Hypothermia treatment with cooling to a body temperature of 32-34°C has been shown to be an effective way of improving neurological outcome and survival in unconscious patients successfully resuscitated after cardiac arrest (CA). The method is used clinically but there are still many questions on the biological mechanisms and on how the treatment is best performed. This thesis focuses on cerebral and haemodynamic effects of hypothermia and rewarming. A porcine model of CA was used. To shorten time to reach target temperature, induction of hypothermia, by means of infusion of 4°C cold fluid, was started already during ongoing cardiopulmonary resuscitation. The temperature was satisfactorily reduced without obvious haemodynamic disturbances. Cerebral effects of hypothermia and rewarming were studied. Microdialysis monitoring showed signs of cerebral energy failure (increased lactate/pyruvate-ratio) and excitotoxicity (increased glutamate) immediately after CA. There was a risk of secondary energy failure that was reduced by hypothermia. Intracranial pressure (ICP) increased gradually after CA irrespectively of if hypothermia was used or not. There were no indications of increasing cerebral disturbances during rewarming. Haemodynamic effects of hypothermia treatment and rewarming were examined in a study of patients successfully resuscitated after CA. Hypothermia was induced by means of cold intravenous infusion. No negative effects on the cardiovascular system were revealed. There were indications of decreased intravascular volume in spite of a positive fluid balance. Cerebral microdialysis and ICP recording were performed in four patients. All patients had signs of energy failure and excitotoxicity following CA. ICP was only exceptionally above 20 mmHg. In contrast to the experimental study indications of increasing ischemia were seen during rewarming. Glycerol had a biphasic pattern, perhaps due to an overspill of metabolites from the general circulation. As most patients become extensively anti-coagulated following CA, intracranial monitoring is not suitable to be used in routine care.

<p>Neuropathic pain of central and peripheral origin presents a substantial clinical problem as it is often resistant to pharmacological treatment.</p><p>The health related quality of life of 126 patients with peripheral neuropathic pain was studied, to provide a cross sectional description from this point of view. Two generic health-related quality of life instruments; the SF-36 and the Nottingham Health Profile were used together with pain assessments, global rating of health and verbal rating scales of pain and other symptoms, as well as patient descriptors.</p><p>The analgesic effect of ketamine, lidocaine and morphine were assessed in a double blind, placebo-controlled, randomized study design. Three groups of patients were studied: patients with peripheral neuropathic pain of traumatic origin, patients with central post-stroke pain and patients with neuropathic pain after spinal cord injury. Somatosensory function was examined to see if this could predict response to treatment and to investigate if the drugs caused changes in thermal or mechanical sensibility.</p><p>The results shows that the intense pain, limited efficacy and tolerability of available treatments, the low overall rating of health, reduced work status and troublesome symptoms constitute a substantial impact on the quality of life for patients with peripheral neuropathic pain.</p><p>The NMDA-antagonist ketamine yielded substantial pain relief to patients with peripheral neuropathic pain and patients with neuropathic pain after spinal cord injury. However, the reported side effects limit the clinical usefulness of the treatment. Lidocaine did not give significant pain relief to the patients in the three studied groups. Morphine may represent a therapeutic alternative for some patients with central post-stroke pain, although only a small group of this category of patients responded with analgesia.</p><p>Assessment of baseline somatosensory functions could not be used to identify responders to treatment with either drug, nor did ketamine, lidocaine or morphine cause any changes in thermal or mechanical sensibility.</p>

