| 1. |
- Axelsson, Birger, 1957-
(författare)
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Cardiac effects of non-adrenergic inotropic drugs : clinical and experimental studies
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Myocardial failure and dysfunction is not uncommon during critical illness and following cardiac surgery. For optimal treatment, a better understanding of the effects of inotropic drugs is needed. In this thesis, two non-adrenergic mediated inotropes, milrinone and levosimendan were studied in different models of myocardial dysfunction. The study aims were to assess the following: the effects of milrinone on blood flow in coronary artery bypass grafts during CABG surgery; the effects of milrinone on left ventricular diastolic function during post-ischaemic myocardial dysfunction; whether milrinone or levosimendan are protective or injurious during acute myocardial ischaemia, and if levosimendan potentiates myocardial function when added to milrinone in an experimental model of post-ischaemic (stunned) myocardium.Material and Methods: In Study I, 44 patients undergoing coronary artery bypass surgery(CABG) were included as subjects. Milrinone or saline was administrated in a single dose during cardio-pulmonary bypass (CPB) and coronary graft flow measurements were recorded after 10 and 30 min following CPB. In Study II; 24 patients undergoing CABG had estimations of peak ventricular filling rates made before and after CPB with administration of milrinone or saline as a single dose during CPB, performed by assessment of the rate of change in diastolic cross-sectional left ventricular area. In Study III, energy-metabolic effects of milrinone and levosimendan were measured in an anaesthetized porcine model during 45 minutes of regional myocardial ischemia. Microdialysis sampling of metabolites of local ischemic metabolism allowed assessment of glycolytic activity and the degree of myocardial calcium overload. In Study IV, in a porcine model of postischaemic myocardial stunning, ventricular pressure-volume relationships were analyzed when milrinone or a combination of milrinone and levosimendan were given together.Results: In Study I, there was a clear increase in non-sequential saphenous vein graft blood flow with milrinone at 10 minutes (64.5 ± 37.4 compared to placebo 43.6 ± 25.7 ml/min (mean ± SD).). A decreasing but still measureable flow increase was seen for milrinone at 30 minutes. In Study II, an increase in early left ventricular filling rate (ventricular cross-sectional area rate of change,dA/dt) was seen in the milrinone treated group. Pre-bypass milrinone group dA/dt 22.0 ± 9.5 changed to post-bypass values dA/dt 27.8 ± 11.5 cm2/sec). Placebo group pre-bypass dA/dt was 21.0 ± 8.7 and post-bypass 17.1 ± 7.1 cm2/sec. A milrinone effect was demonstrated in an adjusted regression model (p = 0.001). In Study III, neither milrinone nor levosimendan led to a change in energy-metabolic activity during ischemia as reflected by interstitial glucose, pyruvate, lactate orglycerol. Neither drug exacerbated the relative myocardial calcium overload during ischemia. In Study IV, milrinone improved active relaxation (tau) in post-ischemic stunned myocardium, but did not markedly improve systolic function by preload recruitable stroke work. Levosimendan added to milrinone showed minimal effect on active relaxation but a positive effect on systolic function in combination with milrinone.Conclusions: We conclude that milrinone treatment leads to an increase in blood flow in newly implanted coronary saphenous vein grafts, and improves ventricular relaxation post-cardiopulmonary bypass. Neither milrinone nor levosimendan, in this porcine model, negatively influence myocardial energy metabolism or calcium overload during acute ischaemia. Addition of levosimendan to milrinone treatment during post-ischaemic ventricular dysfunction may provide additive inotropic effects on systolic function but probably not for active relaxation.
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| 2. |
- Axelsson, Birger, 1957-, et al.
(författare)
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Milrinone and levosimendan during porcine myocardial ischemia : no effects on calcium overload and metabolism
- 2013
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Ingår i: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 57:6, s. 719-728
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia.Methods: Anaesthetised juvenile pigs, average weight 36kg, were randomised to one of three intravenous treatment groups: milrinone 50g/kg bolus plus infusion 0.5g/kg/min (n=7), levosimendan 24g/kg plus infusion 0.2g/kg/min (n=7), or placebo (n=6) for 60min prior to and during a 45min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. 45Ca2+ was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for 45Ca2+ recovery.Results: During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable.Conclusions: These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium.
