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1.
J Pathol ; 2021 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-33586189

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to spread globally despite the worldwide implementation of preventive measures to combat the disease. Although most COVID-19 cases are characterised by a mild, self-limiting disease course, a considerable subset of patients develop a more severe condition, varying from pneumonia and acute respiratory distress syndrome (ARDS) to multi-organ failure (MOF). Progression of COVID-19 is thought to occur as a result of a complex interplay between multiple pathophysiological mechanisms, all of which may orchestrate SARS-CoV-2 infection and contribute to organ-specific tissue damage. In this respect, dissecting currently available knowledge of COVID-19 immunopathogenesis is crucially important, not only to improve our understanding of its pathophysiology, but also to fuel the rationale of both novel and repurposed treatment modalities. Various immune-mediated pathways during SARS-CoV-2 infection are relevant in this context, which relate to innate immunity, adaptive immunity, and autoimmunity. Pathological findings in tissue specimens of patients with COVID-19 provide valuable information with regard to our understanding of pathophysiology as well as the development of evidence-based treatment regimens. This review provides an updated overview of the main pathological changes observed in COVID-19 within the most commonly affected organ systems, with special emphasis on immunopathology. Current management strategies for COVID-19 include supportive care and the use of repurposed or symptomatic drugs, such as dexamethasone, remdesivir, and anticoagulants. Ultimately, prevention is key to combat COVID-19 and this requires appropriate measures to attenuate its spread and, above all, the development and implementation of effective vaccines. This article is protected by copyright. All rights reserved.

2.
Crit Care Med ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33591006

RESUMO

OBJECTIVES: To determine the safety and efficacy of human chorionic gonadotropin hormone-derivative EA-230 in cardiac surgery patients. Cardiac surgery induces systemic inflammation and may impair renal function, affecting patient outcome. EA-230 exerted immunomodulatory and renoprotective effects in preclinical models and was safe and showed efficacy in phase I and II human studies. DESIGN: Double-blinded, placebo-controlled, randomized study. SETTING: Collaboration of the Cardiothoracic Surgery, Anesthesiology, and the Intensive Care departments of a tertiary hospital in the Netherlands. PATIENTS: One hundred eighty patients undergoing an on-pump coronary artery bypass procedure with or without concomitant valve surgery. INTERVENTIONS: Ninety mg/kg/hr EA-230 or placebo administered during surgery. MEASUREMENTS AND MAIN RESULTS: During the study, no safety concerns emerged. EA-230 did not modulate interleukin-6 plasma concentrations (area under the curve 2,730 pg/mL × hr [1,968-3,760] vs 2,680 pg/mL × hr [2,090-3,570] for EA-230 and placebo group, respectively; p = 0.80). Glomerular filtration rate increased following surgery (mean ± SEM increase in the EA-230 vs placebo groups: glomerular filtration rateiohexol measured using iohexol plasma clearance: 19 ± 2 vs 16 ± 2 mL/min/1.73 m2; p = 0.13 and estimated glomerular filtration rate with the Modification of Diet in Renal Disease equation using creatinine: 6 ± 1 vs 2 ± 1 mL/min/1.73 m2; p = 0.01). The "injury" stage of the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria for acute kidney injury was 7% in the EA-230 group versus 18% in the placebo group (p = 0.07). In addition, EA-230-treated patients had a less positive fluid balance compared with placebo-treated patients (217 ± 108 vs 605 ± 103 mL; p = 0.01), while the use of vasoactive agents was similar in both groups (p = 0.39). Finally, hospital length of stay was shorter in EA-230 treated patients (8 d [7-11] vs 10 d [8-12]; p = 0.001). Efficacy results were more pronounced in patients that had longer duration of surgery and thus longer duration of study drug infusion. CONCLUSIONS: EA-230 was safe in patients undergoing on-pump cardiac surgery. It did not modulate interleukin-6 plasma concentrations but appeared to exert beneficial renal and cardiovascular effects and shortened in-hospital length of stay.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33526001