Background:     The microdialysis (MD) technique is widely spread and used both experi­mentally and in clinical practice. The MD technique allows continuous collection of small molecules such as glucose, lactate, pyruvate and glycerol. Samples are often analysed using the CMA 600 analyser, an enzymatic and colorimetric analyser.  Data evaluating the performance of the CMA 600 analysis system and associated sample han­dling are sparse. The aim of this work was to identify sources of variability related to han­dling of microdialysis samples and sources of error associated with use of the CMA 600 analyser. Further, to develop and compare different application techniques of the micro­dialysis probes both within an organ and on the surface of an organ.  Material and Methods:  Papers I and II are mainly in vitro studies with the exception of the No Net Flux calibration method in paper I where a pig model (n=7) was used to exam­ine the true concen­tration of glucose and urea in subcutaneous tissue. Flow rate, sampling time, vial and caps material and performance of the analyser device (CMA 600) were examined. In papers III and IV normoventilated anaesthetised pigs (n=33) were used. In paper III, heart ischemia was used as intervention to compare microdialysis measurements in the myocardium with corresponding measurements on the heart surface. In paper IV, microdialysis measurements in the liver parenchyma were compared with measurements on the liver surface in associa­tion with induced liver ischemia. All animal studies were approved by the Animal Experi­mental Ethics Committee at Umeå University Sweden. Results:  In paper I we succeeded to measure true concentrations of glucose (4.4 mmol/L) and Urea (4.1 mmol/L) in subcutaneous tissue. Paper II showed that for a batch analyse of 24 samples it is preferred to store microdialysis samples in glass vials with crimp caps. For reliable results, samples should be centrifuged before analysis. Paper III showed a new application area for microdialysis sampling from the heart, i.e. surface sampling. The sur­face probe and myocardial probe (in the myocardium) showed a similar pattern for glucose, lactate and glycerol during baseline, short ischemic and long ischemic interventions. In paper IV, a similar pattern was observed as in paper III, i.e. data obtained from the probe on the liver surface showed no differences compared with data from the probe in liver paren­chyma for glucose, lactate and glycerol concentrations during baseline, ischemic and reperfusion interven­tions. Conclusion:  The MD technique is adequate for local metabolic monitoring, but requires methodological considerations before starting a new experimental serie. It is important to consider factors such as flow rate, sampling time and handling of samples in association with the analysis device chosen. The main finding in this thesis is that analyses of glucose, lactate and glycerol in samples from the heart surface and liver surface reflect concentra­tions sampled from the myocardium and liver parenchyma, respectively.

Despite increasingly sophisticated perioperative management, cardiovascular complications continue to be major challenges for the clinician. As a growing number of elderly patients with known coronary artery disease (CAD) or with risk factors for CAD are undergoing non-cardiac surgery, cardiovascular complications will remain a significant clinical problem in the future. The overall objective of this thesis was to study the incidence of myocardial damage and perioperative adverse cardiac events, to determine predictors of poor outcome and to assess the effect of a medical intervention in patients at risk undergoing non-cardiac surgery. The studies in this thesis were conducted on a total of 952 patients undergoing non-cardiac surgery. Studies I and IV were multicenter studies; whereas the patients included in studies II and III underwent non-cardiac surgery at Linkoping University Hospital, Sweden. The correlation between postoperative myocardial damage and short- and long-term outcome were studied in 546 patients, aged 70 years or older undergoing non-cardiac surgery of at least 30 minutes duration. This study showed a close correlation between postoperative myocardial damage and poor short- as well as long-term outcome. Elevated Troponin T was a strong independent predictor of mortality within one year of surgery. In 186 patients with ASA physical status classification III or IV undergoing non-elective surgery, the incidence of myocardial damage was 33%. In this study preoperative myocardial damage was an independent predictor of major adverse cardiac events in the postoperative period. In 69 patients with ASA physical status classification III &amp; IV undergoing acute hip surgery, we found a close correlation between elevated NT-proBNP value prior to surgery and cardiac complications in the postoperative period. To study the effect of acetylsalicylic acid on postoperative myocardial damage and cardiovascular events, 220 patients at risk were randomized to receive 75 mg of acetylsalicylic acid or placebo 7 days prior to surgery until the third postoperative day. This study showed that treatment with acetylsalicylic acid resulted in an 8% (95% CI 1-15%) absolute risk reduction of having a postoperative major adverse cardiac event. No statistically significant differences of bleeding complications were seen between the groups. In conclusion, this thesis contributes to the understanding of the clinical relevance of elevated cardiac markers (with or without clinical or ECG signs of myocardial damage) in patients undergoing elective or emergency surgery. Moreover, we have identified predictors of poor outcome in the perioperative period that could be used as tools for identifying patients at risk. Finally, we have shown that continuing acetylsalicylic acid in the perioperative period reduced the risk of major adverse cardiac events within 30 days of surgery.

