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2.
Anesth Analg ; 130(2): 341-351, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30855340

RESUMO

BACKGROUND: Skeletal muscle failure in critical illness (intensive care unit-acquired weakness) is a well-known complication developing early during intensive care unit stay. However, muscle weakness during the perioperative setting has not yet been investigated. METHODS: We performed a subgroup investigation of a prospective observational trial to investigate perioperative muscle weakness. Eighty-nine patients aged 65 years or older were assessed for handgrip strength preoperatively, on the first postoperative day, at intensive care unit discharge, at hospital discharge, and at 3-month follow-up. Functional status was evaluated perioperatively via Barthel index, instrumental activities of daily living, Timed Up and Go test, and functional independence measure. After exclusion of patients with intensive care unit-acquired weakness or intensive care unit stay of ≥72 hours, 59 patients were included into our analyses. Of these, 14 patients had additional pulmonary function tests preoperatively and on postoperative day 1. Blood glucose was measured intraoperatively every 20 minutes. RESULTS: Handgrip strength significantly decreased after surgery on postoperative day 1 by 16.4% (P < .001). Postoperative pulmonary function significantly decreased by 13.1% for vital capacity (P = .022) and 12.6% for forced expiratory volume in 1 second (P = .001) on postoperative day 1. Handgrip strength remained significantly reduced at hospital discharge (P = .016) and at the 3-month follow-up (P = .012). Perioperative glucose levels showed no statistically significant impact on muscle weakness. Instrumental activities of daily living (P < .001) and functional independence measure (P < .001) were decreased at hospital discharge, while instrumental activities of daily living remained decreased at the 3-month follow-up (P = .026) compared to preoperative assessments. CONCLUSIONS: Perioperatively acquired weakness occurred, indicated by a postoperatively decreased handgrip strength, decreased respiratory muscle function, and impaired functional status, which partly remained up to 3 months.

3.
Crit Care ; 23(1): 308, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506074

RESUMO

BACKGROUND: Neuromuscular electrical stimulation (NMES) has been investigated as a preventative measure for intensive care unit-acquired weakness. Trial results remain contradictory and therefore inconclusive. As it has been shown that NMES does not necessarily lead to a contractile response, our aim was to characterise the response of critically ill patients to NMES and investigate potential outcome benefits of an adequate contractile response. METHODS: This is a sub-analysis of a randomised controlled trial investigating early muscle activating measures together with protocol-based physiotherapy in patients with a SOFA score ≥ 9 within the first 72 h after admission. Included patients received protocol-based physiotherapy twice daily for 20 min and NMES once daily for 20 min, bilaterally on eight muscle groups. Electrical current was increased up to 70 mA or until a contraction was detected visually or on palpation. Muscle strength was measured by a blinded assessor at the first adequate awakening and ICU discharge. RESULTS: One thousand eight hundred twenty-four neuromuscular electrical stimulations in 21 patients starting on day 3.0 (2.0/6.0) after ICU admission were included in this sub-analysis. Contractile response decreased from 64.4% on day 1 to 25.0% on day 7 with a significantly lower response rate in the lower extremities and proximal muscle groups. The electrical current required to elicit a contraction did not change over time (day 1, 50.2 [31.3/58.8] mA; day 7, 45.3 [38.0/57.5] mA). The electrical current necessary for a contractile response was higher in the lower extremities. At the first awakening, patients presented with significant weakness (3.2 [2.5/3.8] MRC score). When dividing the cohort into responders and non-responders (> 50% vs. ≤ 50% contractile response), we observed a significantly higher SOFA score in non-responders. The electrical current necessary for a muscle contraction in responders was significantly lower (38.0 [32.8/42.9] vs. 54.7 [51.3/56.0] mA, p < 0.001). Muscle strength showed higher values in the upper extremities of responders at ICU discharge (4.4 [4.1/4.6] vs. 3.3 [2.8/3.8] MRC score, p = 0.036). CONCLUSION: Patients show a differential contractile response to NMES, which appears to be dependent on the severity of illness and also relevant for potential outcome benefits. TRIAL REGISTRATION: ISRCTN ISRCTN19392591 , registered 17 February 2011.