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| 3. |
- Bastami, Salumeh, et al.
(författare)
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Influence of UGT2B7, OPRM1 and ABCB1 Gene Polymorphisms on Postoperative Morphine Consumption
- 2014
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 115:5, s. 423-431
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Tidskriftsartikel (refereegranskat)abstract
- Therapeutic modulation of pain with morphine and other opioids is associated with significant variation in both effects and adverse effects in individual patients. Many factors including gene polymorphisms have been shown to contribute to the interindividual variability in the response to opioids. The aim of this study was to investigate the significance of UGT2B7,OPRM1 and ABCB1 polymorphisms for interindividual variability in morphine-induced analgesia in patients undergoing hysterectomy. The frequency of these polymorphisms was also investigated in forensic autopsies as morphine is also a very commonly abused drug. Blood samples were collected from 40 patients following abdominal hysterectomy, 24hr after initiation of analgesia through a patient-controlled analgesia (PCA) pump. Samples were genotyped and analysed for morphine and its metabolites. We also genotyped approximately 200 autopsies found positive for morphine in routine forensic analysis. Patients homozygous for UGT2B7 802C needed significantly lower dose of morphine for pain relief. The same trend was observed for patients homozygous for ABCB1 1236T and 3435T, as well as to OPRM1 118A. The dose of morphine in patients included in this study was significantly related to variation in UGT2B7 T802C. Age was significantly related to both dose and concentration of morphine in blood. Regression analysis showed that 30% of differences in variation in morphine dose could be explained by SNPs in these genes. The genotype distribution was similar between the forensic cases and the patients. However, the mean concentration of morphine was higher in forensic cases compared to patients. We conclude that gene polymorphisms contribute significantly to the variation in morphine concentrations observed in individual patients.
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| 4. |
- Darvish, Bijan, 1969-, et al.
(författare)
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Management of accidental dural puncture and post-dural puncture headache after labour : a Nordic survey
- 2011
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Ingår i: Acta Anaesthesiologica Scandinavica. - : The Acta Anaesthesiologica Scandinavica Foundation. - 0001-5172 .- 1399-6576. ; 55:1, s. 46-53
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Tidskriftsartikel (refereegranskat)abstract
- Background: A major risk with epidural analgesia is accidental dural puncture (ADP), which may result in post-dural puncture headache (PDPH). This survey was conducted to explore the incidence of ADP, the policy for management of PDPH and the educational practices in epidural analgesia during labour in the Nordic countries.Methods: A postal questionnaire was sent to the anaesthesiologist responsible for Obstetric anaesthesia service in all maternity units (n=153) with questions relating to the year 2008.Results: The overall response rate was 93%. About 32% (22-47%) of parturients received epidural analgesia for labour. There were databases for registering obstetric epidural complications in 13% of Danish, 24% of Norwegian and Swedish, 43% of Finnish and 100% of hospitals in Iceland. The estimated incidence of ADP was 1% (n approximate to 900). Epidural blood patch (EBP) was performed in 86% (n approximate to 780) of the parturients. The most common time interval from diagnosis to performing EBP was 24-48 h. The success rate for EBP was > 75% in 67% (62-79%) of hospitals. The use of diagnostic CT/MRI before the first or the second EBP was exceptional. No major complication was reported. Teaching of epidurals was commonest (86%) in the non-obstetric population and 53% hospitals desired a formal training programme in obstetric analgesia.Conclusion: We found the incidence of ADP to be approximately 1%. EBP was the commonest method used for its management, and the success rate was high in most hospitals. Formal training in epidural analgesia was absent in most countries and trainees first performed it in the non-obstetric population.
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| 5. |
- Essving, Per, 1960-, et al.