Neuropathic pain of central and peripheral origin presents a substantial clinical problem as it is often resistant to pharmacological treatment. The health related quality of life of 126 patients with peripheral neuropathic pain was studied, to provide a cross sectional description from this point of view. Two generic health-related quality of life instruments; the SF-36 and the Nottingham Health Profile were used together with pain assessments, global rating of health and verbal rating scales of pain and other symptoms, as well as patient descriptors. The analgesic effect of ketamine, lidocaine and morphine were assessed in a double blind, placebo-controlled, randomized study design. Three groups of patients were studied: patients with peripheral neuropathic pain of traumatic origin, patients with central post-stroke pain and patients with neuropathic pain after spinal cord injury. Somatosensory function was examined to see if this could predict response to treatment and to investigate if the drugs caused changes in thermal or mechanical sensibility. The results shows that the intense pain, limited efficacy and tolerability of available treatments, the low overall rating of health, reduced work status and troublesome symptoms constitute a substantial impact on the quality of life for patients with peripheral neuropathic pain. The NMDA-antagonist ketamine yielded substantial pain relief to patients with peripheral neuropathic pain and patients with neuropathic pain after spinal cord injury. However, the reported side effects limit the clinical usefulness of the treatment. Lidocaine did not give significant pain relief to the patients in the three studied groups. Morphine may represent a therapeutic alternative for some patients with central post-stroke pain, although only a small group of this category of patients responded with analgesia. Assessment of baseline somatosensory functions could not be used to identify responders to treatment with either drug, nor did ketamine, lidocaine or morphine cause any changes in thermal or mechanical sensibility.

A substantial number of patients undergoing cardiac surgery are on dual anti-platelet treatment with clopidogrel and aspirin. A disadvantage with this treatment is increased risk of bleeding. Bleeding is a complication of major concern associated with adverse outcome for the patient and increased hospital resource utilization. Great variability in individual response to clopidogrel has been reported. If in vitro measurements of platelet reactivity would correlate with clinical bleeding parameters, potential bleeders could be identified preoperatively. The aims of this thesis were: (1) to describe the degree of pre-operative platelet inhibition in patients scheduled for primary isolated coronary artery bypass graft surgery; (2) to prospectively investigate whether the pre-operative platelet inhibition correlated with intra- and postoperative bleeding and transfusion requirements; and (3) to test the ability of clinically relevant risk factors to predict re-exploration for bleeding. (4) In addition, a cost analysis was performed on patients re-explored for bleeding, to analyse the magnitude of added resource utilization and costs. Based on this, a cost model of prophylactic treatment with haemostatic drugs was calculated. Platelet function tests investigated were: (1) flow cytometry, (2) VASP, (3) VerifyNowSystem, (4) PlateletMapping (a modified TEG), and (5) PFA-100. Clinical risk factors for re-exploration and the influence of antiplatelet and antifibrinolytic therapy were evaluated in a retrospective analysis. Cost analysis at three cardiothoracic centres was performed in a case-control study. In conclusion, there was no clinically useful correlation between preoperative assessment of platelet inhibition and blood loss or transfusion requirements during coronary artery bypass surgery. Furthermore, there was only modest agreement between the methods evaluating ADP-receptor blockade. Pre-operative treatment with the P2Y12-receptor inhibitor clopidogrel was an essential risk factor for re-exploration due to bleeding. Except for clopidogrel, no strong clinical factor to predict the risk of re-exploration was identified. The resource utilisation costs were 47% higher in patients requiring re-exploration due to bleeding than in those not requiring re-exploration. Prolonged stay in the ICU and recovery ward accounted for half of the added cost, a third was due to the costs of surgery, one fifth due to increased cost of transfusions, and &lt;2% was due to haemostatic drug treatment.

