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2.
Pneumologie ; 2023 Oct 13.
Artigo em Alemão | MEDLINE | ID: mdl-37832578

RESUMO

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

4.
Circulation ; 146(18): 1357-1366, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36168956

RESUMO

BACKGROUND: This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia. METHODS: An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome. RESULTS: A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79-1.40]; P=0.822). In-hospital mortality was 62.5% (75 of 120) in the hypothermic temperature control as compared with 57.6% (68 of 118) in the normothermia group (relative risk, 1.11 [95% CI, 0.86-1.46, P=0.443). Favorable functional outcome (Cerebral Performance Category 1 or 2) by day 180 was 22.5% (27 of 120) in the hypothermic temperature control, compared with 23.7% (28 of 118) in the normothermia group (relative risk, 1.04 [95% CI, 0.78-1.44]; P=0.822). The study was prematurely terminated because of futility. CONCLUSIONS: Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT00457431.


Assuntos
Reanimação Cardiopulmonar , Hipotermia Induzida , Parada Cardíaca Extra-Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Hipotermia Induzida/efeitos adversos , Temperatura , Coma , Hospitais , Resultado do Tratamento
5.
Angiogenesis ; 25(4): 503-515, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35723762

RESUMO

AIMS: Although coronavirus disease 2019 (COVID-19) and bacterial sepsis are distinct conditions, both are known to trigger endothelial dysfunction with corresponding microcirculatory impairment. The purpose of this study was to compare microvascular injury patterns and proteomic signatures in COVID-19 and bacterial sepsis patients. METHODS AND RESULTS: This multi-center, observational study included 22 hospitalized adult COVID-19 patients, 43 hospitalized bacterial sepsis patients, and 10 healthy controls from 4 hospitals. Microcirculation and glycocalyx dimensions were quantified via intravital sublingual microscopy. Plasma proteins were measured using targeted proteomics (Olink). Coregulation and cluster analysis of plasma proteins was performed using a training-set and confirmed in a test-set. An independent external cohort of 219 COVID-19 patients was used for validation and outcome analysis. Microcirculation and plasma proteome analysis found substantial overlap between COVID-19 and bacterial sepsis. Severity, but not disease entity explained most data variation. Unsupervised correlation analysis identified two main coregulated plasma protein signatures in both diseases that strictly counteract each other. They were associated with microvascular dysfunction and several established markers of clinical severity. The signatures were used to derive new composite biomarkers of microvascular injury that allow to predict 28-day mortality or/and intubation (area under the curve 0.90, p < 0.0001) in COVID-19. CONCLUSION: Our data imply a common biological host response of microvascular injury in both bacterial sepsis and COVID-19. A distinct plasma signature correlates with endothelial health and improved outcomes, while a counteracting response is associated with glycocalyx breakdown and high mortality. Microvascular health biomarkers are powerful predictors of clinical outcomes.


Assuntos
COVID-19 , Sepse , Adulto , Biomarcadores/metabolismo , Humanos , Microcirculação , Proteoma , Proteômica
6.
Crit Care ; 26(1): 190, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35765102

RESUMO

BACKGROUND: Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. METHODS: 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. RESULTS: Most patients were between 50 and 70 years of age. PaO2/FiO2 ratio prior to ECMO was 72 mmHg (IQR: 58-99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41-0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28-1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. CONCLUSIONS: Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. TRIAL REGISTRATION: Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 .


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório , COVID-19/terapia , Humanos , Unidades de Terapia Intensiva , Pandemias , Síndrome do Desconforto Respiratório/terapia , Análise de Sobrevida
7.
Dtsch Med Wochenschr ; 147(6): 319-325, 2022 03.
Artigo em Alemão | MEDLINE | ID: mdl-35291037

RESUMO

MONITORING OF ANALGESIA, SEDATION AND DELIRIUM: The prerequisite for monitoring goal-oriented analgesia and screening for the presence of delirium is the use of validated measuring instruments such as the Richmond Agitation and Sedation Scale as well as an adequate medical and intensive care staffing ratio. IMPLEMENTATION OF ANALGESIA AND SEDATION: The goal, if possible, is an awake, oriented, cooperative patient who is free of pain. In this regard, multimodal analgesic treatment is of great importance. The lowest possible sedation should also be aimed for in COVID-19 patients, although deep sedation is recommended for invasively ventilated COVID-19 patients in the prone position.