4.
Ann Intensive Care ; 9(1): 100, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31486927

RESUMO

BACKGROUND: Serum potassium concentrations are commonly between 3.5 and 5.0 mmol/l. Standardised protocols for potassium range and supplementation in the ICU are lacking. The purpose of this retrospective analysis of ICU patients was to investigate potassium concentrations, variability and supplementation, and their association with in-hospital mortality. METHODS: ICU patients ≥ 18 years, with ≥ 2 serum potassium values, treated at the Charité - Universitätsmedizin Berlin between 2006 and 2018 were eligible for inclusion. We categorised into groups of mean potassium concentrations: < 3.0, 3.0-3.5, > 3.5-4.0, > 4.0-4.5, > 4.5-5.0, > 5.0-5.5, > 5.5 mmol/l and potassium variability: 1st, 2nd and ≥ 3rd standard deviation (SD). We analysed the association between the particular groups and in-hospital mortality and performed binary logistic regression analysis. Survival curves were performed according to Kaplan-Meier and tested by Log-Rank. In a subanalysis, the association between potassium supplementation and in-hospital mortality was investigated. RESULTS: In 53,248 ICU patients with 1,337,742 potassium values, the lowest mortality (3.7%) was observed in patients with mean potassium concentrations between > 3.5 and 4.0 mmol/l and a low potassium variability within the 1st SD. Binary logistic regression confirmed these results. In a subanalysis of 22,406 ICU patients (ICU admission: 2013-2018), 12,892 (57.5%) received oral and/or intravenous potassium supplementation. Potassium supplementation was associated with an increase in in-hospital mortality in potassium categories from > 3.5 to 4.5 mmol/l and in the 1st, 2nd and ≥ 3rd SD (p < 0.001 each). CONCLUSIONS: ICU patients may benefit from a target range between 3.5 and 4.0 mmol/l and a minimal potassium variability. Clear potassium target ranges have to be determined. Criteria for widely applied potassium supplementation should be critically discussed. Trial registration German Clinical Trials Register, DRKS00016411. Retrospectively registered 11 January 2019, http://www.drks.de/DRKS00016411.

5.
Minerva Anestesiol ; 85(11): 1201-1210, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31486622

RESUMO

BACKGROUND: Hyperglycemia frequently occurs during major surgery and is associated with adverse postoperative outcomes. This study aimed to investigate the influence of intraoperative hyperglycemia on incidences of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). METHODS: Eighty-seven patients aged ≥65 years undergoing elective surgery were included in this prospective observational subproject of the BioCog study. Blood glucose (BG) levels were measured every 20 minutes intraoperatively. Hyperglycemia was defined as BG levels ≥150 mg·dL-1. Patients were assessed for POD twice daily until postoperative day 7. The occurrence of POCD was determined three months after surgery. Multivariable logistic regression was used to identify associations between hyperglycemia and POD as well as POCD. Secondary endpoints comprised duration of hyperglycemia, maximum glucose level (Glucosemax) and differences between diabetic and non-diabetic patients. RESULTS: POD occurred in 41 (47.1%), POCD in five (15.2%) patients. In two separate multivariable logistic regression models, hyperglycemia was significantly associated with POD (OR 3.86 [CI 95% 1.13, 39.49], P=0.044) but not POCD (3.59 [NaN, NaN], P=0.157). Relative duration of hyperglycemia was higher in POD patients compared to patients without POD (20 [0; 71] % versus 0 [0; 55] %, P=0.075), whereas the maximum glucose levels during surgery were similar between the two groups. Considering only non-diabetic patients, relative duration of hyperglycemia (P=0.003) and Glucosemax (P=0.015) were significantly higher in patients with POD. CONCLUSIONS: Intraoperative hyperglycemia was independently associated with POD but not POCD. Relative duration of hyperglycemia appeared thereby to also play a role. Especially hyperglycemic non-diabetic patients might be at high risk for POD.

6.
Int J Med Sci ; 16(5): 665-674, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31217734

RESUMO

BACKGROUNDː Dysglycemia is associated with adverse outcome including increased morbidity and mortality in surgical patients. Acute insulin resistance due to the surgical stress response is seen as a major cause of so-called stress hyperglycemia. However, understanding of factors determining blood glucose (BG) during surgery is limited. Therefore, we investigated risk factors contributing to intraoperative dysglycemia. METHODSː In this subgroup investigation of the BIOCOG study, we analyzed 87 patients of ≥ 65 years with tight intraoperative BG measurement every 20 min during elective surgery. Dysglycemia was defined as at least one intraoperative BG measurement outside the recommended target range of 80-150 mg/dL. Additionally, all postoperative BG measurements in the ICU were obtained. Multivariable logistic regression analysis adjusted for age, sex, American Society of Anesthesiologists (ASA) status, diabetes, type and duration of surgery, minimum Hemoglobin (Hb) and mean intraoperative norepinephrine use was performed to identify risk factors of intraoperative dysglycemia. RESULTSː 46 (52.9%) out of 87 patients developed intraoperative dysglycemia. 31.8% of all intraoperative BG measurements were detected outside the target range. Diabetes [OR 9.263 (95% CI 2.492, 34.433); p=0.001] and duration of surgery [OR 1.005 (1.000, 1.010); p=0.036] were independently associated with the development of intraoperative dysglycemia. Patients who experienced intraoperative dysglycemia had significantly elevated postoperative mean (p<0.001) and maximum BG levels (p=0.001). Length of ICU (p=0.007) as well as hospital stay (p=0.012) were longer in patients with dysglycemia. CONCLUSIONSː Diabetes and duration of surgery were confirmed as independent risk factors for intraoperative dysglycemia, which was associated with adverse outcome. These patients, therefore, might require intensified glycemic control. Increased awareness and management of intraoperative dysglycemia is warranted.


Assuntos
Complicações do Diabetes/epidemiologia , Diabetes Mellitus/cirurgia , Hiperglicemia/epidemiologia , Complicações Intraoperatórias/epidemiologia , Idoso , Glicemia/metabolismo , Complicações do Diabetes/patologia , Complicações do Diabetes/cirurgia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Feminino , Humanos , Hiperglicemia/etiologia , Hiperglicemia/patologia , Hiperglicemia/cirurgia , Insulina/metabolismo , Resistência à Insulina/genética , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/patologia , Complicações Intraoperatórias/cirurgia , Masculino , Fatores de Risco
7.
J Cachexia Sarcopenia Muscle ; 10(4): 734-747, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31016887

RESUMO

BACKGROUND: Early mobilization improves physical independency of critically ill patients at hospital discharge in a general intensive care unit (ICU)-cohort. We aimed to investigate clinical and molecular benefits or detriments of early mobilization and muscle activating measures in a high-risk ICU-acquired weakness cohort. METHODS: Fifty patients with a SOFA score ≥9 within 72 h after ICU admission were randomized to muscle activating measures such as neuromuscular electrical stimulation or whole-body vibration in addition to early protocol-based physiotherapy (intervention) or early protocol-based physiotherapy alone (control). Muscle strength and function were assessed by Medical Research Council (MRC) score, handgrip strength and Functional Independence Measure at first awakening, ICU discharge, and 12 month follow-up. Patients underwent open surgical muscle biopsy on day 15. We investigated the impact of muscle activating measures in addition to early protocol-based physiotherapy on muscle strength and function as well as on muscle wasting, morphology, and homeostasis in patients with sepsis and ICU-acquired weakness. We compared the data with patients treated with common physiotherapeutic practice (CPP) earlier. RESULTS: ICU-acquired weakness occurs within the entire cohort, and muscle activating measures did not improve muscle strength or function at first awakening (MRC median [IQR]: CPP 3.3 [3.0-4.3]; control 3.0 [2.7-3.4]; intervention 3.0 [2.1-3.8]; P > 0.05 for all), ICU discharge (MRC median [IQR]: CPP 3.8 [3.4-4.4]; control 3.9 [3.3-4.0]; intervention 3.6 [2.8-4.0]; P > 0.05 for all), and 12 month follow-up (MRC median [IQR]: control 5.0 [4.3-5.0]; intervention 4.8 [4.3-5.0]; P = 0.342 for all). No signs of necrosis or inflammatory infiltration were present in the histological analysis. Myocyte cross-sectional area in the intervention group was significantly larger in comparison with the control group (type I +10%; type IIa +13%; type IIb +3%; P < 0.001 for all) and CPP (type I +36%; type IIa +49%; type IIb +65%; P < 0.001 for all). This increase was accompanied by an up-regulated gene expression for myosin heavy chains (fold change median [IQR]: MYH1 2.3 [1.1-2.7]; MYH2 0.7 [0.2-1.8]; MYH4 5.1 [2.2-15.3]) and an unaffected gene expression for TRIM63, TRIM62, and FBXO32. CONCLUSIONS: In our patients with sepsis syndrome at high risk for ICU-acquired weakness muscle activating measures in addition to early protocol-based physiotherapy did not improve muscle strength or function at first awakening, ICU discharge, or 12 month follow-up. Yet it prevented muscle atrophy.