Background: Loading conditions are recognized to influence ventricular function according to the Starling relationship for length/stretch and force.  Many modern echocardiographic parameters which have been announced as describing ventricular function and contractile status, may be confounded by uncontrolled and unmeasured load.  These studies aimed to measure the relation between four differ­ent types of assessments of ventricular dysfunction and degrees of load.  Study examined the ‘myo­cardial performance index’ (MPI).  Study II examined long axis segmental mechanical dyssynchrony.  Study III examined tissue velocities, and Study IV examined ventricular twist.  All studies aimed to describe the relation of these parameters both to load and to inotropic changes. Methods:  In anesthetized juvenile pigs, left ventricular (LV) pressure and volume were measured continuously and their relationship (LVPVR) was analysed.  Preload alterations were brought about by inflation of a balloon tipped catheter in the inferior vena cava (IVCBO).  Inotropic interventions were brought about by either an overdose of anesthetic (combine intravenous pentobarbital and inhaled isoflurane, Study I), or beta blocker and calcium channel blocker given in combination (Stud­ies III and IV).  In one study (II), global myocardial injury and dysfunction was induced by endotoxin infusion.  MPI measurements were derived from LVPVR heart cycle intervals for isovolumic contrac­tion and relaxation as well as ejection time.  Long axis segmental dyssynchrony was derived by ana­lyzing for internal flow and time with segmental dyssynchronous segment volume change during systole, hourly before and during 3 hours of endotoxin infusion.  Myocardial tissue velocities were measured during IVCBO at control, during positive and then later negative inotropic interventions.  The same for apical and base circumferential rotational velocities by speckle tracking.  Load markers (including end-diastolic volume) were identified for each beat, and the test parameters were analysed together with load for a relation.  The test parameters were also tested during single apneic beats for a relation to inotropic interventions. Results: MPI demonstrated a strong and linear relationship to both preload and after-load, and this was due to changes in ejection time, and not the isovolumic intervals.  Long axis segmental dyssyn­chrony increased during each hour of endotoxin infusion and global myocardial injury.  This dysyn­chrony parameter was independent of load when tested by IVCBO. Peak systolic velocities were strongly load-independent, though not in all the inotropic situations and by all measurement axes.  Peak systolic strain was load-dependent, and not strongly related to inotropic conditions.  Peak sys­tolic LV twist and untwist were strongly load-dependent. Conclusions: MPI is strongly load-dependent, and can vary widely in value for the same contractile status if the load is varied.  Mechanical dyssynchrony measures are load-independen in health and also in early global endotoxin myocardial injury and dysfunction.  Peak sytole velocities are a clinically robust parameter of LV regional and global performance under changing load, though peak systolic strain seems to be load-dependent.  Left ventricular twist and untwist are load-dependent in this pig model.

<p>Succinylcolin är ett icke-depolariserande muskelrelaxantia som används inom anestesisjukvård. En vanlig biverkning är postoperativ myalgi. Varför smärtan uppstår är inte helt klarlagd. Under många år har forskare runt om i världen försökt komma till rätta med problemet utan att helt lyckas.Olika läkemedel och strategier har prövats. En av de viktigaste uppgifter en sjuksköterska har är att förebygga och lindra lidande. Som anestesisjuksköterska finns det möjlighet att påverka den vård som ordineras. Syftet med studien var att undersöka vilka metoder som kan förebygga postoperativ myalgi orsakad av succinylcolin. En litteraturstudie baserad på tio vetenskapliga artiklar genomfördes. Resultatet visade att parecoxib preoperativt samt premedicinering med diklofenakplåster gav det bästa resultatet när det gäller reducerande av myalgi. Med hjälp av dessa så vanliga läkemedel kan onödigt lidande förebyggas och samhällsekonomiska resurser sparas.</p><p> </p>

