Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009.

Bakgrund: Thorax- och bukoperationer utförs under generell anestesi. En minskning av FRC och utveckling av atelektaser kan ses som följd av anestesibehandlingen. Fysioterapeutisk andningsgymnastik är en del av den postoperativa vården för att förebygga och minska komplikationer. Vanligt förekommande metoder för att förbättra respirationen och minska komplikationsrisken är tidig mobilisering, djupandningsövningar och djupandningsträning mot motstånd på utandningen, PEP. Följsamhet till en ordinerad behandling är av högsta vikt för att det önskvärda resultatet ska uppnås. Syfte: Syftet med studien var att undersöka patienters upplevelse av vad som påverkar deras följsamhet till postoperativ behandling med PEP. Metod: Kvalitativ deskriptiv design med semistrukturerade intervjuer. Fem patienter som fått PEP ordinerat efter operationen inkluderades i studien. Analysmetoden som användes var en kvalitativ innehållsanalys med induktiv ansats. Resultat: Analysen resulterade i fem kategorier: Preoperativ information, Måendet efter operationen, Tankar om PEP, Stöd till att andningsträna och Effekter av PEP. Slutsats: Med ett beteendemedicinskt perspektiv går det att se hur utfallsförväntningar, self-efficacy, kompetens, autonomi och tillhörighet har påverkat deltagarnas följsamhet till andningsträning.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2009.

Introduction An increasing proportion of the patients undergoing cardiac surgery have diabetes mellitus, in particular type II diabetes. In spite of this, diabetic patients have received limited attention in this setting. Although diabetes is a metabolic disease cardiac metabolism in association with surgery has previously not been explored in diabetics. This investigation was carried out to describe the metabolic state of the heart in diabetics after cardiac surgery and to study if it is accessible to metabolic intervention with high-dose GIK. Also, the potential hazards associated with such a regime in clinical practice were evaluated. Furthermore, a comparison of the outcome in diabetic and nondiabetic patients after coronary surgery was done. Methods Myocardial metabolism and how it was influenced by high-dose GIK was assessed with coronary sinus catheter technique in a prospective randomized study on 20 type II diabetic patients undergoing CABG (paper I, II). Safety issues concerning high-dose GIK were assessed in two retrospective studies. The potential role of metabolic interventions for neurological injury was assessed in a cohort of 775 consecutive patients undergoing CABG or combined CABG + valve surgery, in whom metabolic interventions gradually replaced traditional treatment for postoperative heart failure (paper III). A detailed analysis of blood glucose and electrolyte control was done in all cases (n=89) receiving high-dose GIK during one year (paper IV). The hemodynamic impact of highdose GIK was assessed with standard postoperative monitoring including Swan-Ganz catheters (paper II, IV). Outcome and prognosis after CABG in diabetic patients (n=540) were compared with nondiabetics (n=2239) with the aid of the institutional database comprising all isolated CABG procedures from 1995-1999 (paper V). Results The metabolism of the diabetic heart after CABG was characterized by predominant uptake of FFA and restricted uptake of carbohydrate substrates. A high extraction rate of beta-hydroxybutyric acid and glutamate was also found. Alanine was released from the heart (paper I). High-dose GIK induced a shift towards uptake of carbohydrates, in particular lactate, at the expense of FFA and betahydroxybutyric acid (paper II). A substantial systemic glucose uptake was found during high-dose GIK treatment but the uptake tended to be lower and blood glucose higher if adrenergic drugs were used or/and if the patient was a diabetic (paper IV). High-dose GIK was associated with beneficial effects on cardiac output both in the prospective and retrospective analyses (paper II, IV). No evidence for untoward neurological effects associated with GIK treatment was found. History of cerebrovascular disease was the most important risk factor for postoperative cerebral complications and in general markers for advanced atherosclerotic disease were found to be of importance (paper III). High-dose GIK in clinical practice was associated with acceptable blood glucose and electrolyte control and no serious adverse events were recorded (paper IV). Patients with diabetes undergoing