Assuntos
Analgesia , COVID-19 , Delírio , COVID-19/terapia , Delírio/terapia , Humanos , Dor , Manejo da Dor
8.
Intensive Care Med ; 48(3): 332-342, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35146534

RESUMO

PURPOSE: The question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors. METHODS: 297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted. RESULTS: Patients had a median age of 56 (IQR 44-65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1-32.4%). Low platelet count (HR 0.997, 95% CI 0.996-0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012-1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081-3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044-2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO. CONCLUSION: The overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.


Assuntos
Oxigenação por Membrana Extracorpórea , Neoplasias , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Adulto , Idoso , Oxigenação por Membrana Extracorpórea/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/terapia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos
9.
J Clin Med ; 10(22)2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34830721

RESUMO

Extracorporeal membrane oxygenation (ECMO) represents a viable therapy option for patients with refractory acute respiratory distress syndrome (ARDS). Currently, veno-venous (vv) ECMO is frequently used in patients suffering from coronavirus disease 2019 (COVID-19). VV-ECMO was also frequently utilised during the influenza pandemic and experience with this complex and invasive treatment has increased worldwide since. However, data on comparison of clinical characteristics and outcome of patients with COVID-19 and influenza-related severe ARDS treated with vv-ECMO are scarce. This is a retrospective analysis of all consecutive patients treated with vv/(veno-arterial)va-ECMO between January 2009 and January 2021 at the University Medical Centre Hamburg-Eppendorf in Germany. All patients with confirmed COVID-19 or influenza were included. Patient characteristics, parameters related to ICU and vv/va-ECMO as well as clinical outcomes were compared. Mortality was assessed up to 90 days after vv/va-ECMO initiation. Overall, 113 patients were included, 52 (46%) with COVID-19 and 61 (54%) with influenza-related ARDS. Median age of patients with COVID-19 and influenza was 58 (IQR 53-64) and 52 (39-58) years (p < 0.001), 35% and 31% (p = 0.695) were female, respectively. Charlson Comorbidity Index was 3 (1-5) and 2 (0-5) points in the two groups (p = 0.309). Median SAPS II score pre-ECMO was 27 (24-36) vs. 32 (28-41) points (p = 0.009), and SOFA score was 13 (11-14) vs. 12 (8-15) points (p = 0.853), respectively. Median P/F ratio pre-ECMO was 64 (46-78) and 73 (56-104) (p = 0.089); pH was 7.20 (7.16-7.29) and 7.26 (7.18-7.33) (p = 0.166). Median days on vv/va-ECMO were 17 (7-27) and 11 (7-20) (p = 0.295), respectively. Seventy-one percent and sixty-nine percent had renal replacement therapy (p = 0.790). Ninety-four percent of patients with COVID-19 and seventy-seven percent with influenza experienced vv/va-ECMO-associated bleeding events (p = 0.004). Thirty-four percent and fifty-five percent were successfully weaned from ECMO (p = 0.025). Ninety-day mortality was 65% and 57% in patients with COVID-19 and influenza, respectively (p = 0.156). Median length of ICU stay was 24 (13-44) and 28 (16-14) days (p = 0.470), respectively. Despite similar disease severity, the use of vv/va-ECMO in ARDS related to COVID-19 and influenza resulted in similar outcomes at 90 days. A significant higher rate of bleeding complications and thrombosis was observed in patients with COVID-19.