(författare)
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Local Infiltration Analgesia Versus Intrathecal Morphine for Postoperative Pain Management After Total Knee Arthroplasty : A Randomized Controlled Trial
- 2011
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Ingår i: Anesthesia and Analgesia. - : Lippincott, Williams and Wilkins. - 0003-2999 .- 1526-7598. ; 113:4, s. 926-933
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Local infiltration analgesia (LIA)-using a combination of local anesthetics, nonsteroidal anti-inflammatory drugs, and epinephrine, injected periarticularly during surgery-has become popular in postoperative pain management after total knee arthroplasty (TKA). We compared intrathecal morphine with LIA after TKA. less thanbrgreater than less thanbrgreater thanMETHODS: In this double-blind study, 50 patients scheduled to undergo TKA under spinal anesthesia were randomized into 2 groups: group M, 0.1 mg morphine was injected intrathecally together with the spinal anesthetic and in group L, LIA using ropivacaine, ketorolac, and epinephrine was infiltrated in the knee during the operation, and 2 bolus injections of the same mixture were given via an intraarticular catheter postoperatively. Postoperative pain, rescue analgesic requirements, mobilization, and home readiness were recorded. Patient-assessed health quality was recorded using the Oxford Knee Score and EQ-5D during 3 months follow-up. The primary endpoint was IV morphine consumption the first 48 postoperative hours. less thanbrgreater than less thanbrgreater thanRESULTS: Mean morphine consumption was significantly lower in group L than in group M during the first 48 postoperative hours: 26 +/- 15 vs 54 +/- 29 mg, i.e., a mean difference for each 24-hour period of 14.2 (95% confidence interval [CI] 7.6 to 20.9) mg. Pain scores at rest and on movement were lower during the first 48 hours in group L than in group M (P andlt; 0.001). Pain score was also lower when walking in group L than in group M at 24 hours and 48 hours postoperatively (P andlt; 0.001). In group L, more patients were able to climb stairs at 24 hours: 50% (11 of 22) versus 4% (1 of 23), i.e., a difference of 46% (95% CI 23.5 to 68.5) and at 48 hours: 70% (16 of 23) versus 22% (5 of 23), i.e., a difference of 48% (95% CI 23 to 73). Median (range) time to fulfillment of discharge criteria was shorter in group L than in group M, 51 (24-166) hours versus 72 (51-170) hours. The difference was 23 (95% CI 18 to 42) hours (P = 0.001). Length of hospital stay was also shorter in group L than in group M: median (range) 3 (2-17) versus 4 (2-14) days (P = 0.029). Patient satisfaction was greater in group L than in group M (P = 0.001), but no differences were found in knee function, side effects, or in patient-related outcomes, Oxford Knee score, or EQ-5D. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: LIA technique provided better postoperative analgesia and earlier mobilization, resulting in shorter hospital stay, than did intrathecal morphine after TKA.
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| 6. |
- Essving, Per, 1960-, et al.
(författare)
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Minimally invasive surgery did not improve outcome compared to conventional surgery following unicompartmental knee arthroplasty using local infiltration analgesia A randomized controlled trial with 40 patients
- 2012
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Ingår i: Acta Orthopaedica. - New York, USA : Informa Healthcare. - 1745-3674 .- 1745-3682. ; 83:6, s. 634-641
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: There has recently been interest in the advantages of minimally invasive surgery (MIS) over conventional surgery, and on local infiltration analgesia (LIA) during knee arthroplasty. In this randomized controlled trial, we investigated whether MIS would result in earlier home-readiness and reduced postoperative pain compared to conventional unicompartmental knee arthroplasty (UKA) where both groups received LIA.Patients and methods: 40 patients scheduled for UKA were randomized to a MIS group or a conventional surgery (CON) group. Both groups received LIA with a mixture of ropivacaine, ketorolac, and epinephrine given intra-and postoperatively. The primary endpoint was home-readiness (time to fulfillment of discharge criteria). The patients were followed for 6 months.Results: We found no statistically significant difference in home-readiness between the MIS group (median (range) 24 (21-71) hours) and the CON group (24 (21-46) hours). No statistically significant differences between the groups were found in the secondary endpoints pain intensity, morphine consumption, knee function, hospital stay, patient satisfaction, Oxford knee score, and EQ-5D. The side effects were also similar in the two groups, except for a higher incidence of nausea on the second postoperative day in the MIS group.Interpretation: Minimally invasive surgery did not improve outcome after unicompartmental knee arthroplasty compared to conventional surgery, when both groups received local infiltration analgesia. The surgical approach (MIS or conventional surgery) should be selected according to the surgeon's preferences and local hospital policies.
