| 1. |
- Jalde, Francesca Campoccia, et al.
(författare)
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Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist : A Randomized Crossover Pilot Study
- 2018
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Ingår i: Anesthesiology. - 0003-3022 .- 1528-1175. ; 129:4, s. 769-777
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Tidskriftsartikel (refereegranskat)abstract
- Background: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. Methods: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. Results: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. Conclusions: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.
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| 2. |
- Sackey, Peter, et al.
(författare)
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Short- and long-term follow-up of intensive care unit patients after sedation with isoflurane and midazolam : A pilot study
- 2008
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 36:3, s. 801-806
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To compare memories from the intensive care unit (ICU) and short- and long-term psychological morbidity in patients after sedation with intravenous midazolam or inhaled isoflurane. DESIGN: Prospective long-term follow-up after randomized controlled trial. SETTING: General ICU at Karolinska University Hospital, Solna, Stockholm. PATIENTS: Forty patients in need of sedation during ventilator treatment. INTERVENTIONS: Patients were randomized to receive isoflurane or midazolam for goal-directed sedation until extubation or for a maximum of 96 hrs. MEASUREMENTS AND MAIN RESULTS: For short-term follow-up, doctors', nurses', and physiotherapists' notes from the 4 days following exposure to the study drugs were reviewed for words indicating adequate or pathologic cognitive and psychological recovery. For long-term follow-up, all 6-month survivors received questionnaires including the ICU Memory Tool (ICU-MT), Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), and Well-Being Index. Additionally, several screening questions for previous posttraumatic stress symptoms were included. In the short term follow-up, no significant differences were found between groups. In the long-term follow-up, a trend toward fewer hallucinations/delusions after isoflurane sedation than after midazolam (two of ten isoflurane patients vs. five of seven midazolam patients) was found (p = .06). None of the five solely isoflurane-sedated patients reported hallucinations/delusions from the ICU. There was no difference in groups in long-term psychological morbidity as measured with HADS and IES. Memories of negative feelings in the ICU (ICU-MT) were associated with high HADS and IES scores (Fisher's exact test, p = .02 and p = .01, respectively). CONCLUSIONS: Sedation of ICU patients with isoflurane may result in fewer delusional memories or hallucinations from the ICU compared with more commonly used intravenous sedation. Memories of negative feelings from the ICU were associated with symptoms of depression or anxiety or symptoms indicating posttraumatic stress disorder. Further study of memory and cognitive/psychological recovery after prolonged isoflurane sedation beyond 96 hrs is warranted.
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| 3. |
- Aare, Sudhakar, et al.
(författare)
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Mechanisms underlying the sparing of masticatory versus limb muscle function in an experimental critical illness model
- 2011
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 43:24, s. 1334-1350
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Tidskriftsartikel (refereegranskat)abstract
- Acute quadriplegic myopathy (AQM) is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients which is characterized by tetraplegia/generalized weakness of limb and trunk muscles. Masticatory muscles, on the other hand, are typically spared or less affected, yet the mechanisms underlying this striking muscle-specific difference remain unknown. This study aims to evaluate physiological parameters and the gene expression profiles of masticatory and limb muscles exposed to factors suggested to trigger AQM, such as mechanical ventilation, immobilization, neuromuscular blocking agents (NMBA), corticosteroids (CS) and sepsis for five days by using a unique porcine model mimicking the ICU conditions. Single muscle fiber cross-sectional area and force-generating capacity, i.e., maximum force normalized to fiber cross-sectional area (specific force), revealed maintained masseter single muscle fiber cross-sectional area and specific-force after five days exposure to all triggering factors. This is in sharp contrast to observations in limb and trunk muscles, showing a dramatic decline in specific force in response to five days exposure to the triggering factors. Significant differences in gene expression were observed between craniofacial and limb muscles, indicating a highly complex and muscle specific response involving transcription and growth factors, heat shock proteins, matrix metalloproteinase inhibitor, oxidative stress responsive elements and sarcomeric proteins underlying the relative sparing of cranial versus spinal nerve innervated muscles during exposure to the ICU intervention.
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| 4. |
- Aare, Sudhakar, et al.
