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>

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.

<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.

Introduction. Multiple clinical methods for detecting myocardial ischemia are utilised in the hospital setting each day, but there is uncertainty about their diagnostic accuracy. In the operating room, multiple methods may be employed, while in the CCU advanced electrophysiological (ECG) techniques for myocardial ischemia detection, and in particular, ST segment analysis, are common. Vectorcardiography (VCG) is one form of ECG. Several conditions other than ischemia may cause marked ST changes, which can impair the process of diagnosis of clinical ischemia. Elevated HR is one of these factors, which is studied here. The hypotheses were about concordance of different methods to detect ischemia, and relation of ECG ST levels to HR with and without myocardial ischemia. Methods. Study I. Anesthetised vascular surgical patients with coronary artery disease were studied during the start of anesthesia and surgery: ECG, hemodynamic, mechanical, and metabolic parameters were measured and categorised as positive or negative with reference to a specific definition of myocardial ischemia. Study II. Awake patients with no ischemic heart disease were paced in graded steps, and VCG ST analyses were performed. Study III. Anesthetised pigs were studied for local metabolic and VCG ST changes related to controlled HR levels and transient coronary occlusion. Study IV. Thirty five anesthetised coronary artery disease (CAD) patients and ten non-CAD patients were paced at controlled levels, and great coronary artery vein (GCV) lactate measurement was used to determine presence or absence of myocardial ischemia. The CAD patients were paced up to HR levels where myocardial ischemia could be confirmed. The relation of HR-related VCG ST levels to presence or absence of ischemia was analysed. In Studies II,, III, and IV the ST vector magnitude (ST-VM), the change from baseline in ST-VM (STC-VM), and the vector angle change from baseline (STC-VA) were analysed for each step. Results. Study I. Poor concordance was demonstrated for positive events (presumed myocardial ischemia) between the hemodynamic, ECG, mechanical, and metabolic detection methods. Study II. STC-VM but not ST-VM levels demonstrated HR-related increases in the presumed absence of myocardial ischemia in 18 awake subjects. J point time to ST measurement did not affect the response of VCG ST to HR. Study III. STC-VM levels showed HR-related increases in the absence of ischemia (tested by local metabolic observations). VCG ST parameters responded positively to transient regional ischemia. Study IV. CAD patients, which demonstrated a clear pattern of onset and progress of ischemia during pacing, were further analysed for the relation of VCG ST level to ischemia. Sensitivity and specificity of STC-VM levels were described by ROC analysis for a range of STC-VM levels. Conclusions. Concordance of different measures for detection of onset of myocardial ischemia is difficult to assess in the absence of a very reliable reference method. The contribution of HR and ischemia to VCG ST levels were estimated in study subjects. HR-related increases in STC-VM occur in the absence of ischemia. HR levels need to be considered when interpreting STC-VM as a diagnostic test for ischemia. Further study is needed to establish criteria that take into account multiple clinical factors in order to improve the predictive value of our tests for myocardial ischemia.

