1. |
- Johnsson, Per, et al.
(author)
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Increased S100B in blood after cardiac surgery is a powerful predictor of late mortality
- 2003
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In: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 75:1, s. 162-168
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Journal article (peer-reviewed)abstract
- BackgroundLong-term outcome in patients who suffered stroke after undergoing a cardiac operation has been investigated sparingly, but increased long-term mortality has been reported. S100B is a biochemical marker of brain cell ischemia and blood–brain barrier dysfunction. The aim of this investigation was to record the long-term mortality in consecutive patients undergoing cardiac operations and to explore whether increased concentrations of S100B in blood had a predictive value for mortality.MethodsProspectively collected clinical variables, including S100B, in 767 patients who survived more than 30 days after a cardiac operation, were analyzed with actuarial survival analysis and 678 patients were analyzed with Cox multiple regression analysis.ResultsForty-nine patients (6.4%) were dead at follow-up (range, 18 to 42 months); 11.5% (88 of 767 patients) had elevated S100B 2 days after operation (range, 38 to 42 hours). The probability for death at follow-up was 0.239 if the S100B level was more than 0.3 μg/L, and 0.041 if it was less than 0.3 μg/L. The clinical variables independently associated with mortality were preoperative renal failure, preoperative low left ventricular ejection fraction, emergency operation, severe postoperative central nervous system complication, and elevated S100B values, which turned out to be the most powerful predictor.ConclusionsEven slightly elevated S100B values in blood 2 days after cardiac operation imply a bad prognosis for outcome, and especially so in combination with any central nervous system complication.
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2. |
- Jönsson, Henrik, et al.
(author)
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Controversial significance of early S100B levels after cardiac surgery
- 2004
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In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 4:1
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Journal article (peer-reviewed)abstract
- BackgroundThe brain-derived protein S100B has been shown to be a useful marker of brain injury of different etiologies. Cognitive dysfunction after cardiac surgery using cardiopulmonary bypass has been reported to occur in up to 70% of patients. In this study we tried to evaluate S100B as a marker for cognitive dysfunction after coronary bypass surgery with cardiopulmonary bypass in a model where the inflow of S100B from shed mediastinal blood was corrected for.Methods56 patients scheduled for coronary artery bypass grafting underwent prospective neuropsychological testing. The test scores were standardized and an impairment index was constructed. S100B was sampled at the end of surgery, hourly for the first 6 hours, and then 8, 10, 15, 24 and 48 hours after surgery. None of the patients received autotransfusion.ResultsIn simple linear analysis, no significant relation was found between S100B levels and neuropsychological outcome. In a backwards stepwise regression analysis the three variables, S100B levels at the end of cardiopulmonary bypass, S100B levels 1 hour later and the age of the patients were found to explain part of the neuropsychological deterioration (r = 0.49, p < 0.005).ConclusionsIn this study we found that S100B levels 1 hour after surgery seem to be the most informative. Our attempt to control the increased levels of S100B caused by contamination from the surgical field did not yield different results. We conclude that the clinical value of S100B as a predictive measurement of postoperative cognitive dysfunction after cardiac surgery is limited.
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4. |
- Ederoth, Per, et al.
(author)
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Blood-brain barrier transport of morphine in patients with severe brain trauma
- 2004
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 57:4, s. 427-435
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Journal article (peer-reviewed)abstract
- AIMS: In experimental studies, morphine pharmacokinetics is different in the brain compared with other tissues due to the properties of the blood-brain barrier, including action of efflux pumps. It was hypothesized in this clinical study that active efflux of morphine occurs also in human brain, and that brain injury would alter cerebral morphine pharmacokinetics. METHODS: Patients with traumatic brain injury, equipped with one to three microdialysis catheters in the brain and one in abdominal subcutaneous fat for metabolic monitoring, were studied. The cerebral catheter locations were classified as 'better' and 'worse' brain tissue, referring to the degree of injury. Morphine (10 mg) was infused intravenously over a 10-min period in seven patients in the intensive care setting. Tissue and plasma morphine concentrations were obtained during the subsequent 3-h period with microdialysis and regular blood sampling. RESULTS: The area under the concentration-time curve (AUC) ratio of unbound morphine in brain tissue to plasma was 0.64 (95% confidence interval 0.40, 0.87) in 'better' brain tissue (P < 0.05 vs. the subcutaneous fat/plasma ratio), 0.78 (0.49, 1.07) in 'worse' brain tissue and 1.00 (0.86, 1.13) in subcutaneous fat. The terminal half-life and T(max) were longer in the brain vs. plasma and fat, respectively. The relative recovery for morphine was higher in 'better' than in 'worse' brain tissue. The T(max) value tended to be shorter in 'worse' brain tissue. CONCLUSIONS: The unbound AUC ratio below unity in the 'better' human brain tissue demonstrates an active efflux of morphine across the blood-brain barrier. The 'worse' brain tissue shows a decrease in relative recovery for morphine and in some cases also an increase in permeability for morphine over the blood-brain barrier.
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5. |
- Samuelsson Palmgren, Gabriella, et al.
(author)
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Platelet retention in coronary artery bypass surgery with and without a heart-lung machine. Cause of thrombosis in coronary artery bypass surgery
- 2000
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In: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 34:3, s. 301-306
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Journal article (peer-reviewed)abstract
- The aim of this study was to examine platelet function after coronary artery bypass grafting (CABG) with and without the use of extracorporeal circulation (ECC). Sixteen male patients scheduled for CABG with (n = 8) and without (n = 8) ECC were included in the study. Platelet retention, as measured with a glass-bead retention test, was examined daily during the first postoperative week. Von Willebrand factor (vWF), ristocetin co-factor (Rcof) and prothrombin fragment (PF 1 + 2) were analyzed the day after the operation. We found a significant increase (p < 0.0001) in platelet retention during the first postoperative week after CABG. There was a tendency (not statistically significant) towards a more pronounced increase in the group operated on without ECC. This increase occurred despite the fact that all patients were treated with aspirin (75 mg daily) from the first postoperative day. The median time to maximal postoperative platelet retention was 2 days. In 3 patients platelet retention increased to more than 6 times the basal level.
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6. |
- Steen, Stig, et al.
(author)
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Transplantation of lungs from a non-heart-beating donor
- 2001
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In: The Lancet. - 1474-547X. ; 357:9259, s. 825-829
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Journal article (peer-reviewed)abstract
- BACKGROUND: In animals, we have previously done successful lung transplantations using organs from non-heart-beating donors. We have also developed an ex-vivo system of assessing the function of such organs before transplantation. The next stage was to try the technique in human beings. Bearing in mind the sensitive ethical issues involved, our first aim was to find out what procedures would be acceptable, and to use the results to guide a clinical lung transplantation from a non-heart-beating donor. METHODS: The ethical acceptability of the study was gauged from the results of a broad information programme directed at the general public in Sweden, and from discussions with professionals including doctors, nurses, hospital chaplains, and judges. The donor was a patient dying of acute myocardial infarction in a cardiac intensive-care unit after failed cardiopulmonary resuscitation. The next of kin gave permission to cool the lungs within the intact body, and intrapleural cooling was started 65 min after death. Blood samples were sent for virological testing and cross matching. The next of kin then had time to be alone with the deceased. After 3 h, the body was transported to the operating theatre and the heart-lung block removed. The lungs were assessed ex vivo, and the body was transported to the pathology department for necropsy. RESULTS: No contraindications to transplantation were found, and the right lung was transplanted successfully into a 54-year-old woman with chronic obstructive pulmonary disease. The donor lung showed excellent function only 5 min after reperfusion and ventilation, and during the first 5 months of follow-up, the function of the transplanted lung has been good. INTERPRETATION: About half the deaths in Sweden are caused by cardiac and cerebrovascular disease. This group could be a potential source of lung donors. When all hospitals and ambulance personnel in Sweden have received training in non-heart-beating lung donation, we hope that there will be enough donor lungs of good quality for all patients needing a lung transplant.
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7. |
- Sundgren, Pia, et al.
(author)
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Value of conventional, and diffusion- and perfusion weighted MRI in the management of patients with unclear cerebral pathology, admitted to the intensive care unit
- 2002
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In: Neuroradiology. - : Springer Science and Business Media LLC. - 1432-1920 .- 0028-3940. ; 44:8, s. 674-680
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Journal article (peer-reviewed)abstract
- The aim of our retrospective study was to determine the extent to which diffusion- and perfusion- weighted MRI combined with conventional MRI could be helpful in the evaluation of intensive care unit (ICU) patients who have unknown or unclear cerebral pathology underlying a serious clinical condition. Twenty-one ICU patients with disparity between the findings on brain CT scan and their clinical status were studied. All patients underwent conventional MR and diffusion-weighted imaging and 14 also had MR perfusion studies. Abnormalities were present on diffusion-weighted imaging of 17 of the 21 patients and on perfusion-weighted studies of 7 of 14 patients. The MRI results changed the preliminary/working diagnosis in six patients. In eight other patients, MRI revealed additional pathology that had not been suspected clinically, and/or characterized more closely findings that had already been detected by CT or suspected clinically. MRI showed abnormalities in four of the five patients who had normal CT. MRI findings suggested a negative clinical outcome in all nine patients who subsequently died. MRI findings also suggested positive long-term outcome in five of nine patients who improved significantly as based on Glasgow and extended Glasgow outcome scales. In the three unconscious patients who had normal diffusion- and perfusion weighted imaging the clinical outcome was good. This study suggests that MRI in seriously ill ICU patients with unclear cerebral pathology can provide information that changes, characterizes, or supports diagnoses and/or prognoses and therefore facilitates further management.
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10. |
- Göthberg, Sylvia, 1953
(author)
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New modes of improving ventilation and oxygenation in pulmonary hypertension and acute respiratory failure in newborns and children
- 2000
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Doctoral thesis (other academic/artistic)abstract
- Pulmonary hypertension leading to hypoxemia is a potentially life-threatening condition in pediatric intensive care. Hypoxemia may also result from conditions not primarily related to pulmonary hypertension. The pediatric patients with these symptoms are:· Children after surgery on cardiopulmonary bypass with pulmonary hypertension attributable to congenital heart defects with high pulmonary blood flow.· Newborns with persistent pulmonary hypertension as a symptom of fetal illness or malformation or after a relapse into fetal circulation without obvious reason.· Children with acute respiratory failure and disturbed vascular/alveolar relation with atelectases and ventilation/perfusion mismatch with major pulmonary shunt.New methods to provide better ventilation and oxygenation have been developed over the last few years. The aims of the present thesis were to assess:· The effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on pulmonary hypertension and oxygenation in dose-response studies.· The effect of high frequency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) on alveolar recruitment and response to iNO.· Respiratory inductive plethysmography during dynamic ventilatory changes on high frequency oscillatory ventilation and on conventional ventilation (CV) as a new continuous and non-invasive method to optimize alveolar recruitment without interrupting ventilation.· Possible residual cardiopulmonary and neurological symptoms in a follow-up study after treatment with inhaled nitric oxide.The methods used were dose-response studies with iNO, lung volume recruitment with surfactant, high frequency oscillatory ventilation and partial liquid ventilation, lung volume measurements with respiratory inductive plethysmography and a four-center follow up study after iNO.Results and conclusions:· iNO decreased pulmonary artery pressure after cardiopulmonary bypass. No dose response relationship was found in the dose range of 3-80 ppm nitric oxide. Only a low dose of inhaled nitric oxide was needed, 5 ppm or less, which also concomitantly improved oxygenation in postoperative pulmonary hypertension in children.· iNO in doses up to 20 ppm immediately improved oxygenation in 68% of children with acute respiratory failure. Only 29% of non-responders survived and no delayed response was found in patients with acute respiratory failure. Non-responders need careful attention in order to improve ventilation and/or hemodynamics. Otherwise they should be transferred without delay to extracorporeal membrane oxygenation when eligible for such treatment.· Follow up after iNO treatment showed residual pulmonary hypertension in cardiac but not in lung patients. Residual respiratory disease and neurodevelopmental delay were not increased as compared with previous studies or owing to improved survival of severely ill patients.· In severe respiratory distress syndrome in preterm lambs, rescue treatment with alveolar recruitment strategies, HFOV and PLV, resulted in improved oxygenation. Alveolar recruitment was improved, as indicated by further improvement in oxygenation in response to iNO, particularly when HFOV and PLV were combined. Mean airway pressures on HFOV and CV when combined with PLV were significantly lower, reducing the risk of alveolar barotrauma.· Respiratory inductive plethysmography could be used to assess changes in lung volume during HFOV and CV in term and preterm lambs. This method provided the means to monitor and optimize lung volume continuously, non-invasively and without interruption of ventilation during mechanical ventilation. Observed changes in lung volume predicted changes in oxygenation.
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11. |
- Huss, Fredrik, 1971-, et al.
(author)
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Buses as fire hazards : A Swedish problem only? Suggestions for fire-prevention measures
- 2004
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In: Journal of Burn Care and Rehabilitation. - 0273-8481 .- 1534-5939. ; 25:4, s. 377-380
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Journal article (peer-reviewed)abstract
- In Sweden, approximately 6% of all human transportation is made via buses. The Swedish Board of Accident Investigation and the Swedish Rescue Services Agency have pointed out repeatedly that buses are potential fire and burn hazards, not only when involved in collisions but also in other circumstances. The number of fire incidents is increasing, especially in newer buses. In conjunction with the Swedish Rescue Services Agency, we examined some of the recent bus fires in Sweden. We did not find any casualties, but the results of our study suggest that casualties as a result of bus fires are imminent unless preventive measures are taken. We also studied experiences from previous bus fires and suggest preventive measures.
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16. |
- Johansson, Mats, et al.
(author)
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Changes in intervention and outcome in elderly patients with subarachnoid hemorrhage.
- 2001
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In: Stroke. - 0039-2499 .- 1524-4628. ; 32:12
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: The elderly constitute a significant and increasing proportion of the population. The aim of this investigation was to study time trends in clinical management and outcome in elderly patients with subarachnoid hemorrhage.METHODS: Two hundred eighty-one patients >/=65 years of age with aneurysmal subarachnoid hemorrhage who were accepted for treatment at the Uppsala University Hospital neurosurgery clinic during 1981 to 1998 were included. Hunt and Hess grades on admission, specific management components, and clinical outcomes were recorded. Three periods were compared: A, 1981 to 1986 (before neurointensive care); B, 1987 to 1992; and C, 1993 to 1998.RESULTS: The volume of elderly patients (>/=65 years of age) increased with time, especially patients >/=70 years of age. Furthermore the proportion of patients with more severe clinical conditions increased. A greater proportion of patients had a favorable outcome (A, 45%; B, 61%; C, 58%) despite older ages and more severe neurological and clinical conditions. In period C, Hunt and Hess I to II patients had a favorable outcome in 85% of cases compared with 64% in period A. This was achieved without any increase in the number of severely disabled patients.CONCLUSIONS: Elderly patients with subarachnoid hemorrhage can be treated successfully, and results are still improving. The introduction of neurointensive care may have contributed to the improved outcome without increasing the proportion of severely disabled patients. A defeatist attitude toward elderly patients with this otherwise devastating disease is not justified.
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17. |
- Lourido, J, et al.
(author)
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Correlation between blood glucose concentration and glucose concentration in subcutaneous adipose tissue evaluated with microdialysis during intensive care
- 2002
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In: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 62:4, s. 285-292
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Journal article (peer-reviewed)abstract
- Background: Hyper- as well as hypoglycemia may be detrimental for brain energy metabolism and even a moderate increase in blood glucose concentration can affect outcome adversely. During physiological conditions, glucose concentration obtained from microdialysis of subcutaneous adipose tissue adequately reflects plasma glucose concentration. This study examines whether this correlation is also obtained during intensive care in patients with severe injuries. Methods.. The study included 62 patients with severe traumatic brain injuries. All patients received one 30 mm microdialysis catheter (CMA 60, CMA Microdialysis) inserted into periumbilical subcutaneous adipose tissue. The probe was perfused (0.3 mul/min) with a Ringer solution from a microinfusion Pump and analyzed for glucose, lactate, and glycerol. The Study included 2.434 simultaneous analyses of glucose concentration in arterial blood and subcutaneous adipose tissue. Results.' The correlation coefficient for glucose concentration in blood and interstitial fluid was 0.743 for the whole material. The cot-relation was relatively poor for 1-6h after insertion of the probes, During this period. a continuous increase in the Subcutaneous level Of glucose and decreases in lactate and glycerol were noted. Conclusions: The correlation between blood glucose concentration and glucose Concentration in subcutaneous adipose tissue was not as good during intensive care as in normal humans. The poor correlation during the first 6h probably reflects a stress reaction (and possibly local vasoconstriction). Microdialysis of subcutaneous adipose tissue permits frequent bedside analyses of the biochemical composition of the extracellular fluid and may be of value during routine intensive care provided the methodological limitations are recognized.
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20. |
- Boström, Barbro
(author)
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Acute postoperative and cancer-related pain management, Patients´ experiences and perceptions in relation to health-related quality of life and the multidimensionality of pain
- 2003
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Doctoral thesis (other academic/artistic)abstract
- This thesis describes patients in acute postoperative pain as well as patients with acute cancer-related pain in palliative care, and their experiences and perceptions of pain management in relation to HRQOL and the multidimensionality of pain. A combination of qualitative and quantitative methods was chosen. Data were collected using interviews and questionnaires; APS, SF:36 and a new developed questionnaire PC-PPQ measuring care related to pain management in palliative care. For assessing pain VAS and Pain-o-Meter were used. The study group consisted of 100 patients on their second postoperative day, and of 75 patients with cancer-related pain from two palliative care teams. The result showed that at the time of the interview 29 of the patients with postoperative pain reported a pain > 3 on VAS and 79 reported VAS > 3 as worst pain past 24 hours. The higher the intensity of pain the less satisfied the postoperative patients were with the nurses´ way of treating their pain. Thirty-three patients stated that they had received information regarding the importance of pain relief. Patients with postoperative pain as well as patients with cancer-related pain had been prescribed analgesics mostly a combination of Paracetamol, NSAID and opioid. Of the 75 patients with cancer-related pain and in palliative care 22 patients reported pain >3 on POM-VAS and 47 patients reported >3 on POM-VAS as worst pain past 24 hours. Twenty-eight patients reported an average pain > 3 on POM-VAS past 24 hours. Twenty-four patients used the words troublesome or tiring when describing their affective pain. Sensory pain was described as prickling or sore by 15 patients. The patients perceived their pain as “aching all over” and expressed a wish for pain relief as well as a fear for increased pain. HRQOL especially physical functioning decreased for patients with average pain > 3. Being cared for by a nurse-led or a physician-led palliative care team indicated no statistically significant differences for patients´ HRQOL or pain intensities. The patients had experienced a statistically significant better care after being referred to a palliative care team, despite that pain control had not been optimized. Patients expressed a need for communication, planning and trust in order to improve pain management. Continuity of care and the opportunity to talk increase the patients feeling of security, as well as improved their perceived pain control. Structured ongoing discussion concerning pain management from an early stage of the disease or already preoperatively can provide an important intervention to meet the results of this thesis. Pain assessment covering the multidimensionality of pain, and pain treatment plans including both pharmacological and non-pharmacological treatment are further important interventions.
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21. |
- Nilsson, Ulrica, 1960-, et al.
(author)
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Improved recovery after music and therapeutic suggestions during general anaesthesia : a double-blind randomised controlled trial
- 2001
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 45:7, s. 812-817
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Journal article (peer-reviewed)abstract
- Purpose: This study was designed to determine whether music or music in combination with therapeutic suggestions in the intra-operative period under general anaesthesia could improve the recovery of hysterectomy patients.Methods: In a double-blind randomised clinical investigation, 90 patients who underwent hysterectomy under general anaesthesia were intra-operatively exposed to music, music in combination with therapeutic suggestion or operation room sounds. The anaesthesia was standardised. Postoperative analgesia was provided by a patient-controlled analgesia (PCA). The pain scores were recorded by means of a visual analogue scale. Nausea, emesis, bowel function, fatigue, well-being and duration of hospital stay were studied as outcome variables.Results: On the day of surgery, patients exposed to music in combination with therapeutic suggestions required less rescue analgesic compared with the controls. Patients in the music group experienced more effective analgesia the first day after surgery and could be mobilised earlier after the operation. At discharge from the hospital patients in the music and music combined with therapeutic suggestion group were less fatigued compared to the controls. No differences were noted in nausea, emesis, bowel function, well-being or length of hospital stay between the groups.Conclusion: This double-blind study has demonstrated that intra-operative music and music in combination with therapeutic suggestions may have some beneficial effects on postoperative recovery after hysterectomy. Further controlled studies are necessary to confirm our results.
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22. |
- Chen, Luni, 1962-
(author)
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Inhaled Nitric Oxide Therapy : Non-response and Rebound Response
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Therapeutic inhaled nitric oxide (INO) has proved beneficial in patients with pulmonary hypertension. However, around 30-40% of the patients are non-responders to this therapy, and a life-threatening rebound response may occur during attempts to withdraw INO. This thesis investigated the link between vasoconstrictors and non- and rebound responses in piglets subjected to acute lung injury by exposure to endotoxin or oleic acid (OA). We found that INO had strong effect in mainly ET-1 related, endotoxin-induced pulmonary hypertension, and there was a rebound response after INO withdrawal. Thus, the weaker the response to INO, the greater the rebound. Neither response nor rebound was seen in oleic acid-induced, mainly prostaglandin related pulmonary hypertension. INO decreased expression of the ET-A receptor, and this might be another signal transduction pathway whereby INO relieves pulmonary vasoconstriction besides increasing c-GMP. Thus INO might have better effect in pulmonary vasoconstriction that is mainly mediated by ET-1 than when other vasoconstrictors are involved in the vascular reaction. Increased production and/or release of vasoconstrictor peptide endothelin-1 (ET-1) during INO, and release of prostaglandin TXA2 and PGF2α after INO withdrawal, were more important causes of the rebound, than a decreasing endogenous NO production during INO. The latter mechanism has been proposed in previous studies. An increase in prostaglandins after INO withdrawal is possibly secondary to the increase in ET-1 during INO. Combination of INO with the COX inhibitor diclofenac blocked the rebound reaction. These findings may open the way for new therapeutic modalities.
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24. |
- Jensen, Eva
(author)
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Protein S-100, inflammatory and haemostatic mediators in paediatric open heart surgery. Influence of clinical variables and a biocompatible cardiopulmonary bypass system
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Cardiopulmonary bypass (CPB) is used in most operations when correcting congenital heart malformations. Postoperative neurological problems (temporary or permanent) are complications of the procedure. These neurological injuries, especially if they are minor, are difficult to recognise in small children. CPB gives rise to activation of the inflammatory response. This response can, in extreme cases, result in hypotension, fever, coagulopathies, oedema, tissue injury and organ failure. Protein S-100 , a possible biochemical marker for neurological injury measurable in blood, was studied in paediatric general surgery patients and patients operated on for congenital heart malformations. Markers indicating activation of the inflammatory response: complement factors, pro-inflammatory cytokines, PMN elastase and factors from the coagulation and fibrinolytic systems were described. Relations between measured variables and clinical variables were tested. The possibility of influencing the response in activation of inflammation and haemostasis when using a biocompatible perfusion system compared with a conventional system was investigated. All children who participated in the studies were below three years of age. Young children unlike adults have age dependent (inverted correlation) measurable concentrations of S-100 in blood before operation. Both heart surgery and general surgery increase S-100 during surgery which cast doubt on the neuro-specificity of the marker in connection with surgery. Open heart surgery with CPB leads to activation of the complement system and the release of PMN elastase and pro-inflammatory cytokines. Pre-and peroperative clinical variables are related to the inflammatory response, which is related to the postoperative course. The use of a biocompatible perfusion system as compared with a conventional perfusion system reduces complement activation and measurable levels of PMN elastse, but does not influence activation of pro-inflammatory cytokines. It also leads to less activation of fibrinolysis during CPB.
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25. |
- Ederoth, Per
(author)
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Microdialysis and Intensive Care. Clinical and experimental studies.
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Microdialysis was used to monitor local concentrations of energy metabolites in different organs, and to study the pharmacokinetics of morphine over the blood-brain barrier in intact and injured brain tissue in conditions treated in the Intensive Care Unit. After major abdominal or thoracoabdominal surgery, postoperative thoracic epidural analgesia resulted in higher glycerol concentrations in the deltoid subcutaneous adipose tissue, implying increased lipolysis, on the third postoperative day as compared to intravenous infusion of morphine, possibly due to a locally increased sympathetic tone. In patients with severe traumatic brain lesions, the correlation between the glucose concentrations in blood and abdominal subcutaneous adipose tissue was poor during the first 6 hours of intensive care, with lower levels in the tissue than in blood. Experimental pancreatitis in the rat immediately increased the interstitial concentrations of glucose and lactate in the pancreas. In the small intestine, a remote organ, a significant increase of lactate and the lactate/pyruvate ratio started already one hour after induction of pancreatitis. Experimental meningitis in the piglet increases the exposure of the brain to unbound morphine. The terminal half-life for unbound morphine in the brain was similar during meningitis and the control period. Significant decreases in relative recovery for nalorphine during meningitis and for morphine in traumatized brain tissue in humans as compared to relatively intact brain tissue was demonstrated. In the human brain, pharmacokinetic evidence of active efflux of unbound morphine over the blood-brain barrier was found. The terminal half-life for unbound morphine was longer than in plasma and unaffected by brain tissue trauma. The time to maximum concentration for unbound morphine was longer in the uninjured brain tissue as compared to the subcutaneous adipose tissue. In some patients there was an increased morphine exposure in the extracellular fluid in the human brain. This was not seen in uninjured brain tissue in patients with surgically evacuated focal mass lesions.
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26. |
- Ekman, Andreas, et al.
(author)
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Reduction in the incidence of awareness using BIS monitoring
- 2004
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In: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 48, s. 20-26
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Journal article (peer-reviewed)abstract
- Reduction in the incidence of awareness using BISmonitoringA. EKMAN1,M-L.LINDHOLM1,C.LENNMARKEN2and R. SANDIN11Department of Anaesthesia and Intensive Care, Regional hospital, Kalmar, and The Karolinska Institute, Stockholm, and2Department ofAnaesthesia and Intensive Care, University Hospital, Linko¨ping, SwedenBackground: Explicit recall (ER) is evident i n a pproximat ely0.2% of patients given general anaesthesia including musclerelaxants. This prospective study was performed to evaluate ifcerebral monitoring using BIS to guide the conduction ofanaesthesia could reduce this incidence significantly.Patients and methods: A prospective cohort of 4945 consecutivesurgical patients requiring muscle relaxants and/or intubationwere monitored with BIS and subsequently interviewed for ERon three occasions. BIS values between 40 and 60 were recom-mended. The results from the BIS-monitored group of patientswas compared with a historical group of 7826 similar cases in aprevious study when no cerebral monitoring was used.Results: Two patients in th e BIS-monitored grou p, 0 .0 4% ,hadER as c ompared with 0.18% in the control group (P < 0.038).Both BIS-monitored patients with ER were aware during intub-ation when they had high BIS values (>60) for 4 min andmore than 10 min, respectively. However, periods with high BIS ¼ 4 min were al so eviden t in other patient s with no ER .Episodes with high BIS, 4 min or more, were found in 19% ofthe monitored patients during induction, and in 8% of casesduring maintenance.Conclusions: The use of BIS monitoring during general anaes-thesia requiring endotracheal intubation and/or muscle relax-ants was associated with a significantly reduced incidence ofawareness as compared with a historical control population.
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27. |
- Ersson, Anders
(author)
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Infammatory response to hyperbaric trauma. An experimental and clinical study
- 2003
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Doctoral thesis (other academic/artistic)abstract
- Reductions in ambient pressure liberates gas in various tissues and can result in decompression illness. In this thesis the patophysiological implications of a blood gas interface resulting from decompression was investigated with reference to the influence on biochemical mediators of inflammation. In a series of experiments, animals and human subjects have been exposed to hyperbaric trauma of different severity and duration. The hyperbaric exposures were performed using a dry decompression chamber and in open water dives. Post dive bubbledetection in the venous circulation was performed using echocardiography and levels of inflammatory mediators were analysed. The main results and conclusions were : • Dives in accordance with normal diving tables produces intravascular bubbles in the venous circulation, not necessarily correlated to clinical symptoms of DCS. Bubbles can be detected for as long as 16 h post dive. • A verified blood - gas interface after decompression seems capable of activating inflammatory cells and pro-inflammatory mediators as well as to stimulate an anti-inflammatory counter- response in a dose dependent fashion. • The magnitude of the systemic pro inflammatory response seem to correlate to the severity of the hyperbaric trauma in that way that only a trauma severe enough to cause profound clinical DCS resulted in systemic significant levels of proinflammatory mediators. • The response of an acute hyperbaric trauma were found to be different from a repetitive one in respect of the anti-inflammatory response, suggesting an adaptation mechanism of the anti-inflammatory system. • The findings presented in this thesis are consistent with different levels of activation of the inflammatory system. It is plausible that the bubble formation during decompression is the trigger of this inflammatory response. It is therefore suggested that the interplay between pro- and anti-inflammatory substances is a fine-tuned balance-act and it is only when this balance collapses that morbidity ensues. • The inflammatory interplay demonstrated in this thesis suggests an inflammatory mechanism as part of the pathogenesis in DCS.
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28. |
- Flisberg, Per
(author)
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Aspects of Postoperative Pain Relief with Special Emphasis on Epidural Analgesia and Major Non-Cardiac Surgery
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Postoperative pain relief with opioids after major non-cardiac surgery may give rise to adverse effects. The fear of dangerous side effects may therefore limit the optimal use of different treatment modalities in surgical wards. Opioids can be administered alone as an intravenous infusion, or in combination with local anaesthetics as an epidural infusion. Both regimes can be tailored with a patient-controlled option. In the present thesis we evaluated postoperative efficacy and adverse effects of morphine and local anaesthetics administered for postoperative pain relief either as intravenous pain relief (morphine), or as thoracic epidural analgesia (local anaesthetic/morphine) in conjunction with major non-cardiac surgery. 1) It was found that preoperative thoracic epidural analgesia did not add any benefits regarding pain relief or improved pulmonary function compared to thoracic epidural analgesia started after completion of surgery. 2) In patients undergoing thoraco-abdominal surgery, the use of postoperative thoracic epidural analgesia improved dynamic pain perception compared to intravenously administered morphine for five postoperative days. No inter-group differences were found regarding postoperative attenuation of pulmonary function. 3) A new monitoring technique revealed that epidural opioids caused respiratory disturbances, i.e. apnea and bradypnea combined with elevated PaCO2 levels in elderly patients during the first postoperative night. This indicates that elderly patients may need closer postoperative respiratory monitoring. 4) Pump administered pain relief in 2,696 patients in surgical wards for several days demonstrate few serious adverse effects. However, continuous intravenous morphine PCA was associated with a higher incidence of respiratory depression, hallucinations, sedation, and nightmares compared to the use of thoracic epidural analgesia. The latter was also found to mitigate pain more effectively, both at rest and during mobilization, compared to intravenous morphine.
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29. |
- Granberg Axèll, Anetth
(author)
-
The Intensive Care Unit syndrome/delirium, patients' perspective and clinical signs
- 2001
-
Doctoral thesis (other academic/artistic)abstract
- When a person becomes critically ill, injured and/or undergoes major surgery and requires intensive care, a complex dilemma can arise. The condition of the illness, the specific caring situation and the environment lead to significant changes and effects in the senses and perceptional abilities. Under these conditions some patients can develop symptoms of the Intensive Care Unit syndrome/delirium. The aim of this thesis was to describe, illuminate and explore the ICU syndrome/delirium from the patients perspective; and to investigate the clinical signs and some demographic and clinical data which could be related to the ICU syndrome/delirium seen in mechanically ventilated patients having had a stay at the ICU of more than 36 hours. Observations and interviews were used as methods in the hermeneutic approaches. A total of 31 patients were observed during their stay at the ICU and of these 19 patients were interviewed twice after discharge. Observations: The patients exhibited a great variety of clinical signs of the ICU syndrome/delirium. The clinical signs were characterised by a fluctuating ability to establish contact or communicate. Even the ability to control or move the body fluctuated; the ability to rest i.e. the patients could fall asleep for a few minutes and then suddenly become anxious, restless, plucking, and mumbling. Some patients could appear very communicative and active, moving about all the time, trying to get out of bed, and being in a good mood, but could suddenly recount odd experiences, become aggressive and unable to focus on any other person, or concentrate, or listen. Most patients were disoriented as to time and place. Interviews: Upon regaining consciousness, patients described a state of chaos. This chaos could result in a loss of control over body, mind and circumstances, and into a condition of persistent inner tension or prolonged fear. The patients remembered their time at the ICU with a "jigsaw puzzle" recall but their "unreal experiences" in detail. "Unreal experiences" are phenomena, which appear in an experienced total wakeful condition or in a condition between wakefulness and sleep, they are experienced as real, and can appear at any time, meaning that anything could cause or trigger them, but tend to appear more frequently, and usually with more severity, at night and when the patient tries to sleep. In the present paper, the 19 patients were classified into different groups of patterns and intensities of "unreal experiences" and i.e. severe delirium (SD) moderate delirium (MD) and mild/non delirium. Patients in the group SD had significantly lower haemoglobin concentrations than those in the other groups. There was a tendency towards a similar but less significant difference in PaO2 between the groups. SD patients had both significantly longer duration of mechanical ventilation, longer stays in the ICU, and significantly higher doses of both fentanyl and midazolam than those having moderate or no symptoms of delirium. The clinical signs do not seem to be separate phenomena, but related and connected to each other, and also to patients' verbal expressions. Therefore clinical signs and verbal expressions must be regarded as a coherent whole. The patient's experiences related in the interviews gave an inside perspective on the ICU world and what it feels like to suffer from the ICU syndrome.
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30. |
- Holbeck, Staffan
(author)
-
Transvascular exchange and organ perfusion with reference to colloid and hypertonic solutions, and to endotoxaemia
- 2001
-
Doctoral thesis (other academic/artistic)abstract
- Changes in vascular permeability can immensely change plasma volume and affect the degree of oedema in the body. In diseases with an increased vascular permeability, adequate fluid therapy is of considerable importance to prevent hypovolaemia. Mechanisms behind differences in effectiveness of various plasma volume expanders to restore a low plasma volume and a compromised microcirculation are still not fully understood. This thesis based on experimental studies on cat, analysis colloid and hypertonic plasma volume expanders regarding their effects on transvascular fluid exchange and vascular permeability in skeletal muscle during and after discontinuation of the infusions. In addition, permeability effects are analysed in skeletal muscle following endotoxin infusion, as well as effects of plasma volume substitution on intestinal perfusion and metabolism in endotoxaemia. The autoperfused right hind limb skeletal muscle was enclosed in a plethysmograph allowing continuous measurements of tissue volume variations. Capillary filtration coefficient measurements showed that fluid permeability is decreased by albumin and dextran, unchanged by hydroxyethyl starch (HES), and increased by gelatin. Measurements of change in the reflection coefficient for albumin showed no direct effect on albumin permeability of dextran, gelatin, or hydroxyethyl starch. Hypertonic saline increased fluid permeability an effect not seen with mannitol and urea. Muscle volume was decreased by 20% albumin, unchanged by 6% dextran 70 and 6% HES 200/0.5, and increased by 3.5% gelatin. Gelatin and HES, but not dextran and albumin induced rebound filtration, indicating interstitial accumulation of the colloid molecules. Hypertonic saline, mannitol and urea induced absorption of which hypertonic saline was most effective and mannitol less effective over time in relation to osmotic capacity. Mannitol and urea but not hypertonic saline showed rebound filtration indicating intracellular accumulation of mannitol and urea. During endotoxaemia, both fluid and albumin permeability increased in skeletal muscle and hypovolaemia was shown to be the major, but probably not the only cause of disturbed intestinal perfusion. No difference could be seen between albumin, dextran, and hydroxyethyl starch in effectiveness to restore intestinal perfusion during endotoxaemia.
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31. |
- Hyllner, Monica, 1964
(author)
-
Preoperative deposit of autologous blood. Effects on inflammatory mediators
- 2003
-
Doctoral thesis (other academic/artistic)abstract
- Blood contains complex cascade systems and substances that can be activated during the processing of blood components and storage. Allogeneic blood, i.e. blood from someone else, is normally separated into components before storage and transfusion, while autologous blood (the patient s own blood) often is used as whole blood. Allogeneic transfusions are associated with a variety of risks and preoperative autologous blood donation (PABD) has therefore become an established alternative. For patients with cancer, the immunosuppressive effect of allogeneic blood may be detrimental, but PABD is difficult because of the urgency of surgery. Normally, PABD begins 4-6 weeks before the scheduled operation and blood is tapped weekly. The additional use of recombinant erythropoietin (rHuEPO) therapy increases the volume of tapped autologous blood before surgery. However, other studies indicate that rHuEPO therapy suppresses postoperative endogenous erythropoietin (EPO) production and stimulates inflammatory mediator release. The aim of the present thesis was to investigate the effects on perioperative erythropoiesis, and the inflammatory mediator release during the predeposit and storage of autologous blood. In the present study, blood from healthy blood donors was collected and stored as whole blood or as separate components. Complement activation and release of pro-inflammatory cytokines were followed during the storage time. In addition, the effect of prestorage leucocyte filtration on inflammatory mediators was studied. Women undergoing radical hysterectomy were scheduled to predeposit three units of autologous blood during two weeks before surgery, with or without rHuEPO therapy. Erythropoiesis and the immune response were investigated during the pre- and postoperative follow-up.The results demonstrate that complement is activated during storage of whole blood and plasma, and the cytokine IL-8 is released during storage of whole blood. Prestorage filtration of plasma activates the complement cascade but does not influence cytokine generation. Clearly, it was possible for women to predeposit three units of blood in only two weeks prior to surgery. A haemoglobin level below the 100 g/l donation limit can be prevented in one patient out of seven, by treating women with rHuEPO. The use of rHuEPO increases the postoperative endogenous EPO response but does not influence the cytokine release. The present thesis suggests that PABD can be offered to female patients undergoing cancer surgery, and that autologous blood can be transfused as whole blood.
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32. |
- Ingimarsson, Jonas
(author)
-
Early ventilatory management and lung function in the immature newly born. Experimental studies in lambs.
- 2003
-
Doctoral thesis (other academic/artistic)abstract
- Using an animal model, the thesis explores how the initial ventilation of the lungs, and surfactant therapy, should best be managed after premature birth. Material and measurements: The studies were made in newborn lambs delivered by cesarean section. Spread of exogenous surfactant was analysed by mixing it with technetium-labelled macroaggregated human serum albumin and imaging the radioactivity with a gamma camera. The effect of surfactant supplementation and different ventilation strategies was analysed with static pressure volume (PV) curves of the respiratory system and by histologic assessment. Main findings: Intratracheally instilled surfactant spread quickly and reached its final place within one minute. If instilled before the first breath, the intrapulmonary distribution of surfactant was uniform. In contrast, giving five large breaths (20 mL/kg) before surfactant resulted in a very uneven distribution, mainly to dependent lung parts. Immature lambs treated in this way also had poorer lung function. However, hyperinflation of the lungs was not always harmful. Notable lung function derangement occurred only if the large breaths were given immediately after birth. Preceding surfactant instillation did not completely protect against the adverse effect of such very early hyperinflations, but already at 10 minutes of age the large breaths were no longer harmful. Also, giving large breaths at 30 min after birth in order to recruit lung volume before delayed surfactant treatment had no positive or negative effect. In lambs given surfactant at birth and not subjected to large breaths, the shape of the P-V curve was investigated. The expiratory, but not the inspiratory, part of the curve was found to be useful for determining optimal positive end-expiratory pressure during mechanical ventilation. Possible clinical implications: In immature newborns, the way ventilation is initiated immediately after birth may determine both the response to surfactant and subsequent lung morbidity.
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33. |
- Johansson, Anders
(author)
-
Modern inhalation agents and effects of anaesthesia equipment during low-flow anaesthesia
- 2003
-
Doctoral thesis (other academic/artistic)abstract
- Volatile agents are economically and ecologically acceptable only when administered via low-flow systems. However, sevoflurane degrades during low-flow anaesthesia to compound A, and a high carbon dioxide absorber temperature increases this degradation. This thesis suggests that there is a correlation between apparatus dead-space volume and absorber temperature during low- and minimal-flow sevoflurane anaesthesia. Increasing the dead-space volume reduces absorber temperature during low- and minimal-flow sevoflurane anaesthesia. The main disadvantage of low-flow techniques is that inspired (In) and end-tidal (Et) anaesthetic agent concentrations are not directly related to the vaporiser setting. In the present studies, with desflurane and sevoflurane, there was a significant difference between Et and In concentrations at fresh gas flows (FGFs) of 1.0 and 2.0 l/min. However, the ratio of Et to In concentration remained fairly constant. Excessive respiratory heat loss may lower body temperature. Artificial humidification of dry inspired gases reduces loss of body heat during anaesthesia, hence the popularity of heat and moisture exchangers (HMEs). In this study, HMEs improved the humidity of the anaesthetic gases at different FGFs, but did not improve maintenance of body temperature during low-flow anaesthesia in adults undergoing elective general or urologic surgery.
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34. |
- Kvorning, Nina
(author)
-
Acupuncture in Obstetrics and Anaesthesia
- 2003
-
Doctoral thesis (other academic/artistic)abstract
- The aims of the present thesis (I-V) were to evaluate the analgesic and adverse effects of manual acupuncture for low-back and pelvic pain during pregnancy (I) and for labour pain (II-III), and also to study the effects of low-frequency electro acupuncture (EA) on clinical physiological responses to skin incision in anaesthetized patients (IV-V). Acupuncture in obstetric patients (I-III) Manual acupuncture in obstetric patients was found to relieve pain in one prospective randomised (I) and two retrospective (II-III) studies. Low-back and pelvic pain intensity during pregnancy was decreased by acupuncture (I), and parturients receiving acupuncture required fewer of the other analgesic modalities than the women in the control group (II-III). Neither patients in the acupuncture group nor their infants suffered from substantial adverse effects (I-III). These findings are in agreement with results obtained by other research groups investigating acupuncture during pregnancy and labour, but future studies are desirable to establish the role of acupuncture in obstetrics. Acupuncture in anaesthetized patients (IV,V) In contrast to the beneficial effects of acupuncture referred above (I-III), two prospective, randomised, placebo-controlled and double-blind studies (IV,V) revealed that low-frequency EA in anaesthetized patients did not attenuate but instead facilitated clinical physiological response to skin incision. Patients given EA required a higher steady state concentration of sevoflurane to abolish physiological reactions to skin incision (IV). Furthermore, when exposed to the same steady state concentration of sevoflurane, more acupuncture than control patients responded to surgery with movements of head or limbs, dilation of pupils or divergence of eye axes (V). Similar results have not been reported elsewhere, although combined high- and low-frequency EA in anaesthetized volunteers was recently reported to have no effect on the response to painful stimulation. In our study, the depth of anaesthesia was not influenced by acupuncture, since the A-line ARX index reflecting AEP activity was found to be similar in the two groups (V). Future studies of the possible mechanisms underlying this effect of EA under general anaesthesia are desirable.
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35. |
- Mellström, Åke
(author)
-
Tissue Perfusion and Oxygenation Evaluated by Measurements of Tissue Gases and pH. An Experiemental Study.
- 2002
-
Doctoral thesis (other academic/artistic)abstract
- Optimum peripheral perfusion, oxygenation and oxygen utilization is a prerequisite for normal wound healing, resistance to infection and cardiac function. The purpose of this study was to evaluate peripheral oxygen utilization by measurements of subcutaneous tissue gases and pH (PscO2, PscCO2 and pHsc) in comparison to established techniques for measurements of periph-eral tissue oxygenation and oxygen utilization in experimental animal models with hyperoxia-hypoxia, acidosis-alkalosis and haemorrhage-resuscitation. The oxygen electrode of polarographic type, Paratrend 7™ was compared with established electrodes of the same type, Biogenesis™ and Continucath 1000™ in an in vitro and an in vivo model. The Paratrend 7 and the Biogenesis sensors generated almost equal tissue oxygen ten-sion values in response to changes in arterial oxygen tension. The Continucath sensor gener-ated 50 % higher tissue oxygen tension values compared with the Paratrend 7 and Biogenesis sensors, both with and without tonometer. During hyperoxia and hypoxia measurements of sub-cutaneous tissue gases and pH are indicators of oxygen utilization. Correction of oxygen utiliza-tion in the subcutaneous tissue as measured by subcutaneous carbon dioxide tension and pH is slower than indicated by changes in subcutaneous oxygen tension, blood gases and pH. Over-compensation of acidosis with bicarbonate resulting in alkalosis impairs oxygenation. Subcuta-neous oxygen tension was an early indicator of changes in peripheral tissue perfusion and oxy-genation during hypovolemia and resuscitation. Measurements of subcutaneous carbon dioxide tension and pH verified inadequate tissue oxygen utilization during shock and recovery from tissue acidosis after resuscitation in contrast to the corresponding measurements in arterial blood. Measurements of subcutaneous tissue gases and pH, to a large extent reflect similar changes in splanchnic perfusion, oxygenation and tissue oxygen utilisation during hemorrhage and resuscitation. Additional measurements of PscCO2 and pHsc in combination with PscO2 generate relevant infor-mation on tissue oxygen utilization in a variety of clinical conditions.
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36. |
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37. |
- Perez de Sá, Valéria
(author)
-
Severe Hemodilution - Clinical and Experimental Studies
- 2002
-
Doctoral thesis (other academic/artistic)abstract
- In children, it is often desirable to minimize allogenic blood transfusion, and this thesis explores the physiology of an alternative method of managing perioperative blood loss: hemodilution with Ringer´s dextran. Methods Clinical studies: Arterial pressure, superior caval venous oxygen saturation (ScvO2) and blood lactate concentration (L) were studied during bone marrow harvesting (BMH) on 23 occasions in 19 children, 1-17 years of age, with healthy hearts and lungs. Experimental studies - A. Shivering was induced by surface cooling and the hemodynamic and metabolic responses studied in hemodiluted (Hgb = circa 50 g/L), 12-14 weeks old anesthetized pigs and their normoemic controls. B. The tolerance to progressive isovolemic anemia was studied during hypothermia in anesthetized and paralyzed pigs (32 °C) and their normothermic controls (38.5 °C). Main findings Clinical studies: BMH caused a blood loss of 26 (17-42) ml per kg body weight, and decreased the blood hemoglobin concentration (Hgb) to 54 (47- 84) g/L. ScvO2 was 72 (61-88) % in the awake child, and increased to 82 (70 - 94) % after induction of general anesthesia. During hemodilution, it decreased to 76 (60-92) %. The lowest ScvO2: 66 (55-79) % was seen after awakening the child in spite of the fact that Hgb had now increased to 70 (58-95) g/L by transfusion of the child´s own, preoperatively collected, blood. There was an increase in mean heart rate from 89 to 108 bpm during BMH. Mean L increased from 1.0 to 1.5 mmol/L but was never above the normal limit. Experimental studies: A. During shivering, oxygen consumption (VO2) increased by a mean factor of 2.9 in the hemodiluted pigs, and 3.7 in the controls (P< 0.001). Two of the former exhibited signs of myocardial hypoxia. B. Hgb at death was 14 ± 4 g/L in cooled pigs and 19 ± 3 g/L in the controls (P=0.015). Clinical implications -The healthy child tolerates extreme hemodilution (Hgb 50-70 g/L) if suitably anesthetized. The strain on the organism is greater after awakening. -The findings cannot be extrapolated to children with compromised function of the heart or lungs, who the author believes will frequently benefit from a normal-high Hgb. -Extreme hemodilution reduces oxygen delivery to the body and will, hence, decrease the tolerance to challenges with increased oxygen demand such as shivering. -Cooling is modestly protective during severe anemia.
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38. |
- Persson, Johan
(author)
-
Physiological and clinical aspects of change in microvascular permeability
- 2004
-
Doctoral thesis (other academic/artistic)abstract
- Microvascular permeability is important for exchange of fluids and proteins in health and in disease. Permeability increases in critical illness, such as during sepsis/SIRS and after trauma, and may be affected by drugs. Increased permeability causes oedema and hypovolaemia. Hypovolaemia is treated with fluids, and their efficacy is determined by their intravascular retention, also influenced by the prevailing permeability. Permeability changes in some of these situations are evaluated in the present thesis.The effects of endogenous NO and prostacyclin on microvascular permeability were analysed, and we found that they reduce fluid and protein permeability, and conclude that dynamic release of NO and prostacyclin may exert bi-directional regulation of permeability.We also found that exercise decreased fluid permeability in skeletal muscle by release of NO, reducing the exercise-induced oedema. Neither NO nor prostacyclin are responsible for exercise hyperaemia.We found that the anti-hypertensive vasopeptidase inhibitor omapatrilat, combining ACE- and NEP-inhibition, increases fluid and protein permeability through increased bradykinin in plasma due to NEP inhibition, a mechanism that may explain the angiooedema sometimes seen with omapatrilat treatment.After haemorrhage on rat with a relatively normal permeability, 5% albumin, 4% gelatin and 6% hydroxyethyl starch (HES) 130/0.4, saline and retransfusion of erythrocytes all had satisfactory plasma volume expanding effects, but albumin was superior the other solutions. After trauma on cat, where permeability was increased, 6% dextran 70 most likely preserved plasma volume better than 5% albumin, which was better than 3.5% gelatin, 6% HES 130/0.4 and saline. These results indicate that the efficacy of colloids as plasma volume expanders is determined by the prevailing microvascular permeability.
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39. |
- Reinsfelt, Björn, et al.
(author)
-
The effects of isoflurane-induced electroencephalographic burst suppression on cerebral blood flow velocity and cerebral oxygen extraction during cardiopulmonary bypass.
- 2003
-
In: Anesthesia and analgesia. - 0003-2999. ; 97:5, s. 1246-50
-
Journal article (peer-reviewed)abstract
- We investigated the effects of isoflurane-induced burst suppression, monitored with electroencephalography (EEG), on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE), and autoregulation in 16 patients undergoing cardiac surgery. The experimental procedure was performed during nonpulsatile cardiopulmonary bypass (CPB) with mild hypothermia (32 degrees C) in fentanyl-anesthestized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular vein bulb oxygen saturation, and jugular venous pressure (JVP) were continuously measured. Autoregulation was tested during changes in mean arterial blood pressure (MAP) within a range of 40-80 mm Hg, induced by sodium nitroprusside and phenylephrine before (control) and during additional isoflurane administration to an EEG burst-suppression level of 6-9/min. Isoflurane induced a 27% decrease in CBFV (P < 0.05) and a 13% decrease in COE (P < 0.05) compared with control. The slope of the positive relationship between CBFV and cerebral perfusion pressure (CPP = MAP - JVP) was steeper with isoflurane (P < 0.05) compared with control, as was the slope of the negative relationship between CPP and COE (P < 0.05). We conclude that burst-suppression doses of isoflurane decrease CBFV and impair autoregulation of cerebral blood flow during mildly hypothermic CPB. Furthermore, during isoflurane administration, blood flow was in excess relative to oxygen demand, indicating a loss of metabolic autoregulation of flow.
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40. |
- Roscher, Roger
(author)
-
Cooling and dopamine
- 2001
-
Doctoral thesis (other academic/artistic)abstract
- There is little knowledge about the circulatory effects of dopamine in hypothermia. Induced hypothermia has been shown to improve outcome in various settings. Hypothermia is also used for preservation of organs that are harvested for transplantation. We evaluated lungs that were topically cooled for 6 hours in non-heart-beating donor pigs by transplanting them into recipient pigs and observing these for 24 hours. Furthermore, we studied the effects of hypothermia and dopamine on myocardial action potentials and contractions in porcine myocardial muscle strips. In addition, the circulatory effects of dopamine were studied in different settings in normo- and hypothermia in anesthetized pigs. We found that lungs that were topically cooled for 6 hours in non-heart-beating donor pigs were suitable for transplantation. Cooling to 32ºC prolonged the porcine myocardial action potential and contraction duration and increased the contractile force. Dopamine prolonged the porcine myocardial action potential and increased contractile force both in normo- and hypothermia. The heart rate was increased by dopamine at both temperature levels. Dopamine either increased (studyI) or did not change the arterial pressure in normothermia, whereas it reduced or caused no change (study V) in arterial pressure in hypothermia. Dopamine increased cardiac output and oxygen delivery in normothermia as well as in hypothermia, apart from in tachcyardic hypothermic piglets, in which dopamine caused aggravation of tachycardia and presumably a too short diastolic filling time. A high dosage of dopamine increased pulmonary vascular resistance at 32ºC. It is concluded that dopamine excerts principally much the same effects at 32ºC as in normothermia. However, dopamine may compromize ventricular filling in hypothermia due to it`s chronotropic effect combined with a hypothermia-induced shortening of diastolic filling time. Dopamine may also decrease the blood pressure substantially in cases where the sympathetic nervous tonus is high, e.g. after surface cooling during light anesthesia. Pulmonary vascular resistance may also be increased by dopamine at high dosages.
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41. |
- Söderberg, Lars, et al.
(author)
-
In-vitro release of bupivacaine from injectable lipid formulations investigated by a single drop technique--relation to duration of action in-vivo.
- 2002
-
In: Journal of Pharmacy and Pharmacology. - 0022-3573. ; 54:6, s. 747-755
-
Journal article (peer-reviewed)abstract
- The aim of this study was to develop an in-vitro release method suitable for injectable slow-release lipid formulations of local anaesthetics (or other drugs). We also aimed that the results of the in-vitro measurements should have a clear relationship to duration of action in-vivo. Six formulations of bupivacaine base in medium-chain triglyceride-glyceryl dilaurate mixtures were developed. A new apparatus was constructed for determination of their in-vitro release profiles. A bulbous glass tube was fixed inside a standard glass bottle, which was then filled with release medium. A stirring magnet was enclosed in the perforated polypropylene cylinder holding the glass tube. The stirring created a continuous, rotating downward flow of medium inside the tube, which kept the lipid phase, introduced by means of a syringe, suspended as a single, free drop. Release profiles were obtained by sampling of the release medium for up to 72 h and analysis by gas-liquid chromatography. The duration of action in-vivo of the respective formulations was tested by the hot-plate method in rats. The release profiles of bupivacaine in-vitro were mono-exponential for four formulations and bi-exponential for the other two. There was a positive correlation between the proportion of glyceryl dilaurate in the formulation and the slow half-life of release of bupivacaine. All formulations showed prolonged duration of action in-vivo, median values within the range 4.5-12 h, as compared with a 2-h effect of bupivacaine hydrochloride solution. A comparison of in-vitro release curves and durations of action in-vivo suggested that to maintain nerve blockade in-vivo the formulations must release bupivacaine at a rate of approximately 350 mug h-1 under the in-vitro conditions. To conclude, we designed and tested a novel apparatus for measuring release of a local anaesthetic (or other drug) from a fluid or semi-solid formulation in-vitro. Release rates obtained in-vitro by means of this technique may be used to guide the development of formulations with suitable durations of action in-vivo. The apparatus is, however, as yet a prototype. Rigorous evaluation of performance should be carried out on devices built to specific standards according to their intended application.
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42. |
- Thorlacius, Karin
(author)
-
Anaesthetics and the blood vessel wall. Actions of propofol and sevoflurane on sympathetic and endothelial control of smooth muscle function.
- 2002
-
Doctoral thesis (other academic/artistic)abstract
- The anaesthetics we use today dose-dependently decrease the mean arterial pressure partly due to direct or indirect effects on the blood vessels. In the present thesis human omental arteries and veins and rat femoral arteries were investigated in vitro concerning the effects of the intravenous anaesthetic propofol and the volatile anaesthetic sevoflurane on the function of the perivascular sympathetic nerves and the endothelial cells. The effects of propofol on the kinetics of the neuronal uptake of noradrenaline were studied in the rat femoral artery. At lower propofol concentrations we found a decrease in the affinity of the noradrenaline transporters, which results in an uptake inhibition. At higher propofol concentrations this inhibition is counteracted by an increase in the efficiency of the uptake. The effects of propofol on endothelium-dependent relaxation (induced by substance P) were studied in human omental arteries and veins. Propofol, at a clinically relevant concentration, was found to promote endothelium-dependent relaxation mediated via hyperpolarization in human omental arteries and via both nitric oxide and hyperpolarization in human omental veins. The effects of sevoflurane on sympathetic neurotransmission were studied in human omental arteries and veins. We found that sevoflurane depresses the sympathetic neuromuscular transmission by lowering the neuronal noradrenaline release and noradrenaline sensitivity in the arteries and by lowering the noradrenaline release in the veins. The effects of sevoflurane on endothelium-dependent relaxation (induced by substance P) were studied in human omental arteries and veins. Sevoflurane was found to promote endothelium-dependent relaxation in human omental arteries and veins probably via an enhancement of the response of smooth muscle cells to relaxing mediators.
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43. |
- Thorsteinsson, Adalbjörn
(author)
-
Lung volumes and lung mechanics in anesthetized children
- 2001
-
Doctoral thesis (other academic/artistic)abstract
- The thesis was intended to fill gaps in the knowledge regarding the normal development of lung volumes and lung mechanics in children, from young infancy to the mid-teens. In particular, data were previously lacking regarding pre-school children. The studies were done during anesthesia and muscle relaxation. Measurements: · Absolute lung volume was obtained with a tracer gas method (sulfur hexafluoride washout). · Relation between airway pressure and lung volume (pressure-volume relation of the respiratory system) was asssessed during a slow intermittently interrupted expiration from 30 to 0 cm H2O of airway pressure. · In a further study, attempts were made to separate P-V relations of the respiratory system into lung and chest wall components. This was done by analyzing esophageal pressure - that was taken to represent pleural pressure - in addition to airway pressure. · In a final study, a tracer gas was again used, now in an attempt to find the point during expiration, where significant airway closure occurred. Main findings: I. Absolute lung volumes, per kg body weight, were less in young infants than in older children. II. The most marked qualitative change (size factor eliminated) in the pressure-volume relation of the respiratory system occurred during infancy. III. In the supine position, esophageal pressure paradoxically remained positive as expiration continued towards low lung volumes and even increased in some instances. When an attempt was made, anyway, to separately assess the various contributions to "total elastance", the chest wall contribution was relatively minor (about 1/10th in infants). IV. The airway "closing phenomenon" occurred at a higher lung volume when the measurement maneuvre included a deep foregoing inspiration (to 30 rather than 20 cm H2O of airway pressure). Interpretation and possible clinical implications of findings: I. The lung is smaller, in relation to weight, in infants than in older subjects. Yet it is known from other studies that the rate of oxygen consumption at rest is greater. This suggests that infants will have reduced tolerance to stresses such as increased oxygen requirement (e.g. due to fever), apnea (e.g. during tracheal intubation), and restriction of lung capacity (e.g. resection of lung parenchyma, pneumonia, hydrothorax). II. The respiratory system of small infants has less elastic recoil than that of older subjects. This probably reflects a low elastin content in the lungs, as described by others. III. In the clinical assessment of mechanically ventilated infants, it is seldom worth the effort to separate P-V relations into lung and chest wall components - the simpler alternative of studying only respiratory system P-V relations will give an adequate picture of lung mechanics, if the infant is deeply sedated and temporarily relaxed. The same is probably true also for older children. IV. High insufflation pressures will recruit otherwise collapsed airways, that will close early during the subsequent expiration. The relevance of this finding to conditions prevailing during regular breathing (mechanical or spontaneous) is, at most, speculative.
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44. |
- Zdolsek, Joachim, 1960-, et al.
(author)
-
Volume replacement/Joachim Boldt.
- 2004
-
In: Volume replacement. - Germany : UNI-MED Verlag AG. - 9783895997211 ; , s. -116
-
Book chapter (other academic/artistic)abstract
- "This book is not another attempt to create a ""cook book"" on volume replacement of fluid substitution. This book, in contrast, summarizes the up-to-date-knowledge of this topic presented by experts from a wide range of disciplines. Everybody caring for the critically ill will profit from the different chapters at different levels - nurses, students, residents, consultants, and even experts on volume therapy
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45. |
- Rostami, Elham, 1979-, et al.
(author)
-
Microdialysis in neurointensive care.
- 2004
-
In: Current pharmaceutical design. - : Bentham Science Publishers Ltd.. - 1381-6128 .- 1873-4286. ; 10:18, s. 2145-2152
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Journal article (peer-reviewed)abstract
- Microdialysis is a technique for sampling the chemistry of the interstitial fluid of tissues and organs in animal and man. It is minimally invasive and simple to perform in a clinical setting. Although microdialysis samples essentially all small molecular substances present in the interstitial fluid the use of microdialysis in neurointensive care has focused on markers of ischemia and cell damage. The lactate / pyruvate ratio is a well-known marker of changes in the redox state of cells caused by ischemia Glycerol is an integral component of cell membranes. Loss of energy due to ischemia eventually leads to an influx of calcium and a decomposition of cell membranes, which liberates glycerol into the interstitial fluid. Thus the lactate / pyruvate ratio and glycerol have become the most important markers of ischemia and cell membrane damage. While the primary insult at the site of the accident is beyond our control, secondary insults during intensive care should be avoided by all means. Therefore, the single most important finding from microdialysis studies is the dramatic difference in the vulnerability of the penumbra surrounding a lesion as compared to normal brain tissue allowing early detection of secondary insults after traumatic brain injury as well as the onset of vasospasm after subarachnoid hemorrhage.
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46. |
- Bentzer, Peter, et al.
(author)
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Infusion of prostacyclin following experimental brain injury in the rat reduces cortical lesion volume
- 2001
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In: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 18:3, s. 275-285
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Journal article (peer-reviewed)abstract
- Endothelial-derived prostacyclin is an important regulator of microvascular function, and its main actions are inhibition of platelet/leukocyte aggregation and adhesion, and vasodilation. Disturbances in endothelial integrity following traumatic brain injury (TBI) may result in insufficient prostacyclin production and participate in the pathophysiological sequelae of brain injury. The objective of this study was to evaluate the potential therapeutic effects of a low-dose prostacyclin infusion on cortical lesion volume, CA3 neuron survival and functional outcome following TBI in the rat. Anesthetized animals (sodium pentobarbital, 60 mg/kg, i.p.) were subjected to a lateral fluid percussion brain injury (2.5 atm) or sham injury. Following TBI, animals were randomized to receive a constant infusion of either prostacyclin (1 ng/kg x min(-1) i.v.) or vehicle over 48 h. All sham animals received vehicle (n = 6). Evaluation of neuromotor function, lesion volume, and CA3 neuronal loss was performed blindly. By 7 days postinjury, cortical lesion volume was significantly reduced by 43% in the prostacyclin-treated group as compared to the vehicle treated group (p < 0.01; n = 12 prostacyclin, n = 12 vehicle). No differences were observed in neuromotor function (48 h and 7 days following TBI), or in hippocampal cell loss (7 days following TBI) between the prostacyclin- and vehicle-treated groups. We conclude that prostacyclin in a low dose reduces loss of neocortical neurons following TBI and may be a potential clinical therapeutic agent to reduce neuronal cell death associated with brain trauma.
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47. |
- Bjursten, Henrik, et al.
(author)
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Elimination of S100B and renal function after cardiac surgery
- 2000
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In: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 14:6, s. 698-701
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Journal article (peer-reviewed)abstract
- OBJECTIVES: To determine the biologic half-life of the S100B protein and to investigate if the elimination of S100B depends on glomerular filtration rate (GFR). DESIGN: Prospective human study. SETTING: University hospital. PARTICIPANTS: Sixteen patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Shed mediastinal blood (autotransfusion) was returned to the patients postoperatively and used to study the kinetics of S100B. Iohexol was infused simultaneously to estimate GFR. S100B was measured at 0, 20, 40, 60, and 180 minutes after infusion. Iohexol was measured at 180 and 240 minutes after infusion. MEASUREMENTS AND MAIN RESULTS: S100B followed first-order kinetics, and the biologic half-life for S100B was determined to be 25.3 +/- 5.1 minutes. GFR was determined to be 63.8 +/- 34.4 mL/min. No correlation was found between GFR and S100B half-life. CONCLUSIONS: The elimination of S100B after cardiac surgery is faster than reported earlier and not affected by a moderate decrease in GFR. This finding is important when evaluating S100B levels after cardiac surgery.
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48. |
- Broome, Michael
(author)
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Simulation of cardiovascular physiology and pathology with CorVascSim : A PC software for advanced education and research
- 2004
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Other publication (other academic/artistic)abstract
- Background and Goal: The rapid development of computer technology makes simulation of cardiovascular physiology and pathology possible. The current work presents a scientifically based cardiovascular model, with a self-explanatory interface. Material and Methods: An electrical analogue of the cardiovascular system including resistances, capacitances and inductances was constructed. The contractile function of the cardiac atria and ventricles are represented by time-varying elastances. Valvular function, pericardial volume, ventricular interaction and intrathoracic pressure are represented by constants and functions, which can interact. Pressures, flows and volumes are recalculated every millisecond and presented on-line as numerical and high-resolution graphics. Results and Discussion: The validity of the simulation models is based on the references (1-4). The software makes it possible to illustrate a great diversity of circulatory pathological findings including systolic and diastolic heart failure, valve diseases, pericardial effusion, arteriosclerosis and effects of changes in intrathoracic pressure. The model is being used to educate doctors and nurses in cardiac surgery, cardiac anaesthesia, and cardiology, but its pedagogical value remains to be validated. Conclusion: Simulation of cardiac physiology and pathology provides a new way to study the heart. Results from simulations can be used in education as well as in interpretation of clinical invasive monitoring, echocardiography and experimental research.
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49. |
- Buer, Nina, 1960-, et al.
(author)
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Fear-avoidance beliefs and catastrophizing : occurrence and risk factor in back pain and ADL in the general population
- 2002
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In: Pain. - 0304-3959 .- 1872-6623. ; 99:3, s. 485-491
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Journal article (peer-reviewed)abstract
- Fear-avoidance beliefs and catastrophizing have been shown to be powerful cognitions in the process of developing chronic pain problems and there is a need for increased knowledge in early stages of pain.The objectives of this study were therefore, firstly, to examine the occurrence of fear-avoidance beliefs and catastrophizing in groups with different degrees of non-chronic spinal pain in a general population, and secondly to assess if fear-avoidance beliefs and catastrophizing were related to current ratings of pain and activities of daily living (ADL).The study was a part of a population based back pain project and the study sample consisted of 917 men and women, 35-45 years old, either pain-free or with non-chronic spinal pain. The results showed that fear-avoidance beliefs as well as catastrophizing occur in this general population of non-patients. The levels were moderate and in catastrophizing a 'dose-response' pattern was seen, such that more the catastrophizing was, the more was pain. The study showed two relationships, which were between fear-avoidance and ADL as well as between catastrophizing and pain intensity. Logistic regression analyses were performed with 95% confidence intervals and the odds ratio for fear-avoidance beliefs and ADL was 2.5 and for catastrophizing and pain 1.8, both with confidence interval above unity. The results suggest that fear-avoidance beliefs and catastrophizing may play an active part in the transition from acute to chronic pain and clinical implications include screening and early intervention. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.
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50. |
- Bång, Angela
(author)
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Emergency medical dispatch. The first medical response for life-threatening conditions. Assessment and invention of patients with chest pain and/or suspected cardiac arrest
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Aims: To describe the Emergency Medical Dispatcher's (EMDs) possibility of assessment and intervention of patients reported having chest pain and/or cardiac arrest, with regard to identification of the problem, priority-decision, provision of instructions in dispatcher-assisted bystander cardiopulmonary resuscitation (CPR), and the subsequent outcome in terms of final diagnosis and survival. Methods: Prospective and retrospective observational studies based on registrations made by EMDs in case record forms (during two months, 1993), and in the dispatch protocol (27 months, 1994-1996) and subsequent follow-up in ambulance and hospital files. Evaluations of tape recordings of emergency calls to the EMS dispatch centre, concerning patients treated for out-of-hospital cardiac arrest (99 calls/1986, 100 calls/2000-2001). A qualitative study was used to describe the EMDs perceptions of identifying cardiac arrest, offer and provide instructions in CPR to callers. Ten EMDs were approached for face-to-face interviews in 1997. Results: Among 503 patients reporting chest pain, 68% were judged as having severe chest pain, of which 26% developed acute myocardial infarction (AMI) as compared with 13% among patients judged as having only vague chest pain (p = 0.0004). The EMDs had a strong suspicion of AMI in 36%, a moderate suspicion of AMI in 34%, and a vague or no suspicion in 30%. Among patients with a strong suspicion of AMI, 29% subsequently developed AMI compared with 18% among patients with a moderate suspicion, and 15% among patients with only a vague or no suspicion of AMI (p< 0.001). The study sample size was too small to evaluate the predictive value of various associated symptoms accompanying chest pain. The priority level was similar in patients with and without a life-threatening condition (81% vs. 73% receiving the highest priority). In patients with cardiac arrest outside hospital, more attention should be paid to the detection of these patients by the EMDs, however, when the EMDs had a suspicion, their accuracy was high. Half of witnesses accepted an offer of instructions in CPR, and one-third completed dispatcher-assisted bystander CPR. The comparison between no performance and performance of dispatcher-assisted bystander CPR, suggests an increase in survival from 6% to 9%. Among suspected cardiac arrest cases, EMDs offer CPR instruction to only a small fraction of callers, with an accomplishment in all, of ~8%. However, 30-50% of suspected cardiac arrest cases seemed eligible to be approached with such an offer. A major obstacle was the presentation of suspected agonal breathing, which was estimated to occur in about 30%, and was described as: difficulties breathing, poorly, gasping, wheezing, impaired and occasional breathing. The EMDs have a belief that they are being an empathic authority that relieves the caller of the burden of responsibility, and by meeting the witness mentally, this may enable the caller to act at the scene. The EMDs are dependent on the callers knowledge and trustworthiness, and convincing answers from the caller prompt a more secure feeling in the EMDs, just as caller's lack of knowledge having a negative effect on the EMDs efforts. Conclusion: There was a strong relationship between the EMDs suspicion of AMI and subsequent development of AMI. One-third, however, developed AMI among those where the EMD had had a moderate, vague or no suspicion of AMI. Patients judged to have severe chest pain, developed AMI twice as often as patients judged to have vague pain. Caller's reporting patients with a combination of unconsciousness and agonal breathing or respiratory arrest should be offered dispatcher-assisted CPR instruction. This may improve survival in out-of hospital cardiac arrest.
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