(författare)
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The role of sepsis in the development of limb muscle weakness in a porcine intensive care unit model
- 2012
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 44:18, s. 865-877
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Tidskriftsartikel (refereegranskat)abstract
- Severe muscle wasting and loss of muscle function in critically ill mechanically ventilated intensive care unit (ICU) patients have significant negative consequences on their recovery and rehabilitation that persist long after their hospital discharge; moreover the underlying mechanisms are unclear. Mechanical ventilation (MV) and immobilization-induced modifications play an important role in these consequences, including endotoxin induced sepsis. The present study aims to investigate how sepsis aggravates ventilator and immobilization-related limb muscle dysfunction. Hence, biceps femoris muscle gene expression was investigated in pigs exposed to ICU intervention, i.e., immobilization, sedation, and MV, alone or in combination with sepsis for five days. In previous studies, we have shown that ICU intervention alone or in combination with sepsis did not affect muscle fiber size on day 5, but a significant decrease was observed in single fiber maximal force normalized to cross-sectional area (specific force) when sepsis was added to the ICU intervention. According to microarray data, the addition of sepsis to the ICU intervention induced a deregulation of more than 500 genes, such as an increased expression of genes involved in chemokine activity, kinase activity and transcriptional regulation. Genes involved in the regulation of the oxidative stress response, cytoskeletal/sarcomeric and heat shock proteins were on the other hand down-regulated when sepsis was added to the ICU intervention. Thus, sepsis has a significant negative effect on muscle function in critically ill ICU patients and chemokine activity and heat shock protein genes are forwarded to play an instrumental role in this specific muscle wasting condition.
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| 5. |
- Banduseela, Varuna C., et al.
(författare)
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Gene expression and muscle fiber function in a porcine ICU model
- 2009
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 39:3, s. 141-159
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle wasting and impaired muscle function in response to mechanical ventilation and immobilization in intensive care unit (ICU) patients are clinically challenging partly due to 1) the poorly understood intricate cellular and molecular networks and 2) the unavailability of an animal model mimicking this condition. By employing a unique porcine model mimicking the conditions in the ICU with long-term mechanical ventilation and immobilization, we have analyzed the expression profile of skeletal muscle biopsies taken at three time points during a 5-day period. Among the differentially regulated transcripts, extracellular matrix, energy metabolism, sarcomeric and LIM protein mRNA levels were downregulated, while ubiquitin proteasome system, cathepsins, oxidative stress responsive genes and heat shock proteins (HSP) mRNAs were upregulated. Despite 5 days of immobilization and mechanical ventilation single muscle fiber cross-sectional areas as well as the maximum force generating capacity at the single muscle fiber level were preserved. It is proposed that HSP induction in skeletal muscle is an inherent, primary, but temporary protective mechanism against protein degradation. To our knowledge, this is the first study that isolates the effect of immobilization and mechanical ventilation in an ICU condition from various other cofactors.
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| 6. |
- Banduseela, Varuna, et al.
(författare)
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Impaired autophagy, chaperone expression, and protein synthesis in response to critical illness interventions in porcine skeletal muscle
- 2013
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Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 45:12, s. 477-486
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Tidskriftsartikel (refereegranskat)abstract
- Critical illness myopathy (CIM) is characterized by a preferential loss of the motor protein myosin, muscle wasting, and impaired muscle function in critically ill intensive care unit (ICU) patients. CIM is associated with severe morbidity and mortality and has a significant negative socioeconomic effect. Neuromuscular blocking agents, corticosteroids, sepsis, mechanical ventilation, and immobilization have been implicated as important risk factors, but the causal relationship between CIM and the risk factors has not been established. A porcine ICU model has been used to determine the immediate molecular and cellular cascades that may contribute to the pathogenesis prior to myosin loss and extensive muscle wasting. Expression profiles have been compared between pigs exposed to the ICU interventions, i.e., mechanically ventilated, sedated, and immobilized for 5 days, with pigs exposed to critical illness interventions, i.e., neuromuscular blocking agents, corticosteroids, and induced sepsis in addition to the ICU interventions for 5 days. Impaired autophagy as well as impaired chaperone expression and protein synthesis were observed in the skeletal muscle in response to critical illness interventions. A novel finding in this study is impaired core autophagy machinery in response to critical illness interventions, which when in concert with downregulated chaperone expression and protein synthesis may collectively affect the proteostasis in skeletal muscle and may exacerbate the disease progression in CIM.
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| 7. |
- Gelberg, Jan, et al.
