Clinical Chemistry, Department of Medical Sciences
Treatment of severe infections is largely based on antibiotics today. With increasing antibiotic resistance problems, other treatment options are needed. After immunization of hens against bacteria, chicken eggs contain polyclonal antibodies against the bacterium with which immunization was done. This is a cheap and effective method of producing antibodies. In this project, we investigate antibodies against bacteria that cause severe and difficult to treat intensive care infections are evaluated in an experimental pneumonia model.
Members of the group 2018
Miklós Lipcsey, Principal Investigator, Associate Professor, Hedenstierna Laboratory, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Alexander Otterbeck, PhD student, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Anders Larsson, Professor, Clinical Chemistry, Department of Medical Sciences
Johan Stålberg, Immunsystems AB
Hans Hjelmqvist, Professor, Anesthesia and Intensive Care, Örebro University
Fluid treatment is one of the most common means of treatment during with surgery and in intensive care. The project investigates the factors that impact on fluid treatment, the effects of this treatment, and how restrictive fluid therapy affects the physiology of patients after surgery and in intensive care.
Members of the group
Miklós Lipcsey, Principal Investigator, Associate Professor, Hedenstierna Laboratory
Sandra Horst, PhD student
Raphael Kawati, PhD
Egidijus Semenas, PhD
All above are affiliated to Anaesthesiology and Intensive Care, Department of Surgical Sciences.
With life-threatening injuries, especially in children, creating access to the bloodstream can be challenging, and when such accesses are obtained fluid infusions are prioritized. Getting blood samples is of course also very important in the acute situation. Obtaining clinically relevant blood samples for laboratory analysis quickly and thereby being able to initiate adequate therapy can be lifesaving in for these severely ill patients. Special needles, so-called intraosseous needles, can be drilled into the marrow in bones and used for fluid substitution, drug delivery and sampling. Unfortunately, there is a widespread misconception that intraosseous needles are not suitable for sampling because the samples contain bone marrow particles which can damage the analytical instruments. Since laboratory technology has developed, analyses can be performed bedside and intraosseous samples can now be analysed in a cuvette that does not come into direct contact with the assay instrument, the method of sampling from intravenous needles needs to be re-evaluated. Studies in this project investigate the reliability of samples taken from an intraosseous needle and also the reliability administration of drugs through an intraosseous needle.
Members of the group 2018
Mats Eriksson, Principal Investigator, Associate Professor, mats.eriksson@surgsci.uu.se, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Miklós Lipcsey, Associate Professor, Hedenstierna Laboratory, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Gunnar Strandberg, PhD, Anaesthesiology and Intensive Care, Department of Surgical Sciences
Anders Larsson, Professor, Clinical Chemistry, Department of Medical Sciences
Principle Investigator: Torbjörn Karlsson
Background: The scientific background and evidence for nutritional efforts after severe head trauma is weak, but observational studies show that many of these patients (68% in our material) suffer malnutrition according to specific criteria during the course of treatment. We have observed that this affects the rehabilitation of this group of patients.
We aim to explore the course of energy balance the first months after head injury and to develop a clinical method to measure and predict energy expenditure after traumatic brain injury.
We have used daily indirect calorimetry and the doubly labeled water technique to assess energy expenditure in a group of TBI patients. We are using repeated CT scans to study the effects on muscle and fat catabolism and preliminary results show different effects on peripheral fat and intraabdominal fat deposits, while muscular catabolism seem to be more general.
SAH can give rise to an intracerebral metabolic crisis and we have observed that changes in the blood glucose by insulin injection (aiming at a tight glucose control) might give rise to a potentially to low intracerebral glucose concentration. We have also observed an increased level of non-transmittor amino acids 3-4 days after the onset of SAH, with a difference between non-awake patients with less affected consciousness. Possibly as a result of the intracerebral repair process.
Questions: What is the EE in the acute phase after SAH and how does it change over time?Is there a relation between EE and the severity of SAH as measured with Fisher, WFNS and the development of delayed ischemic neurologic deficits? Is there a relation between EE and the brains metabolism as measured with intracerebral microdialysis?Is there a relation between the EE, the endocrinological reactions and systemic complications?Is there a relation between the EE and the cerebral blood flow as measured with Xe-enhanced CT?
We are using clinical data, hormonal analyses, intracerebral microdialys and general hemodynamic monitoring completed with indirect calorimetry and radiology to answer the above questions. Preliminary results from an ongoing study (n 83 SAH patients) show increased p-NT-proBNP after SAH, probably both from the heart and the brain, and, the results indicate that p-NT-proBNP could be used as a marker of more severe SAH disease.
Members in the group 2013
Torbjörn Karlsson, MD, PhD
Elisabeth Ronne-Engström, MD, PhD
Jörgen Borg, Professor Karolinska Intitutet
Karolina Krakau, RN, PhD
Maria Zetterling, MD, PhD
Christoffer Nyberg, MD, PhD student
In collaboration with
Anders Magnusson, Professor Radiology Uppsala
Lars Ellegård, MD, PhD Gothenburg
Dissertations during 2012
Kristinn Eiriksson
Diddi Fors
Emma Pontén
László Vimláti
Elisabet Nilsen, Associate Professor, Pharmacometry, Department of Pharmaceutical Biosciences