RESUMO

RATIONALE: Comprehensive studies addressing the incidence of physical, mental, and cognitive problems after ICU admission are lacking. With an increasing number of ICU survivors, an improved understanding of post-ICU problems is necessary. OBJECTIVES: To determine the occurrence and co-occurrence of new physical, mental, and cognitive problems among ICU survivors one year after ICU admission, their impact on daily functioning and risk factors associated with one-year outcomes. METHODS: Prospective multicenter cohort study, including ICU patients ≥16 years, admitted for ≥12 hours between July 2016-June 2019. Patients, or proxies, rated their health status before and one-year post-ICU using questionnaires. Measurements and mean results: Validated questionnaires were used to measure frailty, fatigue, new physical symptoms, anxiety and depression, post-traumatic stress disorder, cognitive impairment, and quality of life. Of the 4793 patients included, 2345 completed the questionnaires both pre- and one-year post-ICU. New physical, mental, and/or cognitive problems one-year post-ICU were experienced by 58% of the medical, 64% of the urgent surgical, and 43% of the elective surgical patients. Urgent surgical patients experienced a significant deterioration in their physical and mental functioning, whereas elective surgical patients experienced a significant improvement. Medical patients experienced an increase in symptoms of depression. A significant decline in cognitive functioning was experienced by all types of patients. Pre-ICU health status was strongly associated with post-ICU health problems. CONCLUSIONS: Overall, 50% of ICU survivors suffer from new physical, mental, and/or cognitive problems. An improved insight into the specific health problems of ICU survivors would enable more personalized post-ICU care.

4.
Anaesth Intensive Care ; 49(1): 52-61, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33530699

RESUMO

The intensive care unit (ICU) is one of the most technically advanced environments in healthcare, using a multitude of medical devices for drug administration, mechanical ventilation and patient monitoring. However, these technologies currently come with disadvantages, namely noise pollution, information overload and alarm fatigue-all caused by too many alarms. Individual medical devices currently generate alarms independently, without any coordination or prioritisation with other devices, leading to a cacophony where important alarms can be lost amongst trivial ones, occasionally with serious or even fatal consequences for patients. We have called this approach to the design of medical devices the single-device paradigm, and believe it is obsolete in modern hospitals where patients are typically connected to several devices simultaneously. Alarm rates of one alarm every four minutes for only the physiological monitors (as recorded in the ICUs of two hospitals contributing to this paper) degrades the quality of the patient's healing environment and threatens patient safety by constantly distracting healthcare professionals. We outline a new approach to medical device design involving the application of human factors principles which have been successful in eliminating alarm fatigue in commercial aviation. Our approach comprises the networked-device paradigm, comprehensive alarms and humaniform information displays. Instead of each medical device alarming separately at the patient's bedside, our proposed approach will integrate, prioritise and optimise alarms across all devices attached to each patient, display information more intuitively and hence increase alarm quality while reducing the number of alarms by an order of magnitude below current levels.

5.
Int J Obes (Lond) ; 45(3): 687-694, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33495522

RESUMO

BACKGROUND/OBJECTIVES: Obesity appears to be an independent risk factor for ICU admission and a severe disease course in COVID-19 patients. An aberrant inflammatory response and impaired respiratory function have been suggested as underlying mechanisms. We investigated whether obesity is associated with differences in inflammatory, respiratory, and clinical outcome parameters in critically ill COVID-19 patients. SUBJECTS/METHODS: Sixty-seven COVID-19 ICU patients were divided into obese (BMI ≥ 30 kg/m2, n = 18, 72% class I obesity, 28% class II obesity) and non-obese (BMI < 30 kg/m2, n = 49) groups. Concentrations of circulating interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, and IL-1 receptor antagonist (RA) were determined from ICU admission until 10 days afterward, and routine laboratory and clinical parameters were collected. RESULTS: BMI was 32.6 [31.2-34.5] and 26.0 [24.4-27.7] kg/m2 in the obese and non-obese group, respectively. Apart from temperature, which was significantly lower in obese patients (38.1 [36.9-38.9] vs. 38.7 [38.0 -39.5] °C, p = 0.02), there were no between-group differences on ICU admission. Plasma cytokine concentrations declined over time (p < 0.05 for all), but no differences between obese and non-obese patients were observed. Also, BMI did not correlate with the cytokine response (IL-6 r = 0.09, p = 0.61, TNF-α r = 0.03, p = 0.99, IP-10 r = 0.28, p = 0.11). The kinetics of clinical inflammatory parameters and respiratory mechanics were also similar in both groups. Finally, no differences in time on ventilator, ICU length of stay or 40-day mortality between obese and non-obese patients were apparent. CONCLUSIONS: In COVID-19 patients requiring mechanical ventilation in the ICU, a higher BMI is not related to a different immunological response, unfavorable respiratory mechanics, or impaired outcome.