10.
J Crit Care ; 62: 12-18, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33227591

RESUMO

PURPOSE: Whether therapeutic hypothermia (TH) adds to the risk of bleeding in patients on extracorporeal life support (ECLS) peri-cardiac arrest remains unknown. MATERIAL AND METHODS: Single center retrospective study on patients receiving veno-arterial ECLS peri-cardiac arrest ± TH at 32-34 °C (January 2009-December 2015). PRIMARY OUTCOME: major bleeding (including intracerebral hemorrhage, ICH) < 72 h of cardiac arrest. Logistic regression and marginal structural models were used to analyze associations with major bleeding. RESULTS: Of 66 patients receiving ECLS, 36 were treated with TH. Major bleeding occurred in 14 patients (39%) treated with ECLS+TH and in 17 patients (57%) with ECLS alone. ICH was reported in 3 (8%) and one patient (3%), respectively. There was no difference in mortality, but lung injury occurred more often in ECLS+TH. A platelet count <60 × 109/L but not TH was associated with major bleeding (including ICH). The estimated causal risk ratio of TH on the occurrence of major bleeding (including ICH) at 72 h post cardiac arrest was 0.95 (95%CI 0.62-1.45). CONCLUSIONS: Bleeding complications were common in our study. However, TH (32-34 °C) was not associated with an increased risk of major bleeding in patients on ECLS peri-cardiac arrest.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Hipotermia Induzida , Adulto , Oxigenação por Membrana Extracorpórea/efeitos adversos , Parada Cardíaca/terapia , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Hipotermia Induzida/efeitos adversos , Estudos Retrospectivos
11.
Angiogenesis ; 24(1): 145-157, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33058027

RESUMO

RATIONALE: Pre-clinical and autopsy studies have fueled the hypothesis that a dysregulated vascular endothelium might play a central role in the pathogenesis of ARDS and multi-organ failure in COVID-19. OBJECTIVES: To comprehensively characterize and quantify microvascular alterations in patients with COVID-19. METHODS: Hospitalized adult patients with moderate-to-severe or critical COVID-19 (n = 23) were enrolled non-consecutively in this prospective, observational, cross-sectional, multi-center study. Fifteen healthy volunteers served as controls. All participants underwent intravital microscopy by sidestream dark field imaging to quantify vascular density, red blood cell velocity (VRBC), and glycocalyx dimensions (perfused boundary region, PBR) in sublingual microvessels. Circulating levels of endothelial and glycocalyx-associated markers were measured by multiplex proximity extension assay and enzyme-linked immunosorbent assay. MEASUREMENTS AND MAIN RESULTS: COVID-19 patients showed an up to 90% reduction in vascular density, almost exclusively limited to small capillaries (diameter 4-6 µm), and also significant reductions of VRBC. Especially, patients on mechanical ventilation showed severe glycocalyx damage as indicated by higher PBR values (i.e., thinner glycocalyx) and increased blood levels of shed glycocalyx constituents. Several markers of endothelial dysfunction were increased and correlated with disease severity in COVID-19. PBR (AUC 0.75, p = 0.01), ADAMTS13 (von Willebrand factor-cleaving protease; AUC 0.74, p = 0.02), and vascular endothelial growth factor A (VEGF-A; AUC 0.73, p = 0.04) showed the best discriminatory ability to predict 60-day in-hospital mortality. CONCLUSIONS: Our data clearly show severe alterations of the microcirculation and the endothelial glycocalyx in patients with COVID-19. Future therapeutic approaches should consider the importance of systemic vascular involvement in COVID-19.