CABG had an acceptable short-term mortality that did not differ significantly from non-diabetic patients. However, diabetic patients had a higher early postoperative morbidity particularly with regard to stroke, renal- and infectious complications. Also, long-term survival was markedly reduced in diabetic patients, particularly in insulin treated patients (paper V). Comments FFA were the main source of energy for the heart in type II diabetics after CABG whereas the uptake of carbohydrates was restricted. The high extraction rates of beta-hydroxybutyric acid and glutamate may represent an adaptation to the unfavorable metabolic situation of the post-ischemic diabetic heart. High-dose GIK can be used in type II diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of FFA and beta-hydroxybutyric acid. The magnitude of this shift was sufficient to account for the entire myocardial oxygen consumption assuming that the substrates extracted were oxidized. This could have implications for the treatment of the diabetic heart in association with surgery and ischemia. Provided careful monitoring high-dose GIK can be safely used in clinical practice and this treatment deserves further evaluation in the treatment of postoperative heart failure. High-dose GIK also provides a means for strict blood glucose control and as substantial amounts of glucose can be infused even in critically ill patients, it may prove useful for nutrition in critical care. Several of the risk factors for neurological injury identified constitute markers for advanced atherosclerotic disease, thus, also providing an explanation for the increased risk of neurological injury in diabetics after cardiac surgery. Short-term mortality was acceptable in diabetics after CABG. However, further efforts are warranted to address postoperative morbidity and late outcome. This represents a challenge as diabetic patients are accounting for an increasing proportion of the patients undergoing CABG. / On the day of the public defence the status of article IV was: Submitted and the title of article IV was in the printed version: High-dose GIK in cardiac surgery - clinical safety issues and lessons learned.

Chronic aortic regurgitation (AR) of varying degree affects 13% of men and 8.5% of women. In persons with severe AR, the expected length of life and its quality are influenced. Some individuals remain asymptomatic for a long period, due to effective compensatory mechanisms, but dysfunction of the left ventricle (LV) usually begins before symptoms appear and can be irreversible by then. This thesis addresses questions of LV function and optimal time for operation of patients suffering from chronic AR. Moreover, detailed echocardiographic studies of the anatomy of the normal aortic valve have been performed to obtain a better understanding of the in vivo anatomic relations within the aortic root. Patients with chronic AR, without concomitant cardiac disease, were studied both retrospectively (n=88) and prospectively (n=29) and the aortic valves of persons (n=32) free from cardiac disease were investigated. For the retrospectively studied patients, survival was 82% at 10 years which is an improvement compared with previously published results. The majority of the patients, however, had LV dysfunction preoperatively. By studying patients prospectively by echocardiography, radionuclide ventriculography (MUGA) and cardiopulmonary exercise testing (CPET) our aim was to evaluate the predictive value of measurements of LV function at rest and during exercise for postoperative outcome. LV diameters were markedly elevated prior to and diminished significantly after surgery. Patients with an abnormal exercise ejection fraction (EF) response by MUGA preoperatively, presented the same reaction postoperatively. This could not be predicted by LV function determination at rest, or by NYHA functional class. In spite of median NYHA class II, these patients had a low work capacity on CPET, which was neither improved 6 months postoperatively nor correlated to echocardiographic LV dimensions. Thus, both MUGA and CPET may be useful complements for timing of surgery in patients with chronic AR. Assuming that patients would benefit from preservation of their native valves the normal aortic valve was studied to gain detailed information about the echocardiographic anatomy and relations within the normal aortic root. This extended examination of the aortic root may facilitate a better planning of aortic valve‐preserving interventions in the future.