8.
J Neuroimaging ; 29(2): 260-267, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30468268

RESUMO

BACKGROUND AND PURPOSE: In hyperglycemic patients, who succumbed to septic shock, an increased rate of apoptosis of microglial cells and damaged neurons of the hippocampus were found. However, the influence of perioperative glucose levels on hippocampal brain structures has not yet been investigated. METHODS: As part of the ongoing BIOCOG project, a subgroup of N = 65 elderly nondemented patients were analyzed who underwent elective surgery of ≥60 minutes. In these patients, at least one intraoperative blood glucose (BG) measurement was available from the medical charts. Intraoperative glucose maximum was determined in each patient. Preoperatively and at 3 months follow-up, structural neuroimaging was performed with T1-weighted magnetization prepared rapid gradient-echo sequence (MP-Rage) and a dedicated high-resolution hippocampus magnetic resonance imaging (MRI). The MRI scans were analyzed to assess pre- or postoperative volume changes of the hippocampus as a whole and hippocampal subfields. We also assessed changes of frontal lobe volume and cortical thickness. RESULTS: Overall, 173 intraoperative BG levels were obtained in 65 patients (median 2 per patient). A total of 18 patients showed intraoperative hyperglycemia (glucose maximum ≥150 mg/dL). Controlling for age and diabetes status, no significant impact of intraoperative hyperglycemia was found on the pre-post volume change of the hippocampus as a whole, hippocampal subfields, frontal lobe, and frontal cortical thickness. CONCLUSIONS: This study found no effect of intraoperative hyperglycemia on postoperative brain structures and volumes including volumes of hippocampus and hippocampal subfields, frontal lobe, and frontal cortical thickness. Further studies investigating the impact of intraoperatively elevated glucose levels should consider a tighter or even continuous glycemic measurement and the determination of central microglial activation.

9.
Anasthesiol Intensivmed Notfallmed Schmerzther ; 52(11-12): 785-797, 2017 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-29156482

RESUMO

Frail patients are more prone to develop complications during and after surgery. As the syndrome becomes more common, recognition and special management of frail patients in the perioperative setting is becoming crucial to improve short- and long-term outcomes. Based on current literature and guidelines, we present a compilation of strategies that could be employed to reduce postoperative complication rates in frail patients. Due to their impaired response to stressors, potential perioperative hazards to frail patients are identified and discussed. This includes the risk of dehydration, hypothermia, cardiovascular decompensation, unusual drug reactions, and delirium. The benefits of early mobilization and nutritional support are also discussed. If frailty is detected preoperatively, thus alerting the team about the increased risk of complications, strategies can be implemented in the perioperative setting to improve the chances of successful recovery.


Assuntos
Idoso Fragilizado , Fragilidade/terapia , Cuidados Pós-Operatórios , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Idoso , Idoso de 80 Anos ou mais , Fragilidade/diagnóstico , Avaliação Geriátrica , Humanos , Monitorização Intraoperatória
10.
Minerva Anestesiol ; 83(9): 921-929, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28256812

RESUMO

BACKGROUND: Hyperglycemia in hospitalized patients is associated with increased morbidity and mortality. Postoperative infections are particularly common in the setting of perioperative hyperglycemia; however, the relationship between perioperative glucose levels and the innate immune system remains unclear. METHODS: Immune cells, monocytic respectively T cell function and T cell subspecies of 32 patients after esophageal or pancreatic resection were analyzed preoperatively and on the first day after surgery (POD 1). Perioperative blood glucose was measured hourly via arterial blood gas analyses. Groups were classified by maximum perioperative glucose levels: <180 mg/dL versus at least one episode of ≥180 mg/dL. The suppression of immune cells and cytokines was defined as the difference between pre- and postoperative values. RESULTS: In perioperative hyperglycemic patients, preoperative CD4+/CD8+ ratio (P=0.039), count of CD4+ T cells (P=0.039) and release of IFN-γ (P=0.013) and TNF-α (P=0.045) after ex-vivo T cell stimulation of whole blood were significantly higher. Furthermore, the postoperative count of basophils was significantly lower (P=0.011), HLA-DR expressing CD8- T cells were tendentially lower (P=0.058) and more suppressed (P=0.035). The suppression of IFN-γ (P=0.003) and TNF-α (P=0.006) was significantly higher in these patients after ex-vivo T cell stimulation but absolute values were similar between the groups. IL-10 release of lipopolysaccharide-stimulated whole blood was tendentially more suppressed after perioperative hyperglycemia (P=0.084). CONCLUSIONS: Severe perioperative hyperglycemia attenuated postoperative basophil count, T cell activation and monocytic function. These patients were also at preoperative higher immune activation.


Assuntos
Basófilos , Hiperglicemia/sangue , Monócitos/fisiologia , Neoplasias/sangue , Neoplasias/cirurgia , Complicações Pós-Operatórias/sangue , Linfócitos T/fisiologia , Idoso , Glicemia/análise , Feminino , Humanos , Hiperglicemia/complicações , Contagem de Leucócitos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Período Perioperatório , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Índice de Gravidade de Doença
11.
Artigo em Alemão | MEDLINE | ID: mdl-28301890

RESUMO

A 42-year-old patient presented with acute allodynia and hyperalgesia in her distal limbs, most severe in the innervation area of the ulnar nerve. The patient developed critical illness myopathy/polyneuropathy after septic shock 5 months prior to her presentation. After exclusion of differential diagnosis, "late onset small fiber neuropathy" after critical illness was diagnosed. Recent studies showed small fiber lesions during critical illness and in follow-up exams, where additionally neuropathic pain were proved. Dysfunction of voltage-gated Sodium channels related to severe insulin resistance during critical illness might explain the pathophysiology, as seen in critical illness myopathy/polyneuropathy. Therefore we recommend cooling, pharmacotherapy with carbamazepin/oxcarbazepine, tricyclic antidepressive agents and peripheral nerve blocks to treat patients with "late onset small fiber neuropathy" after critical illness.


Assuntos
Polineuropatias/complicações , Sepse/complicações , Sepse/diagnóstico , Neuropatia de Pequenas Fibras/etiologia , Neuropatia de Pequenas Fibras/terapia , Adulto , Analgésicos não Entorpecentes/administração & dosagem , Anestésicos Locais/administração & dosagem , Antidepressivos Tricíclicos/administração & dosagem , Terapia Combinada/métodos , Estado Terminal , Feminino , Humanos , Hipotermia Induzida/métodos , Polineuropatias/diagnóstico , Polineuropatias/terapia , Sepse/terapia , Neuropatia de Pequenas Fibras/diagnóstico , Resultado do Tratamento
12.
Crit Care ; 21(1): 9, 2017 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-28065165

RESUMO

BACKGROUND: Intensive care unit (ICU)-acquired weakness in critically ill patients is a common and significant complication affecting the course of critical illness. Whole-body vibration is known to be effective muscle training and may be an option in diminishing weakness and muscle wasting. Especially, patients who are immobilized and not available for active physiotherapy may benefit. Until now whole-body vibration was not investigated in mechanically ventilated ICU patients. We investigated the safety, feasibility, and metabolic response of whole-body vibration in critically ill patients. METHODS: We investigated 19 mechanically ventilated, immobilized ICU patients. Passive range of motion was performed prior to whole-body vibration therapy held in the supine position for 15 minutes. Continuous monitoring of vital signs, hemodynamics, and energy metabolism, as well as intermittent blood sampling, took place from the start of baseline measurements up to 1 hour post intervention. We performed comparative longitudinal analysis of the phases before, during, and after intervention. RESULTS: Vital signs and hemodynamic parameters remained stable with only minor changes resulting from the intervention. No application had to be interrupted. We did not observe any adverse event. Whole-body vibration did not significantly and/or clinically change vital signs and hemodynamics. A significant increase in energy expenditure during whole-body vibration could be observed. CONCLUSIONS: In our study the application of whole-body vibration was safe and feasible. The technique leads to increased energy expenditure. This may offer the chance to treat patients in the ICU with whole-body vibration. Further investigations should focus on the efficacy of whole-body vibration in the prevention of ICU-acquired weakness. TRIAL REGISTRATION: Applicability and Safety of Vibration Therapy in Intensive Care Unit (ICU) Patients. ClinicalTrials.gov NCT01286610 . Registered 28 January 2011.


Assuntos
Debilidade Muscular/prevenção & controle , Vibração/uso terapêutico , Cuidados Críticos/métodos , Feminino , Hemodinâmica/fisiologia , Humanos , Imobilização/efeitos adversos , Imobilização/fisiologia , Unidades de Terapia Intensiva/organização & administração , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/terapia
13.
Crit Care Med ; 45(2): e169-e183, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27661566