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| 7. |
- Essving, Per, 1960-, et al.
(författare)
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Reduced morphine consumption and pain intensity with local infiltration analgesia (LIA) following total knee arthroplasty : a randomized double-blind study involving 48 patients
- 2010
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 81:3, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Postoperative pain is often severe following total knee arthroplasty (TKA). We investigated the efficacy of local infiltration analgesia (LIA) technique, intra- and postoperatively.Methods: 48 patients undergoing TKA were randomized into 2 groups in a double-blind study. In group A, 400 mg ropivacaine, 30 mg ketorolac and 0.5 mg epinephrine were infiltrated periarticularly intra-operatively. In group P, no injections were given. At 21 hours postoperatively, 200 mg ropivacaine, 30 mg ketorolac and 0.1 mg epinephrine were injected intraarticularly in group A, and the same volume of saline was injected in group P. Patients were followed up for 3 months.Results: Median morphine consumption was lower in group A during 0-48 h: 18 (1-74) mg vs. 87 (36-160) mg in group P. Postoperative pain was lower at rest in group A during the first 27 h, and on movement during the first 48 h, except at 21 h. Time to fulfilling discharge criteria was shorter in group A than in group P; 3 (1-7) vs. 5 (2-8) days. Patient satisfaction was higher in group A compared to group P on day 1 and 7. The unbound venous blood concentration of ropivacaine was below systemic toxic blood concentrations. Interpretation: Local infiltration analgesia (LIA) technique provides excellent pain relief and lower morphine consumption following TKA, resulting in shorter time to home readiness and higher patient satisfaction. Side effects were few and systemic LA concentrations low.
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| 8. |
- Fant, Federica, 1972-
(författare)
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Optimization of the perioperative anaesthetic care for prostate cancer surgery : clinical studies on pain, stress response and immunomodulation
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Prostate cancer (PC) is the most common cancer form in men. Surgery is the treatment of choice for localized form of PC and half of all surgical procedures are radical retropubic prostatectomies (RRP). In the first two studies, we compared the efficacy of thoracic epidural analgesia to patientcontrolled analgesia (PCA) with intravenous morphine (I) and to patientcontrolled local analgesia by intra-abdominal injection of local anaesthetic(LA) (II) in treating postoperative pain after RRP. In studies III and IV we evaluated the effects of thoracic epidural analgesia compared to PCA with morphine in reducing the surgical stress reaction, inflammatory response (III) as well as the immune suppression (IV) following RRP. In studies I and II, we found better pain relief both at rest and on coughing, lower morphine consumption and better respiratory function postoperatively in patients having epidural analgesia. However, we did not register differences in time to home readiness or length of hospital stay. Painmanagement did not significantly affect health-related quality of life. In study III, early surgical stress response (plasma glucose and cortisol) was reduced two hours after the skin incision in patients having epidural analgesia compared with those having intravenous morphine analgesia but no differences in inflammatory mediators were seen except IL-17 which was lower in the epidural group. In study IV, no differences were found between epidural and PCA groups in leucocyte subpopulations, immunecell activation after mitogen stimulation or in natural killer cell cytotoxicityas a measure of innate immunity. We observed a low incidence of side effects and postoperative complications in all studies with no differences between the groups. In summary, thoracic epidural analgesia provided better postoperative pain relief, improved respiratory function and reduction in early stress response to radical retropubic prostatectomy, without any significant effects on inflammation or immune suppression.
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| 9. |
- Fant, F., et al.