Introduction: Neurological complications and stroke in association with cardiac surgery is a serious problem. The stroke event can occur during surgery (early stroke) or in the postoperative period with a symptom free interval (delayed stroke). Particle embolization due to aortic manipulation during surgery has been suspected as a mechanism for early stroke. The present thesis address mechanisms and survival effects of stroke both clinically (I-III) and experimentally (IV-V). Methods: Study I) Within a cohort of 2641 consecutive cases, a group of cardiac surgery patients with stroke and evaluated by computed tomography (CT) were studied (n=77). CT-findings were analyzed in relation to stroke symptoms. Study II) Data from 9122 patients undergoing coronary surgery were analyzed. Records of patients with any signs of neurological complications were reviewed to extract 149 subjects with stroke at extubation (early, 1.6%) versus 99 patients having a free interval (delayed, 1.1%). Early and delayed stroke were evaluated separately. Independent risk factors for stroke were analyzed by logistic regression and survival by Cox regression (9.3 years median follow-up). Study III) Patients with early (n=223) and delayed stroke (n=116) were identified among 10809 patients undergoing cardiac and aortic surgery, both groups exposed to cardiopulmonary bypass. Stroke patients were subdivided by the hemispheric location of lesions. Subgroups were compared and their associated pre- and peroperative variables and survival were analyzed. Study IV) Aortic cross-clamp manipulation was studied in a human cadaveric perfusion model. The pressurized aorta was repeatedly cross-clamped and washout samples were collected before and after clamp maneuvers. Particles in the washout samples were evaluated by microscopy and by digital image analysis. Study V) Pig aortas were pressurized and cannulated. Washout samples were collected before and after cannulation (n = 40). Particles were deposited onto a 10-μm filter to be evaluated by microscopy and digital image analysis. Results: Study I) In the group of patients exposed to routine cardiac surgery (i.e., clamping and cannulation) and with early stroke, right-hemispheric lesions were more frequent than of the contra-lateral side (P=0.005). Patients with aortic dissections had a strong dominance of bilateral findings, which was different from the unilateral pattern in the routine-surgery group (P<0.001). Study II) Early and delayed stroke did not share any risk factors. Both early and delayed stroke explained mortality in the early postoperative period (P<0.001, P<0.001 respectively) but also at long term follow-up (P=0.008, P<0.001 respectively). For patients surviving their first postoperative year, delayed but not early stroke influenced long-term mortality (P=0.001 and P=0.695, respectively). Study III) Stroke lesions in association to cardiac surgery were near exclusively ischemic. Early stroke had a preponderance for right-hemispheric lesions (P=0.009). In contrast, patients with early stroke that had undergone surgery of the aorta with circulatory arrest showed a pattern with more bilateral lesions compared to ‘cardiac-type’ operations (P<0.001). Patients with bilateral lesions had a dramatically impaired survival compared to those with unilateral lesions (P<0.001). Study IV) In the cadaveric perfusion model, cross-clamping produced a significant output of particles, which was seen for size intervals of 1 mm and smaller (P=0.002 to P=0.022). In all size intervals the particle output correlated with the degree of overall aortic calcification (P =0.002 to P=0.025). Study V) At cannulation of the pig aorta, more particles were noted after cannulation compared to before the maneuver (P<0.001). This increase included small (<0.1 mm, P<0.001) and intermediate-size particles (0.1-0.5 mm, P< 0.001). Particles above 0.5 mm were few and were not associated with cannulation. Conclusions: The influence of stroke on mortality was devastating, for both early and delayed stroke. These two stroke groups had obvious differences in both their risk factors and their hemispheric distribution. It is here emphasized that early and delayed stroke should be considered as two separate entities with suggested mechanistic differences. Ischemic lesions accounted for near all stroke events seen in association to cardiac surgery. For early stroke, these were mostly located within the right hemisphere. Results from the experimental studies underscore microembolic risks associated with aortic manipulation.