Det övergripande syftet med avhandlingsarbetet är att illustrera och belysa upplevelsen av att vara patient med behov av ledprotes, avseende aspekterna kommunikation, smärtupplevelse, lidande och tillfredsställelse med vård och behandling. Under väntetiden för ledprotesoperation upplever deltagarna i studierna lidande i olika former, tillika att vården är otillgänglig och onåbar i ett ansiktslöst system (I). Att få information om sin sjukdom vad man kan/får/ska göra är nästan omöjligt. Kontakten med sjukvården är svår att upprätta och det är mestadels patientens ansvar att söka information om vad som händer (II). Den bristfälliga kommunikationen som deltagarna i delstudie I upplever, leder till att de känner sig missförstådda och nedvärderade av sjukvårdssystemet, och därmed befinner sig i en ständig kamp för att få sitt vårdbehov bekräftat. Under deltagarnas vandring i sjukvårdssystemet förändras deras negativa uppfattning om vården till att bli mer positiv när en reell kommunikation och personlig kontakt etablerats (IIV). Fynden i arbetena (I-IV) tolkas inom ramen för Katie Erikssons och Lennart Fredrikssons beskrivningar av lidande och det vårdande samtalet. En del deltagare i studierna har av egen kraft, eller till följd av personliga egenskaper uppnått insikter om sig själva och försonats med sitt lidande, på så sätt har de kunnat bibehålla eller uppnå mening i sin tillvaro. Av egen kraft, eller med hjälp av anhöriga kan individerna få sitt lidande bekräftat och därmed möjligheten att kunna lida ut och försonas med sig själv och den förändrade tillvaron. Så länge som sjukvården upplevs som ett ansiktslöst system finns det deltagare i avhandlingen som inte klarar av att ta itu med sitt lidande. Under patientens vandring i sjukvårdssystemet blir det uppenbart att systemet får ett ansikte först när deltagarna kan relatera till vården i form av en reell person. Vården får inte ett ansikte så länge som patienten upplever sig dåligt bemött utan detta sker när det med Fredrikssons termer uppstår ett vårdande samtal. Under väntetiden för operation finns det relativt få tillfällen där ett vårdande samtal har möjlighet att uppstå. Möjligheten för detta är dock större när patienten väl är inlagd på sjukhuset för att bli opererad, vilket återspeglas i den höga grad av tillfredsställelse med vården som uttrycks i delstudie II-IV. Patienterna är tillfredsställda med vård och behandling, trots att de har upplevt postoperativ smärta i en hög grad. I delstudie III var det 68% (n=40) och i delstudie IV 83.5% (n=50) som hade upplevt smärtor motsvarande ≥ 4 på Visuell Analog Skala (VAS). Under sjukhusvistelsen upplever sig patienten bekräftad och synlig i systemet. Synligheten är ömsesidig då även vården (systemet) får ett ansikte på patienten. I ett vårdande samtal uppstår en känsla av tillit och när detta sker vågar patienten och vårdaren kommunicera på ett öppet sätt där de båda är närvarande i situationen / The overall objective of the thesis is to describe and illustrate the experience of being an arthroplastic surgery patient during the perioperative period with regard to the issues of communication, pain,suffering and satisfaction with care. While waiting for surgery, the participants in this thesis experience suffering in different ways and mainly experience health care as being unavailable and negative in a faceless system (I). Obtaining information related to their illness is difficult, as it is hard to establish contact with health care providers. The responsibility for establishing contact and obtaining information rests solely with the patients (II). In Paper I, due to poor communication, the respondents express feelings of abandonment, anonymity and being disparaged by the health care system. During the participants' journey through the health care system, the negative experience acquires a more positive nature, as personal contacts are established with health care representatives (I-IV). The findings in the different papers (I-IV) are interpreted in the light of Katie Eriksson and Lennart Fredriksson’s descriptions of suffering and the caring conversation. There are participants in this thesis who have been able to reach a personal understanding of themselves and have found reconciliation in suffering. In this way, they have been able to maintain or obtain meaning in their lifeworld. Through their own power, or with the help of family and friends, individuals may be able to attain confirmation of their suffering, have the time and space to suffer and find reconciliation. However, as long as health care is experienced as a faceless system, there are individuals in this study who are unable to face their suffering. During the patients’ journey through the system, it becomes obvious that the system obtains a face when the individuals are able to establish trustful contact with an actual person within the system. The system does not obtain a face as long as the individuals perceive themselves as being poorly treated by health care representatives. In these cases, the system is actually the cause of additional suffering. In the terms defined by Fredriksson, the system obtains a face when a turning point occurs in the form of a caring conversation. During the waiting time, there are few opportunities for a caring conversation. An opportunity is more likely to occur when the individual is admitted to hospital. This is reflected in the extensive degree of satisfaction with care as expressed in Papers II-IV. High levels of satisfaction are reported, although the participants report having experienced high levels of postoperative pain. In Paper III, 68% (n=40) and, in Paper IV, 83.5% (n=50) of the patients experienced pain of ≥ 4 on the Visual Analogue Scale (VAS). When they have been admitted to hospital, the individuals sense that they are confirmed by and visible in the system. This visibility is mutual, as the individual becomes an actual person to health care representatives. In a caring conversation, a sense of trust is established and, as this occurs, the individual and the care provider dare to communicate in an open way, where both are present in the situation.

<p>Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC).</p><p>In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow.</p><p>Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC.</p><p>Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC.</p><p>By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC. </p><p>In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor. </p>

<p>Evaluating respiratory mechanics during dynamic conditions without interrupting ongoing ventilation and flow, adds to the information obtained from the mechanics derived from static (= no flow) conditions, i.e., the flow signal has the potential to provide information on the properties of the respiratory system (including the tubing system). Hence monitoring the changes in the flow signal during ongoing mechanical ventilation would give information about the dynamic mechanics of the respiratory system. Any change in the mechanics of the respiratory system including the endotracheal tube (ETT) and the ventilatory circuit would affect the shape of the flow signal. </p><p>Knowledge of the airway pressure distal to the ETT at the carina level (= tracheal pressure) is required for calculating the extra resistive load exerted by the endotracheal tube in order to compensate for it. In a porcine model, the flow signal was used to non-invasively calculate tracheal pressure. There was good agreement between calculated and measured tracheal pressure with different modes of ventilation. However, calculation of tracheal pressure assumes that the inner diameter of the ETT is known, and this assumption is not met if the inner diameter is narrowed by secretions. Flow that passes a narrowed tube is decelerated and this is most pronounced with the high flow of early expiration, yielding a typical time constant over expiratory volume pattern that is easy to recognize during mechanical ventilation. This pattern reliably detected partial endotracheal obstruction during volume and pressure controlled mechanical ventilation. </p><p>A change in compliance of the respiratory system modifies the elastic recoil and this also affects the rate of the expiratory flow and the shape of its signal. In a porcine model, lung volume gains on the flow signal generated by the heartbeats (cardiogenic oscillations) provided information about the compliance of the respiratory system during ongoing mechanical ventilation</p><p>In conclusion analyzing the flow signal during ongoing ventilation can be a cheap, non-invasive and reliable tool to monitor the elastic and resistive properties of the respiratory system including the endotracheal tube.</p>

Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC). In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow. Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC. Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC. By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC. In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor.