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- Bromfalk, Åsa, 1967-
(författare)
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Intervention for prevention : easing children’s preoperative anxiety
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Preoperative anxiety in children is associated with several adverse outcomes and consequences that can have a negative impact on the perioperative outcome and delay recovery. Anxiety can cause stress-induced cardiorespiratory instability, increased postoperative pain, nausea, emergence delirium, and long-term behavior changes. The ideal premedication for children is still debated. Only a few studies have examined the use of premedication in relation to total intravenous anesthesia (TIVA), and there is also a lack of studies exploring staff’s experiences of premedication. The aim of this thesis was to compare midazolam (a benzodiazepine), clonidine, and dexmedetomidine (a2-agonists) given as premedication to preschool children, regarding anxiety, cardiorespiratory response to sedation, time to postoperative recovery, posthospital negative behavior changes (NBCs), and staff’s experiences of the interventions.Methods: In a randomized clinical trial, 90 children aged 2–6 years, scheduled for TIVA and ear, nose, and throat surgery, were randomized to one of three groups, receiving midazolam 0.5 mg/kg, clonidine 4 mg/kg, or dexmedetomidine 2 mg/kg. The children were included at a 200-bed county hospital in northern Sweden and observed with validated tools from the day of surgery until two weeks postoperatively (Studies I–IV). To explore the clinical aspects, we conducted focus group interviews to elicit perioperative staff’s experiences of the studied interventions and analyzed the data with qualitative content analysis (Study V). Results: Midazolam reduced preoperative anxiety and provided perioperative cardiorespiratory stability. Clonidine and dexmedetomidine provided deeper sedation along with a minor decrease in heart rate. Some children, mainly from the clonidine group, awoke during the preoperative preparation, triggering anxiety, while the midazolam group remained conscious, calm, and cooperative. Postoperatively, the midazolam group emerged earlier from anesthesia compared to the two a2-agonist groups. However, the midazolam group had more episodes of postoperative anxiety, delirium, and pain compared to both groups receiving a2-agonists, and the overall recovery and discharge time from the post-anesthesia care unit was thus the same for all groups. The posthospital study showed at least one NBC in half of the children during the first two weeks after surgery. The staff’s experiences of premedication could be summarized in three themes: a matter of time, covering the efforts of building trust along with timing the administration and onset; don’t wake the sleeping bear, covering the challenge of maintaining sleep in the sleeping child in order to avoid a backlash if woken; and on responsive tiptoes, covering safety precautions and ethical perspectives on the interventions.Conclusion: The different premedications varied in their ability to reduce anxiety and to induce sleep, and this manifested itself throughout the perioperative process. Short-acting midazolam reduced preoperative anxiety but did not provide adequate sleep, and early postoperative emergence occasionally caused a rise in adverse symptom intensification. The long-lasting and sleep-inducing a2-agonists showed an unsatisfactory anxiolytic effect in comparison to midazolam. The sleep was superficial, and an awakening risked triggering anxiety. The staff strove to keep the sedated child asleep, and the recovery time was better and more peaceful when the children slept for a long time postoperatively. However, despite a calm perioperative process, one in two children presented with posthospital NBC. At the doses used in this study, all these premedications seem to be safe in cardiorespiratory terms, and the decision of which one to use should be tailored by individual and time.
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| 2. |
- Tydén, Jonas, 1973-
(författare)
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Heparin-binding protein and organ failure in critical illness
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: For patients severely ill enough to require care in an intensive care unit (ICU), both the disease itself (e.g. bacteria in the blood in sepsis or fractures after trauma) and effects of the immune system can cause circulatory, pulmonary, or renal dysfunction. Leukocytes play a dominant role in the immune system. When activated they release a range of small proteins with different properties Heparin-binding protein (HBP) being one of these proteins, has many functions, including to increase vascular permeability. Heparin-binding protein causes plasma leakage from blood vessels into surrounding tissue (oedema), which can lead to organ dysfunction depending on the site and degree of oedema formation. Increased concentration of HBP in plasma is associated with failing circulation and lung function in subgroups of critically ill patients.Aims: We investigated the possibility of using concentration of HBP in plasma for predicting circulatory, respiratory or renal failure in an ICU population with mixed diagnosis. We assessed concentration of HBP in alveoli in ventilator induced lung injury (VILI), and finally assessed elimination of HBP in urine and effluent fluid from continuous dialysis.Methods: In Papers I and II, HBP concentration in plasma was measured in 278 patients on admission to ICU. Sequential organ failure assessment (SOFA) scores and acute kidney injury (AKI) stage were recorded daily. In Paper III HBP concentration in bronco-alveolar fluid was measured in a pig model of ventilatory induced lung injury, in 16 healthy volunteers and in 10 intubated ICU patients. In Paper IV plasma and urine concentration of HBP was measured in 8 healthy volunteers and 20 burn ICU patients. In addition, HBP was sampled in plasma and effluent fluid in 32 ICU patients on continuous renal replacement therapy (CRRT).Results: In Paper I, patients developing circulatory failure (circulatory sub-score of SOFA = 4) had higher plasma concentration of HBP compared to those who did not (median(IQR)ng/ml) (63.5(32–105) vs 36.4(24–59)) p<0.01), and patients developing respiratory failure (P:F ratio < 27) had higher HBP concentration than those who did not (44.4(30-109) vs 35.2(23-57) p<0.01). Discriminatory capacity was (ROC AUC (95%CI)) (0.65 (0.54–0.76)) for circulatory failure and (0.61(0.54–0.69)) for respiratory failure. In Paper II, patients developing renal failure (AKI stage 2-3) had higher plasma concentration of HBP compared to those who did not (72.1 (13.0–131.2) vs 34.5 (19.7–49.3) p<0.01). Discriminatory capacity for AKI stage 3 was 0.68(0.54-0.83) (ROC AUC (95%CI)). In the subgroup with severe sepsis, it was 0.93 (0.85–1.00). In Paper III, HBP concentration in bronchoalveolar lavage was higher in pigs subjected to injurious ventilation over 6 hours ventilation compared to controls (1144(359–1636) vs 89(33–191) p=0.02) (median(IQR)ng/ml). The median HBP concentration in bronchoalveolar lavage from healthy volunteers was 0.90(0.79– 1.01) compared to 1959(612–3306) from intubated ICU patients (p < 0.01).In Paper IV, renal clearance of HBP was 0.19 (0.08-0.33) in healthy individuals and 0.30 (0.01-1.04) (median, IQR, ml/min) in burn ICU patients. Clearance of HBP was higher in burn patients with increased cystatin C (0.45(0.15-2.81) vs. 0.28(0.14-0.55) p=0.04). Starting CRRT did not alter plasma concentration of HBP (p=0.14). Median HBP concentration in effluent fluid on CRRT was 9.1 ng/ml (7.8-14.4).Conclusions: Papers I and II:There is an association between high concentration of HBP in plasma on ICU admission and circulatory, respiratory and renal failure. For the individual patient, the predictive value of a high HBP concentration is low, with the possible exception of renal failure in septic patients. Paper III:HBP concentration in alveoli increases in pigs subjected to injurious ventilation. HBP concentration in alveoli of intubated ICU patients ventilated protectively is elevated to similar levels, a factor of approximately 1000 times higher than the concentration seen in healthy controls. Paper IV:In healthy study participants, renal clearance of HBP is low. In critically ill burn patients with impaired renal function, clearance of HBP is increased. Starting CRRT in critically ill patients does not alter plasma concentration of HBP. Still, HBP is found in the CRRT effluent fluid, and concentration does not appear to be dependent on plasma concentration.
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| 3. |
- Walldén, Jakob, 1968-
(författare)
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The influence of opioids on gastric function : experimental and clinical studies
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Efter operation och anestesi får patienter ofta en negativ påverkan på magsäck och tarmar. Illamående och kräkningar är ett stort problem och många har svårt att komma igång med intag av föda och normal tarmfunktion då magsäcken och tarmarna ”står stilla”. Flera faktorer bidrar- bl.a. smärtan, det kirurgiska traumat och de läkemedel vi ger i samband med anestesin. Av de senare är opioider, d.v.s morfin och morfinliknande läkemedel, starkt bidragande. I detta avhandlings- arbete har opioiders effekter på magsäckens motilitet studerats. Med ett absorptionstest (paracetamolmetoden) studerades hos frivilliga hur opioiden remifentanil påverkar magsäckstömning och om kroppspositionen har betydelse för tömningshastigheten ut i tarmen. Remifentanil fördröjde magsäcks-tömningen och under pågående opioid behandling hade kroppspositionen ingen större betydelse, vilket det däremot hade under kontrollförsöken. Med samma metod jämförde vi hos patienter två anestesimetoder och studerade magsäcks-tömning direkt efter en operation. Ingen skillnad kunde påvisas mellan en opioidbaserad och en opioidfri anestesi, men inom respektive grupp var det en stor variation i magsäckstömning mellan individerna. Med en barostat studerades tonus i övre delen av magsäcken. Hos hälften av de frivilliga orsakade remifentanil en ökning av tonus och hos den andra hälften en minskning av tonus. Vidare undersöktes hos en grupp patienter opioiden fentanyls påverkan på den elektriska aktiviteten i magsäcken. Med en elekroga-strograf (EGG) registrerades de långsamma elektriska vågor som koordinerar muskelrörelserna i magsäcken. Hos hälften av de undersökta påverkades aktiviteten av fentanyl med en sänkt vågfrekvens eller upphörande av vågor, medan aktiviteten var opåverkad hos den övriga hälften. För att finna en förklaring till variationen gjordes genetiska analyser av genen för opioidreceptorn hos de undersökta i barostat och EGG studierna. Variationer i genomet, s.k. polymorfism, var inte associerad till utfallen i studierna. Studierna har visat på att opioider har en uttalad effekt på magsäckens motilitet och att den varierar kraftigt mellan individer. Polymorfism i genen för opioid- receptorn förklarade inte skillnaden mellan individer. Direkt efter operation bidrar sannolikt andra faktorer än anestesimetod till det variabla utfallet i magsäckstömning.
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