6.
Crit Care ; 24(1): 688, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302991

RESUMO

BACKGROUND: A subset of critically ill COVID-19 patients develop a hyperinflammatory state. Anakinra, a recombinant interleukin-1 receptor antagonist, is known to be effective in several hyperinflammatory diseases. We investigated the effects of anakinra on inflammatory parameters and clinical outcomes in critically ill, mechanically ventilated COVID-19 patients with clinical features of hyperinflammation. METHODS: In this prospective cohort study, 21 critically ill COVID-19 patients treated with anakinra were compared to a group of standard care. Serial data of clinical inflammatory parameters and concentrations of multiple circulating cytokines were determined and aligned on start day of anakinra in the treatment group, and median start day of anakinra in the control group. Analysis was performed for day - 10 to + 10 relative to alignment day. Clinical outcomes were analyzed during 28 days. Additionally, three sensitivity analyses were performed: (1) using propensity score-matched groups, (2) selecting patients who did not receive corticosteroids, and (3) using a subset of the control group aimed to match the criteria (fever, elevated ferritin) for starting anakinra treatment. RESULTS: Baseline patient characteristics and clinical parameters on ICU admission were similar between groups. As a consequence of bias by indication, plasma levels of aspartate aminotransferase (ASAT) (p = 0.0002), ferritin (p = 0.009), and temperature (p = 0.001) were significantly higher in the anakinra group on alignment day. Following treatment, no relevant differences in kinetics of circulating cytokines were observed between both groups. Decreases of clinical parameters, including temperature (p = 0.03), white blood cell counts (p = 0.02), and plasma levels of ferritin (p = 0.003), procalcitonin (p = 0.001), creatinine (p = 0.01), and bilirubin (p = 0.007), were more pronounced in the anakinra group. No differences in duration of mechanical ventilation or ICU length of stay were observed between groups. Sensitivity analyses confirmed these results. CONCLUSIONS: Anakinra is effective in reducing clinical signs of hyperinflammation in critically ill COVID-19 patients. A randomized controlled trial is warranted to draw conclusion about the effects of anakinra on clinical outcomes.

7.
Ann Intensive Care ; 10(1): 115, 2020 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-32852710

RESUMO

BACKGROUND: Critical illness has detrimental effects on the diaphragm, but the impact of critical illness on other major muscles of the respiratory pump has been largely neglected. This study aimed to determine the impact of critical illness on the most important muscles of the respiratory muscle pump, especially on the expiratory muscles in children during mechanical ventilation. In addition, the correlation between changes in thickness of the expiratory muscles and the diaphragm was assessed. METHODS: This longitudinal observational cohort study performed at a tertiary pediatric intensive care unit included 34 mechanical ventilated children (> 1 month- < 18 years). Thickness of the diaphragm and expiratory muscles (obliquus interna, obliquus externa, transversus abdominis and rectus abdominis) was assessed daily using ultrasound. Contractile activity was estimated from muscle thickening fraction during the respiratory cycle. RESULTS: Over the first 4 days, both diaphragm and expiratory muscles thickness decreased (> 10%) in 44% of the children. Diaphragm and expiratory muscle thickness increased (> 10%) in 26% and 20% of the children, respectively. No correlation was found between contractile activity of the muscles and the development of atrophy. Furthermore, no correlation was found between changes in thickness of the diaphragm and the expiratory muscles (P = 0.537). Decrease in expiratory muscle thickness was significantly higher in patients failing extubation compared to successful extubation (- 34% vs - 4%, P = 0.014). CONCLUSIONS: Changes in diaphragm and expiratory muscles thickness develop rapidly after the initiation of mechanical ventilation. Changes in thickness of the diaphragm and expiratory muscles were not significantly correlated. These data provide a unique insight in the effects of critical illness on the respiratory muscle pump in children.

8.
Intensive Crit Care Nurs ; 61: 102901, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32660883

RESUMO

OBJECTIVES: To explore sound levels, alarm frequencies and the association between alarms and sound levels. DESIGN: A single center observational cross-sectional study. SETTING: Four intensive care units. MAIN OUTCOME MEASURES: Contribution of alarms: red (life threatening), yellow (indicate excess of limits) and blue (technical) to sound pressure levels dB(A) at nursing stations. RESULTS: Mean sound pressure levels differed significantly between day (56.1 ± 5.5), evening (55.1 ± 5.7) and night periods 53.6 ± 5.6; p < 0.01. 175,996 alarms were recorded of which 149,764 (85%) were yellow, 18,080 (10%) were red and 8,152 (5%) were blue. The mean sound levels without alarms (background) is 56.8 dB(A), with only red: 56.0 dB(A), only yellow: 55.6 dB(A), only blue: 56.0 dB(A) and mixed alarms: 56.3 dB(A). Yellow alarms (b = -0.93; 95% CI: -1.26 to -0.6; p < 0.001) were weakly but significantly associated with mean sound levels and lead to a slight decrease in noise level (1 dB), Red alarms (b = -0.3; 95% CI: -1.237 to 0.63; p = 0.52). The R Square of the model with all alarms was 0.01 (standard error of estimate, 6.9; p < 0.001). CONCLUSIONS: Sound levels were high during all day-periods. Alarms exceeding limits occurred most frequently. However, the contribution of alarms to sound levels measured at the nursing station is clinically limited.