<p>Transesophageal echocardiography (TEE) has become a useful tool in monitoring the heart in patients during open-heart surgery. This study was undertaken to evaluate whether it is feasible to use TEE to assess left ventricular myocardial viability in anesthetized patients scheduled for coronary artery bypass grafting (CABG).</p><p>A total of 84 patients were studied. To test myocardial viability, TEE and a low-dose dobutamine stress regimen were used. Echocardiographic data were analyzed off-line using a visual or semiautomatic analysis of segmental left ventricular wall motion (LVWM). Visual assessment was performed by readers blinded to the sequence of events. The agreement between readers in visual analysis of segmental LVWM in the transgastric short-axis view was 73% or higher. Segmental LVWM assessed by TEE was compared to hemodynamic data obtained by thermodilution pulmonary artery catheter (PAC) and coronary angiographic data. Also, using the same low-dose dobutamine stress regimen, TEE findings in the anesthetized patient perioperatively were compared with preoperative transthoracic echocardiography (TTE) findings in the awake patient.</p><p>TEE was found to be feasible and adequate for testing left segmental ventricular viability. A concomitant increase in stroke volume assessed by PAC and decrease in LVWM-score assessed by TEE was found with dobutamine stimulation. Abnormal segmental LVWM corresponded to angiographically stenosed supplying coronary artery vessels. During dobutamine stimulation, 69% of the corresponding segments responded which is a sign of viability. The LVWM response to preoperative TTE and perioperative TEE dobutamine stress was comparable except for a significant difference in the apical segments.</p><p>This study showed that perioperative TEE dobutamine stress could be used to test left ventricular viability and was also a valuable supplement to PAC, angiography and TTE. The acquired knowledge is important and suggest that further development of transesophageal ultrasound technology is warranted.</p>

Transesophageal echocardiography (TEE) has become a useful tool in monitoring the heart in patients during open-heart surgery. This study was undertaken to evaluate whether it is feasible to use TEE to assess left ventricular myocardial viability in anesthetized patients scheduled for coronary artery bypass grafting (CABG). A total of 84 patients were studied. To test myocardial viability, TEE and a low-dose dobutamine stress regimen were used. Echocardiographic data were analyzed off-line using a visual or semiautomatic analysis of segmental left ventricular wall motion (LVWM). Visual assessment was performed by readers blinded to the sequence of events. The agreement between readers in visual analysis of segmental LVWM in the transgastric short-axis view was 73% or higher. Segmental LVWM assessed by TEE was compared to hemodynamic data obtained by thermodilution pulmonary artery catheter (PAC) and coronary angiographic data. Also, using the same low-dose dobutamine stress regimen, TEE findings in the anesthetized patient perioperatively were compared with preoperative transthoracic echocardiography (TTE) findings in the awake patient. TEE was found to be feasible and adequate for testing left segmental ventricular viability. A concomitant increase in stroke volume assessed by PAC and decrease in LVWM-score assessed by TEE was found with dobutamine stimulation. Abnormal segmental LVWM corresponded to angiographically stenosed supplying coronary artery vessels. During dobutamine stimulation, 69% of the corresponding segments responded which is a sign of viability. The LVWM response to preoperative TTE and perioperative TEE dobutamine stress was comparable except for a significant difference in the apical segments. This study showed that perioperative TEE dobutamine stress could be used to test left ventricular viability and was also a valuable supplement to PAC, angiography and TTE. The acquired knowledge is important and suggest that further development of transesophageal ultrasound technology is warranted.