RESUMO

OBJECTIVE: In sepsis, the disease course of critically ill patients is often complicated by muscle failure leading to ICU-acquired weakness. The myokine transforming growth factor-ß1 increases during inflammation and mediates muscle atrophy in vivo. We observed that the transforming growth factor-ß1 inhibitor, secreted frizzled-related protein 2, was down-regulated in skeletal muscle of ICU-acquired weakness patients. We hypothesized that secreted frizzled-related protein 2 reduction enhances transforming growth factor-ß1-mediated effects and investigated the interrelationship between transforming growth factor-ß1 and secreted frizzled-related protein 2 in inflammation-induced atrophy. DESIGN: Observational study and prospective animal trial. SETTING: Two ICUs and research laboratory. PATIENTS/SUBJECTS: Twenty-six critically ill patients with Sequential Organ Failure Assessment scores greater than or equal to 8 underwent a skeletal muscle biopsy from the vastus lateralis at median day 5 in ICU. Four patients undergoing elective orthopedic surgery served as controls. To search for signaling pathways enriched in muscle of ICU-acquired weakness patients, a gene set enrichment analysis of our recently published gene expression profiles was performed. Quantitative reverse transcriptase-polymerase chain reaction, Western blot, and immunohistochemistry were used to analyze secreted frizzled-related protein 2 expression and protein content. A mouse model of inflammation-induced skeletal muscle atrophy due to polymicrobial sepsis and cultured myocytes were used for mechanistic analyses. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Gene set enrichment analysis uncovered transforming growth factor-ß1 signaling activation in vastus lateralis from ICU-acquired weakness patients. Muscular secreted frizzled-related protein 2 expression was reduced after 5 days in ICU. Likewise, muscular secreted frizzled-related protein 2 expression was decreased early and continuously in mice with inflammation-induced atrophy. In muscle, secreted frizzled-related protein 2 was predominantly contained in fast twitch/type II myofibers. Secreted frizzled-related protein 2 physically interacted and colocalized with transforming growth factor-ß1 through its cysteine-rich domain. Finally, secreted frizzled-related protein 2 prevented transforming growth factor-ß1-induced atrophy in C2C12 myotubes. CONCLUSIONS: Muscular secreted frizzled-related protein 2 is down-regulated in ICU-acquired weakness patients and mice with inflammation-induced muscle atrophy. Decreased secreted frizzled-related protein 2 possibly establishes a positive feedback loop enhancing transforming growth factor-ß1-mediated atrophic effects in inflammation-induced atrophy.


Assuntos
Inflamação/complicações , Proteínas de Membrana/fisiologia , Atrofia Muscular/etiologia , Animais , Biópsia , Western Blotting , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Fibras Musculares Esqueléticas/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular/induzido quimicamente , Atrofia Muscular/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta1/fisiologia
14.
Ann Intensive Care ; 6(1): 70, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27439710

RESUMO

BACKGROUND: Continuous glucose monitoring (CGM) has not yet been implemented in the intensive care unit (ICU) setting. The purpose of this study was to evaluate reliability, feasibility, nurse acceptance and accuracy of the Medtronic Sentrino(®) CGM system in critically ill patients. METHODS: Sensors were inserted into the subcutaneous tissue of the patient's thigh, quantifying interstitial glucose concentration for up to 72 h per sensor. Reliability and feasibility analysis included frequency of data display, data gaps and reasons for sensor removal. We surveyed nurse acceptance in a questionnaire. For the accuracy analysis, we compared sensor values to glucose values obtained via blood gas analysis. Potential benefits of CGM were investigated in intra-individual analyses of factors, such as glycemic variability or time in target range achieved with CGM compared to that achieved with intermittent glucose monitoring. RESULTS: The device generated 68,655 real-time values from 31 sensors in 20 critically ill patients. 532 comparative blood glucose values were collected. Data were displayed during 32.5 h [16.0/62.4] per sensor, which is 45.1 % of the expected time of 72 h and 84.8 % of 37.9 h actual monitoring time. 21 out of 31 sensors were removed prematurely. 79.1 % of the nursing staff rated the device as not beneficial; the response rate was one-third. Mean absolute relative difference was 15.3 % (CI 13.5-17.0 %). Clarke error grid: 76.9 % zone A, 21.6 % zone B, 0.2 % zone C, 0.9 % zone D, 0.4 % zone E. Bland-Altman plot: mean bias +0.53 mg/dl, limits of agreement +64.6 and -63.5 mg/dl. Accuracy deteriorated during elevated glycemic variability and in the hyperglycemic range. There was no reduction in dysglycemic events during CGM compared to 72 h before and after CGM. If CGM was measuring accurately, it identified more hyperglycemic events when compared to intermittent measurements. This study was not designed to evaluate potential benefits of CGM on glucose control. CONCLUSIONS: The subcutaneous CGM system did not perform with satisfactory accuracy, feasibility, or nursing acceptance when evaluated in 20 medical-surgical ICU patients. Low point accuracy and prolonged data gaps significantly limited the potential clinical usefulness of the CGM trend data. Accurate continuous data display, with a MARD < 14 %, showed potential benefits in a subgroup of our patients. Trial registration NCT02296372; Ethic vote Charité EA2/095/14.