This thesis describes the management of patients treated with mechanical circulatory support devices for short- or long-term use. Twenty-four patients suffering from postcardiotomy heart failure were treated with a minimally invasive axial flow pump. The device was effective in unloading the failing left ventricle and in maintaining an adequate systemic circulation. The principles of perioperative monitoring, and pharmacological therapy are outlined. The pump was also used as an alternative to the heart-lung machine in conjunction with coronary artery bypass surgery. Together with a short-acting β-blocker, esmolol, the heart was decompressed and heart motion was reduced, facilitating bypass surgery on the beating heart. The anesthesiological considerations using this method are described. An implantable left ventricular assist device was used as a bridge to heart transplantation in 10 patients. We were interested in assessing the possibility to establish such a treatment program at a non-transplanting center. A multidisciplinary approach was enabled thanks to the organization of our Heart Center and due the close collaboration with our transplant center at Lund University. As one of the first centers in Europe, we established a well-functioning program with good results. Nine out of 10 of the bridge patients, with treatment times varying between 53 to 873 days, survived pump treatment and were eventually transplanted. The device proved to be powerful enough to support the failing heart and enable rehabilitation of the patients. Outpatient management became simpler when using the electrical device with belt-worn batteries. The uncertain durability and the high risk of device-related complications are shortcomings that limit its potential for more permanent treatment of heart failure. A new generation of small implantable axial blood flow pumps has therefore been developed. The principles of these pumps are based on the first generation axial flow pumps evaluated in this thesis. After several years of basic research and experimental studies, the first human implants have been performed. In the thesis, the hemodynamic effects of such a novel axial flow pump have been evaluated in an acute heart failure model. This technology holds great promise, both as a bridge to heart transplantation, and as a permanent circulatory support system. / On the day of the public defence the status of the article IV was: Submitted for publication.

In cardiac surgery, sternal wound infection (SWI) continues to be one of the most serious postoperative complications. Coagulase-negative staphylococci (CoNS) have become the most common causative agents of SWI. Prophylaxis with intravenous beta-lactam antibiotics (cephalosporins or in Sweden most commonly isoxazolyl penicillins) is routinely practised. However, many CoNS species are resistant to beta-lactam antibiotics. Vancomycin is often the only effective antibiotic available for treatment of these infections, but its use for routine prophylaxis is strongly discouraged because of the risk of increasing the selection of resistant bacteria. The aim of this work was to develop and evaluate a new technique for antibiotic prophylaxis in cardiac surgery consisting of application of drug eluting collagen-gentamicin sponges in the sternal wound in addition to conventional intravenous antibiotics. The antibiotic concentrations in the wound and serum achieved by routine intravenous dicloxacillin prophylaxis and those after application of local collagen-gentamicin in the sternal wound were investigated. These studies showed dicloxacillin levels adequate for prevention of infections by methicillin-susceptible staphylococci, and extremely high gentamicin levels in the wound fluid, during the first 8-12 hours postoperatively with the local application. Two thousand cardiac surgery patients were then randomised to routine prophylaxis with intravenous isoxazolyl penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. The primary end-point was any sternal wound infection within two months postoperatively. Evaluation was possible in 983 and 967 patients in the treatment and control groups, respectively. The incidence of any sternal wound infection was 4.3% in the treatment group and 9.0 % in the control group (relative risk = 0.47, (95% confidence interval 0.33 to 0.68); P<0.001). The most common microbiological agents were CoNS, followed by Staphylococcus aureus. Local gentamicin reduced the incidence of SWIs caused by all major, clinically important microbiological agents except Propionibacterium acnes. Assignment to the control group, high body mass index, diabetes mellitus, younger age, single or double internal mammary artery, left ventricular ejection fraction less than 35% and longer operation time were independent risk factors for SWI in a multivariable risk factor analysis. In patients with additional sternal fixation wires (> six wires) the collagen-gentamicin prophylaxis was associated with an approximately 70 % reduction in the incidence of SWI at all depths and the application of collagen sponges between sternal halves may require particular attention regarding the stability of fixation. A cost effectiveness analysis showed that the application of local collagen-gentamicin as prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections. Routine use of the described prophylaxis in all adult cardiac surgery patients could be recommended.