Assuntos
COVID-19/fisiopatologia , Endotélio Vascular/fisiopatologia , Microcirculação , Idoso , Área Sob a Curva , Estudos Transversais , Feminino , Seguimentos , Glicocálix/química , Voluntários Saudáveis , Humanos , Inflamação , Microscopia Intravital , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Perfusão , Estudos Prospectivos , Resultado do Tratamento
12.
Ann Intensive Care ; 10(1): 161, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259044

RESUMO

BACKGROUND: There is scarce evidence on the feasibility, safety and resource utilisation of active mobilisation in critically ill patients on extracorporeal life support (ECLS). METHODS: This prospective observational single-centre study included all consecutive critically ill patients on ECLS admitted to an academic centre in Germany over a time period of one year. The level of mobilisation was categorised according to the ICU Mobility Scale (IMS). Primary outcome was complications during mobilisation. RESULTS: During the study period, active mobilisation with an activity level on the IMS of ≥ 3 was performed at least on one occasion in 43 out of 115 patients (37.4%). A total of 332 mobilisations with IMS ≥ 3 were performed during 1242 ECLS days (26.7%). ECLS configurations applied were va-ECMO (n = 63), vv-ECMO (n = 26), vv-ECCO2R (n = 12), av-ECCO2R (n = 10), and RVAD (n = 4). Femoral cannulation had been in place in 108 patients (93.9%). The median duration of all mobilisation activities with IMS ≥ 3 was 130 min (IQR 44-215). All mobilisations were undertaken by a multi-professional ECLS team with a median number of 3 team members involved (IQR 3-4). Bleeding from cannulation site requiring transfusion and/or surgery occurred in 6.9% of actively mobilised patients and in 15.3% of non-mobilised patients. During one mobilisation episode, accidental femoral cannula displacement occurred with immediate and effective recannulation. Sedation was the major reason for non-mobilisation. CONCLUSIONS: Active mobilisation (IMS ≥ 3) of ECLS patients undertaken by an experienced multi-professional team was feasible, and complications were infrequent and managed successfully. Larger prospective multicentre studies are needed to further evaluate early goal directed sedation and mobilisation bundles in patients on ECLS.

13.
Dtsch Med Wochenschr ; 144(23): 1611-1618, 2019 11.
Artigo em Alemão | MEDLINE | ID: mdl-31752033

RESUMO

A delirium in patients in the intensive care unit (ICU) is a manifestation of a severe acute dysfunction of the brain. It has a high prevalence and is associated with a relevant increase in morbidity and mortality. A cholinergic deficit and dopaminergic overactivity are considered to be a cause of delirium. Polypharmacy, which is often present before admission to the ICU, especially in the elderly, plays a key role as a trigger. The knowledge and identification of risk factors for delirium is a precondition for the early and effective prevention of delirium. The aim is the pre-operative or pre-interventional optimization of modifiable risk factors. Early and effective prevention of delirium can improve clinical outcome, reduce mortality, and positively impact long-term functional outcome. Non-pharmacological measures are always the basis for the prevention of delirium: maintenance of the day-night rhythm, sleep promotion at night and stimulation during the day, involvement of relatives, the avoidance of dehydration and malnutrition, and others more. They are pharmacologically accompanied by an effective analgesia and a target and symptom-oriented sedation with well controllable, as little as possible delirogenic substances. Interdisciplinary and interprofessional cooperation is essential so that preventive concepts significantly reduce the risk of delirium, even in high-risk patients.


Assuntos
Delírio , Unidades de Terapia Intensiva , Idoso , Delírio/diagnóstico , Delírio/etiologia , Delírio/prevenção & controle , Delírio/terapia , Humanos , Fatores de Risco
14.
Int J Artif Organs ; 42(2): 57-64, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30545255