16.
Crit Care ; 18(5): 545, 2014 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-25263070

RESUMO

INTRODUCTION: ICU-acquired weakness (ICUAW) complicates the disease course of critically ill patients. Inflammation and acute-phase response occur directly within myocytes and contribute to ICUAW. We observed that tripartite motif-containing 62 (TRIM62), an E3 ubiquitin ligase and modifier of inflammation, is increased in the skeletal muscle of ICUAW patients. We investigated the regulation and function of muscular TRIM62 in critical illness. METHODS: Twenty-six critically ill patients with Sequential Organ Failure Assessment scores ≥8 underwent two skeletal muscle biopsies from the vastus lateralis at median days 5 and 15 in the ICU. Four patients undergoing elective orthopedic surgery served as controls. TRIM62 expression and protein content were analyzed in these biopsies. The kinetics of Trim62, Atrogin1 and MuRF1 expression were determined in the gastrocnemius/plantaris and tibialis anterior muscles from mouse models of inflammation-, denervation- and starvation-induced muscle atrophy to differentiate between these contributors to ICUAW. Cultured myocytes were used for mechanistic analyses. RESULTS: TRIM62 expression and protein content were increased early and remained elevated in muscles from critically ill patients. In all three animal models, muscular Trim62 expression was early and continuously increased. Trim62 was expressed in myocytes, and its overexpression activated the atrophy-inducing activator protein 1 signal transduction pathway. Knockdown of Trim62 by small interfering RNA inhibited lipopolysaccharide-induced interleukin 6 expression. CONCLUSIONS: TRIM62 is activated in the muscles of critically ill patients. It could play a role in the pathogenesis of ICUAW by activating and maintaining inflammation in myocytes. TRIAL REGISTRATION: Current Controlled Trials ID: ISRCTN77569430 (registered 13 February 2008).


Assuntos
Inflamação , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adulto , Idoso , Animais , Estado Terminal/terapia , Modelos Animais de Doenças , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases/genética
17.
PLoS One ; 9(3): e92048, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24651840

RESUMO

OBJECTIVES: Systemic inflammation is a major risk factor for critical-illness myopathy (CIM) but its pathogenic role in muscle is uncertain. We observed that interleukin 6 (IL-6) and serum amyloid A1 (SAA1) expression was upregulated in muscle of critically ill patients. To test the relevance of these responses we assessed inflammation and acute-phase response at early and late time points in muscle of patients at risk for CIM. DESIGN: Prospective observational clinical study and prospective animal trial. SETTING: Two intensive care units (ICU) and research laboratory. PATIENTS/SUBJECTS: 33 patients with Sequential Organ Failure Assessment scores ≥ 8 on 3 consecutive days within 5 days in ICU were investigated. A subgroup analysis of 12 patients with, and 18 patients without CIM (non-CIM) was performed. Two consecutive biopsies from vastus lateralis were obtained at median days 5 and 15, early and late time points. Controls were 5 healthy subjects undergoing elective orthopedic surgery. A septic mouse model and cultured myoblasts were used for mechanistic analyses. MEASUREMENTS AND MAIN RESULTS: Early SAA1 expression was significantly higher in skeletal muscle of CIM compared to non-CIM patients. Immunohistochemistry showed SAA1 accumulations in muscle of CIM patients at the early time point, which resolved later. SAA1 expression was induced by IL-6 and tumor necrosis factor-alpha in human and mouse myocytes in vitro. Inflammation-induced muscular SAA1 accumulation was reproduced in a sepsis mouse model. CONCLUSIONS: Skeletal muscle contributes to general inflammation and acute-phase response in CIM patients. Muscular SAA1 could be important for CIM pathogenesis. TRIAL REGISTRATION: ISRCTN77569430.