(författare)
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Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy
- 2013
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Ingår i: British Journal of Anaesthesia. - Oxford, USA : Oxford University Press. - 0007-0912 .- 1471-6771. ; 110:5, s. 747-757
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Tidskriftsartikel (refereegranskat)abstract
- Background: Epidural anaesthesia and analgesia has been shown to suppress the neurohormonal stress response, but its role in the inflammatory response is unclear. The primary aim was to assess whether the choice of analgesic technique influences these processes in patients undergoing radical retropubic prostatectomy.Methods: Twenty-six patients were randomized to Group P (systemic opioid-based analgesia) or Group E (thoracic epidural-based analgesia) perioperatively. Induction and maintenance of anaesthesia followed a standardized protocol. The following measurements were made perioperatively: plasma cortisol, glucose, insulin, C-reactive proteins, leucocyte count, plasma cytokines [interleukin (IL)-6, tumour necrosis factor (TNF)-alpha], and pokeweed mitogen-stimulated cytokines [interferon (IFN)-gamma, IL-2, IL-12p70, IL-10, IL-4, and IL-17]. Other parameters recorded were pain, morphine consumption, and perioperative complications.Results: Plasma concentration of cortisol and glucose were significantly higher in Group P compared with Group E at the end of surgery, the mean difference was 232 nmol litre(-1) [95% confidence interval (CI) 84-381] (P=0.004) and 1.6 mmol litre(-1) (95% CI 0.6-2.5) (P=0.003), respectively. No significant differences were seen in IL-6 and TNF-alpha at 24 h (P=0.953 and 0.368, respectively) and at 72 h (P=0.931 and 0.691, respectively). IL-17 was higher in Group P compared with Group E, both at 24 h (P=0.001) and 72 h (P=0.018) after operation. Pain intensity was significantly greater in Group P compared with Group E (P<0.05) up to 24 h.Conclusions: In this small prospective randomized study, thoracic epidural analgesia reduced the early postoperative stress response but not the acute inflammatory response after radical retrobupic prostatectomy, suggesting that other pathways are involved during the acute phase reaction.
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| 10. |
- Fant, Federica, et al.
(författare)
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Thoracic epidural analgesia or patient-controlled local analgesia for radical retropubic prostatectomy: a randomized, double-blind study
- 2011
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Ingår i: British Journal of Anaesthesia. - : Oxford University Press (OUP). - 0007-0912 .- 1471-6771. ; 107:5, s. 782-789
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Tidskriftsartikel (refereegranskat)abstract
- Background. Postoperative pain after radical retropubic prostatectomy is moderate to severe. The primary aim of this study was to assess whether intra-abdominal local anaesthetics provide similar analgesia compared with thoracic epidural analgesia (TEA). less thanbrgreater than less thanbrgreater thanMethods. Fifty patients, ASA I-II, participated in this prospective, double-blinded study. All patients had TEA. After operation, they were randomized into two groups of 25 patients: Group PCLA (patient-controlled local analgesia): self-administration of 10 ml of ropivacaine 2 mg ml(-1) via the intra-abdominal catheter for 48 h. Group TEA: infusion of 10 ml h(-1) of ropivacaine 1 mg ml(-1), fentanyl 2 mg ml(-1), and epinephrine 2 mg ml 21 epidurally for 48 h. The primary endpoint was pain on coughing at 4 h after operation. Rescue medication was morphine i.v. as required. less thanbrgreater than less thanbrgreater thanResults. Pain on coughing at 4, 24, and 48 h was significantly lower in Group TEA [0 (0-10)] compared with Group PCLA [4 (0-10)] (Pandlt;0.05). Significantly lower pain intensity was also found in Group TEA compared with Group PCLA at the incision site, deep pain, and pain on coughing at 4 and 24 h (Pandlt;0.05). Morphine consumption was significantly greater in Group PCLA [12 (0-46)] compared with Group TEA [0 (0-20)] at 0-48 h after operation [median (range)] (P=0.015). Maximum expiratory pressure was higher in Group TEA compared with Group PCLA at 24 h (Pandlt;0.01). less thanbrgreater than less thanbrgreater thanConclusions. TEA provides superior postoperative pain relief with better preservation of expiratory muscle strength compared with PCLA.
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