RESUMO

OBJECTIVES:: The aim of this study is to describe the in vitro adsorption of anti-infective drugs onto an extracorporeal cytokine adsorber. METHODS:: Various anti-infective drugs (ß-lactams, quinolones, aminoglycosides, glycopeptides, azole antimycotics) were prepared in normal saline 0.9% and human albumin 5%, and pumped through a cytokine cartridge (CytoSorb®; CytoSorbents Corporation, Monmouth Junction, NJ, USA) at a flow rate of 1.2 L/h for 1.5 h. In addition, meropenem and ciprofloxacin were dissolved in reconstituted blood and run through a CytoSorb cartridge, which was integrated into a continuous renal replacement therapy circuit with a flow rate of 2 L/h for 18 h. Samples from the solution, pre- and post-filter, were quantified by high-performance liquid chromatography with ultraviolet detection and fluorescence polarisation immunoassay. RESULTS:: Observed mean clearance of the drugs in normal saline was 1.22 ± 0.07 L/h. In human albumin, clearance was 1.29 ± 0.08 L/h. In reconstituted blood, clearance of meropenem decreased from 5.4 to 1.4 L/h and for ciprofloxacin from 6.3 to 4.3 L/h within the first 1.5 h because of early drug adsorption. Continuous renal replacement therapy clearance measured without CytoSorb was stable at 2 and 1.7 L/h, respectively. Approximately 400 mg of meropenem and 300 mg of ciprofloxacin had been adsorbed by CytoSorb, suggesting that these amounts are the maximum adsorptive capacity for these drugs. CONCLUSION:: In these settings, all tested drugs were adsorbed by the cartridge in relevant amounts. The identified maximum adsorptive capacity and the rapid decline in concentration during the first 1.5 h of CytoSorb use suggest that the administration of an additional dose within the first hours of CytoSorb treatment may be reasonable. In addition, early therapeutic drug monitoring should be considered.


Assuntos
Adsorção , Albuminas/química , Anti-Infecciosos/isolamento & purificação , Citocinas/isolamento & purificação , Plasma/química , Solução Salina/química , Humanos , Técnicas In Vitro , Polímeros
15.
Crit Care ; 22(1): 25, 2018 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-29382394

RESUMO

BACKGROUND: The aim of the study was to describe the population pharmacokinetics (PK) of meropenem in critically ill patients receiving sustained low-efficiency dialysis (SLED). METHODS: Prospective population PK study on 19 septic patients treated with meropenem and receiving SLED for acute kidney injury. Serial blood samples for determination of meropenem concentrations were taken before, during and after SLED in up to three sessions per patient. Nonparametric population PK analysis with Monte Carlo simulations were used. Pharmacodynamic (PD) targets of 40% and 100% time above the minimal inhibitory concentration (f T > MIC) were used for probability of target attainment (PTA) and fractional target attainment (FTA) against Pseudomonas aeruginosa. RESULTS: A two-compartment linear population PK model was most appropriate with residual diuresis supported as significant covariate affecting meropenem clearance. In patients without residual diuresis the PTA for both targets (40% and 100% f T > MIC) and susceptible P. aeruginosa (MIC ≤ 2 mg/L) was > 95% for a dose of 0.5 g 8-hourly. In patients with a residual diuresis of 300 mL/d 1 g 12-hourly and 2 g 8-hourly would be required to achieve a PTA of > 95% and 93% for targets of 40% f T > MIC and 100% f T > MIC, respectively. A dose of 2 g 8-hourly would be able to achieve a FTA of 97% for 100% f T > MIC in patients with residual diuresis. CONCLUSIONS: We found a relevant PK variability for meropenem in patients on SLED, which was significantly influenced by the degree of residual diuresis. As a result dosing recommendations for meropenem in patients on SLED to achieve adequate PD targets greatly vary. Therapeutic drug monitoring may help to further optimise individual dosing. TRIAL REGISTRATION: Clincialtrials.gov, NCT02287493 .


Assuntos
Diálise/métodos , Sepse/tratamento farmacológico , Tienamicinas/farmacocinética , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controle , Adulto , Idoso , Estado Terminal/reabilitação , Feminino , Alemanha , Humanos , Masculino , Meropeném , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Método de Monte Carlo , Escores de Disfunção Orgânica , Estudos Prospectivos , Tienamicinas/uso terapêutico
17.
J Antimicrob Chemother ; 72(5): 1433-1440, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28175308