Assuntos
Reação de Fase Aguda/imunologia , Inflamação/complicações , Inflamação/patologia , Músculo Esquelético/patologia , Doenças Musculares/complicações , Doenças Musculares/patologia , Reação de Fase Aguda/patologia , Adulto , Animais , Estudos de Casos e Controles , Estado Terminal , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/sangue , Inflamação/genética , Mediadores da Inflamação/metabolismo , Interleucina-6/sangue , Lipopolissacarídeos/farmacologia , Masculino , Membranas/efeitos dos fármacos , Camundongos , Pessoa de Meia-Idade , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/imunologia , Doenças Musculares/sangue , Doenças Musculares/genética , Análise de Sequência com Séries de Oligonucleotídeos , Sepse/complicações , Sepse/patologia , Proteína Amiloide A Sérica/metabolismo , Fator de Necrose Tumoral alfa/sangue
18.
Intensive Care Med ; 40(4): 528-38, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24531339

RESUMO

IMPORTANCE: Intensive care unit (ICU)-acquired muscle wasting is a devastating complication leading to persistent weakness and functional disability. The mechanisms of this myopathy are unclear, but a disturbed balance of myosin heavy chain (MyHC) is implicated. OBJECTIVE: To investigate pathways of myosin turnover in severe critically ill patients at high risk of ICU-acquired weakness. DESIGN: Prospective, mechanistic, observational study. SETTING: Interdisciplinary ICUs of a university hospital. PARTICIPANTS: Twenty-nine patients with Sequential Organ Failure Assessment (SOFA) scores of at least 8 on three consecutive days within the first 5 days in ICU underwent two consecutive open skeletal muscle biopsies from the vastus lateralis at median days 5 and 15. Control biopsy specimens were from healthy subjects undergoing hip-replacement surgery. INTERVENTIONS: None. MAIN OUTCOME(S) AND MEASURE(S): Time-dependent changes in myofiber architecture, MyHC synthesis, and degradation were determined and correlated with clinical data. RESULTS: ICU-acquired muscle wasting was characterized by early, disrupted myofiber ultrastructure followed by atrophy of slow- and fast-twitch myofibers at later time points. A rapid decrease in MyHC mRNA and protein expression occurred by day 5 and persisted at day 15 (P < 0.05). Expression of the atrophy genes MuRF-1 and Atrogin1 was increased at day 5 (P < 0.05). Early MuRF-1 protein content was closely associated with late myofiber atrophy and the severity of weakness. CONCLUSIONS AND RELEVANCE: Decreased synthesis and increased degradation of MyHCs contribute to ICU-acquired muscle wasting. The rates and time frames suggest that pathogenesis of muscle failure is initiated very early during critical illness. The persisting reduction of MyHC suggests that sustained treatment is required.


Assuntos
Cuidados Críticos , Estado Terminal/terapia , Debilidade Muscular/metabolismo , Miosinas/metabolismo , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/patologia , Estudos Prospectivos
19.
Muscle Nerve ; 50(3): 431-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24415656

RESUMO

INTRODUCTION: Muscle weakness in critically ill patients after discharge varies. It is not known whether the electrophysiological distinction between critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) during the early part of a patient's stay in the intensive care unit (ICU) predicts long-term prognosis. METHODS: This was a prospective cohort study of mechanically ventilated ICU patients undergoing conventional nerve conduction studies and direct muscle stimulation in addition to neurological examination during their ICU stay and 1 year after ICU discharge. RESULTS: Twenty-six patients (7 ICU controls, 8 CIM patients, and 11 CIM/CIP patients) were evaluated 1 year after discharge from the ICU. Eighty-eight percent (n = 7) of CIM patients recovered within 1 year compared with 55% (n = 6) of CIM/CIP patients. Thirty-six percent (n = 4) of CIM/CIP patients still needed assistance during their daily routine (P = 0.005). CONCLUSIONS: Early electrophysiological testing predicts long-term outcome in ICU survivors. CIM has a significantly better prognosis than CIM/CIP.


Assuntos
Estado Terminal/terapia , Doenças Musculares/terapia , Polineuropatias/terapia , Potenciais de Ação/fisiologia , Adolescente , Adulto , Idoso , Eletrodiagnóstico , Eletrofisiologia , Feminino , Seguimentos , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/fisiopatologia , Contração Muscular/fisiologia , Força Muscular/fisiologia , Músculo Esquelético/fisiopatologia , Condução Nervosa , Exame Neurológico , Recuperação de Função Fisiológica , Sepse/complicações , Resultado do Tratamento , Adulto Jovem
20.
J Transl Med ; 11: 157, 2013 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-23806032

RESUMO

BACKGROUND: 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children. METHODS: The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. PROSPECT: The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01370044.


Assuntos
Dióxido de Carbono/uso terapêutico , Convulsões Febris/terapia , Pré-Escolar , Método Duplo-Cego , Desenho de Equipamento , Humanos , Lactente , Estudos Prospectivos , Qualidade de Vida , Projetos de Pesquisa , Pesquisa Médica Translacional , Resultado do Tratamento
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