(författare)
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Improving survival and neurologic function for younger age groups after out-of-hospital cardiac arrest in Sweden : a 20-year comparison
- 2015
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Ingår i: Pediatric Critical Care Medicine. - 1529-7535 .- 1947-3893. ; 16:8, s. 750-757
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe changes in the epidemiology of out-of-hospital cardiac arrest in Sweden with the emphasis on the younger age groups.Design: Prospective observational study. Setting: Sweden.Patients: Patients were recruited from the Swedish Registry of Cardiopulmonary Resuscitation from 1990 to 2012. Only non-crew-witnessed cases were included.Intervention: Cardiopulmonary resuscitation.Measurement and Main Results: The endpoint was 30-day survival. Cerebral function among survivors was estimated according to the cerebral performance category scores. In all, 50,879 patients in the survey had an out-of-hospital cardiac arrest, of which 1,321 (2.6%) were 21 years old or younger and 1,543 (3.0%) were 22-35 years old. On the basis of results from 2011 and 2012, we estimated that there are 4.9 cases per 100,000 person-years in the age group 0-21 years. The highest survival was found in the 13- to 21-year age group (12.6%). Among patients 21 years old or younger, the following were associated with an increased chance of survival: increasing age, male gender, witnessed out-of-hospital cardiac arrest, ventricular-fibrillation, and a short emergency medical service response time. Among patients 21 years old or younger, there was an increase in survival from 6.2% in 1992-1998 to 14.0% in 2007-2012. Among 30-day survivors, 91% had a cerebral performance category score of 1 or 2 (good cerebral performance or moderate cerebral disability) at hospital discharge.Conclusions: In Sweden, among patients 21 years old or younger, five out-of-hospital cardiac arrests per 100,000 person-years occur and survival in this patient group has more than doubled during the past two decades. The majority of survivors have good or relatively good cerebral function.
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| 8. |
- Kalzén, Håkan, et al.
(författare)
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Unnecessary harm is avoided by reliable paediatric index of mortality2 scores without arterial gas sampling
- 2019
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:4, s. 670-675
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To investigate whether unnecessary harm could be avoided in children admitted to paediatric intensive care (PICU), we analysed the impact of arterial blood gas on the paediatric index of mortality score2 (PIM2) and the derived predicted death rate (PDR). Methods: From January 1, 2008 to December 31, 2010, 1793 consecutive admissions, newborn infants to 16 years of age (median 0.71 years) from a single, tertiary PICU in Gothenburg Sweden, were collected. Admission information on arterial oxygen tension (PaO2) and fraction of inspired oxygen (FiO2) was extracted from 990 admissions. Results: There was close agreement between PIM2 score and PDR regardless of whether the PaO2/FiO2 ratio was omitted or not. In the subgroup of admissions with a respiratory admission diagnosis, the inclusion of the PaO2/FiO2 ratio increased the accuracy of the PIM2 score as well as the PDR. The standard mortality ratio was slightly but not significantly overestimated by excluding the PaO2/FiO2 ratio. Conclusion: To avoid unnecessary harm to children admitted to PICU, an arterial blood gas analysis should only be performed if clinically indicated or if the child has a respiratory admission diagnosis. Estimation of the PIM2 score and PDR will not be less accurate by this approach.
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| 9. |
- Ochala, Julien, et al.
(författare)
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Diaphragm muscle weakness in an experimental porcine intensive care unit model
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
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Tidskriftsartikel (refereegranskat)abstract
- In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.
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| 10. |
- Ochala, Julien, et al.
(författare)
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EMD 57033 partially reverses ventilator-induced diaphragm muscle fibre calcium desensitisation
- 2010
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Ingår i: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 459:3, s. 475-483
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Tidskriftsartikel (refereegranskat)abstract
- In critically ill patients, ventilator-induced diaphragm muscle fibre dysfunction (VIDD) contributes to weaning problems, increasing hospitalisation time and related costs. VIDD pathophysiology remains partially unknown, especially the characterisation of the contractile dysfunction. In the present study, it was hypothesised that Ca(2+) activation is affected during VIDD. Ca(2+) sensitivity of contraction was therefore evaluated at the single skinned diaphragm muscle fibre level in piglets randomised into sham operation or 5-day mechanical ventilation. Ca(2+) sensitivities of force and stiffness in fibres were significantly impaired in all mechanically ventilated piglets compared with sham-operated controls, suggesting a less efficient Ca(2+) activation of cells, i.e. a lower relative number of strongly attached cross-bridges for each sub-maximal concentration of Ca(2+). In an attempt to test whether this negative effect of VIDD is reversible, single muscle fibres were exposed to the EMD 57033 Ca(2+) sensitiser. EMD 57033 (30 microM) improved the Ca(2+) sensitivity of force and stiffness in fibres from animals that were mechanically ventilated for 5 days as well as in sham-operated piglets. Thus, EMD 57033 partly restored the Ca(2+) activation of cells, reducing VIDD. This finding offers a strong basis for evaluating the effect of Ca(2+) sensitisers on diaphragm function in vivo.
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