RESUMO

Objectives: To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED). Patients and methods: This study was performed in ICUs of a university hospital. We collected blood samples during three consecutive days of SLED sessions in patients receiving ceftazidime. Concentration versus time curves were analysed using a population PKs approach with Pmetrics ® . Monte Carlo simulation for the first 24 h including a 6 h SLED session was performed with the final model. The fractional target attainment against the MIC of Pseudomonas aeruginosa was executed using targets of 50 and 100% fT > MIC . Results: In total, 211 blood samples of 16 critically ill patients under SLED were collected. SLED treatments were 299.3 (68.4) min in duration. A two-compartment linear population PK model was most appropriate. The mean (SD) CL of ceftazidime on SLED, and off SLED were 5.32 (3.2), 1.06 (1.0) L/h respectively. The PTA for 50% fT > MIC for a dose of 1 g intravenously every 8 h was 98%. Assuming a target of 100% fT > MIC a dose of 2 g every 12 h covers isolates with MIC ≤8 mg/L with a PTA of 96%. Conclusion: In critically ill patients receiving SLED, ceftazidime 1 g every 8 h and ceftazidime 2 g every 12 h appear to be sufficient for achieving traditional (50% fT > MIC ) and aggressive PD targets (100% fT > MIC ) for susceptible isolates (MIC ≤8 mg/L), respectively.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Ceftazidima/farmacocinética , Simulação por Computador , Diálise Renal , Idoso , Antibacterianos/sangue , Antibacterianos/farmacologia , Ceftazidima/administração & dosagem , Ceftazidima/sangue , Ceftazidima/farmacologia , Estado Terminal , Feminino , Hospitais Universitários , Humanos , Unidades de Terapia Intensiva , Cinética , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Método de Monte Carlo , Pseudomonas aeruginosa/efeitos dos fármacos , Sepse/complicações , Sepse/tratamento farmacológico
19.
Dtsch Med Wochenschr ; 142(2): 102-109, 2017 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-28114715

RESUMO

The clinical course of moderate to severe ARDS often leads to prolonged weaning. Prolonged weaning utilizes considerable resources in intensive care medicine and is associated with a high mortality. The pathophysiology of prolonged weaning is complex and its understanding mandatory for its successful management. This article discusses and summarizes the most important causes of prolonged weaning and the corresponding treatment strategies to liberate patients with ARDS from the ventilator.


Assuntos
Pneumonia Associada à Ventilação Mecânica/mortalidade , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Síndrome do Desconforto Respiratório/mortalidade , Síndrome do Desconforto Respiratório/terapia , Desmame do Respirador/mortalidade , Desmame do Respirador/métodos , Medicina Baseada em Evidências , Humanos , Incidência , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
20.
Dtsch Med Wochenschr ; 141(24): 1758-1762, 2016 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-27903026

RESUMO

In acute exacerbations of COPD with acute hypercapnic respiratory failure and a pH 7.25 - 7.35, the initiation of non-invasive ventilation is the gold standard. However, absolute and relative contraindications have to be taken into account. The implementation of non-invasive ventilation in case of a severe respiratory acidosis necessitates a skilled therapeutic team and a close monitoring in order to avoid or perceive a NIV failure in time. In this case, the intubation and invasive mechanical ventilation is recommended. Ventilator settings have to aim at the prevention of an overinflation and increase of intrinsic PEEP. If severe hypercapnia and respiratory acidosis cannot be managed by mechanical ventilation, extracorporeal CO2 removal (ECCO2R) is a new treatment option. There are some reports about its use in awake patients in order to avoid an intubation. However, its general and primary use without optimizing medical therapy and mechanical ventilation is not indicated. ECCO2R is an experimental therapy in COPD with acute hypercapnic respiratory failure, its significance is still ambiguous. Therefore, it should only be applied in individual situations by a specialist team trained in its use.


Assuntos
Circulação Extracorpórea/métodos , Hipercapnia/etiologia , Hipercapnia/terapia , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Remoção de Componentes Sanguíneos/métodos , Dióxido de Carbono/sangue , Dióxido de Carbono/isolamento & purificação , Terapia Combinada/métodos , Progressão da Doença , Humanos , Hipercapnia/diagnóstico , Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória/diagnóstico , Resultado do Tratamento
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