9.
Am J Respir Crit Care Med ; 202(6): 830-842, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32520577

RESUMO

Rationale: Sepsis is characterized by a dysregulated immune response to infection. Norepinephrine, the cornerstone vasopressor used in septic shock, may contribute to immune dysregulation and impact host defense.Objectives: To investigate effects of norepinephrine and the alternative vasopressor vasopressin on the immune response and host defense.Methods: Leukocytes from six to nine donors were stimulated in the presence or absence of norepinephrine and vasopressin. A total of 190 C57BL/6J mice received a continuous infusion of norepinephrine or vasopressin via microosmotic pumps and were challenged with LPS or underwent cecal ligation and puncture. Thirty healthy volunteers were randomized to a 5-hour infusion of norepinephrine, vasopressin, or saline and intravenously challenged with LPS. The relationship between the norepinephrine infusion rate and the use of ß-blockers and plasma cytokines was assessed in 195 patients with septic shock.Measurements and Main Results: Norepinephrine attenuated the production of proinflammatory mediators and reactive oxygen species and augmented antiinflammatory IL-10 production both in vitro and in LPS-challenged mice. Norepinephrine infusion during cecal ligation and puncture resulted in increased bacterial dissemination to the spleen, liver, and blood. In LPS-challenged volunteers, norepinephrine enhanced plasma IL-10 concentrations and attenuated the release of the proinflammatory cytokine IFN-γ-induced protein 10. Vasopressin exerted no immunomodulatory effects across these experimental setups. In patients, higher norepinephrine infusion rates were correlated with a more antiinflammatory cytokine balance, whereas ß-blocker use was associated with a more proinflammatory cytokine balance.Conclusions: Norepinephrine dysregulates the immune response in mice and humans and compromises host defense. Therefore, it may significantly contribute to sepsis-induced immunoparalysis, whereas vasopressin does not have untoward immunologic effects.


Assuntos
Imunidade Ativa/efeitos dos fármacos , Norepinefrina/efeitos adversos , Norepinefrina/imunologia , Choque Séptico/tratamento farmacológico , Choque Séptico/imunologia , Vasoconstritores/efeitos adversos , Vasoconstritores/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/uso terapêutico , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Modelos Animais , Países Baixos , Norepinefrina/uso terapêutico , Kit de Reagentes para Diagnóstico , Vasoconstritores/uso terapêutico
10.
Crit Care Med ; 48(9): 1271-1279, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32568858

RESUMO

OBJECTIVES: Although patient's health status before ICU admission is the most important predictor for long-term outcomes, it is often not taken into account, potentially overestimating the attributable effects of critical illness. Studies that did assess the pre-ICU health status often included specific patient groups or assessed one specific health domain. Our aim was to explore patient's physical, mental, and cognitive functioning, as well as their quality of life before ICU admission. DESIGN: Baseline data were used from the longitudinal prospective MONITOR-IC cohort study. SETTING: ICUs of four Dutch hospitals. PATIENTS: Adult ICU survivors (n = 2,467) admitted between July 2016 and December 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients, or their proxy, rated their level of frailty (Clinical Frailty Scale), fatigue (Checklist Individual Strength-8), anxiety and depression (Hospital Anxiety and Depression Scale), cognitive functioning (Cognitive Failure Questionnaire-14), and quality of life (Short Form-36) before ICU admission. Unplanned patients rated their pre-ICU health status retrospectively after ICU admission. Before ICU admission, 13% of all patients was frail, 65% suffered from fatigue, 28% and 26% from symptoms of anxiety and depression, respectively, and 6% from cognitive problems. Unplanned patients were significantly more frail and depressed. Patients with a poor pre-ICU health status were more often likely to be female, older, lower educated, divorced or widowed, living in a healthcare facility, and suffering from a chronic condition. CONCLUSIONS: In an era with increasing attention for health problems after ICU admission, the results of this study indicate that a part of the ICU survivors already experience serious impairments in their physical, mental, and cognitive functioning before ICU admission. Substantial differences were seen between patient subgroups. These findings underline the importance of accounting for pre-ICU health status when studying long-term outcomes.

11.
JMIR Res Protoc ; 9(6): e16733, 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32459638

RESUMO

BACKGROUND: Controlled donation after circulatory death (cDCD) is a major source of organs for transplantation. A potential cDCD donor poses considerable challenges in terms of identification of those dying within the predefined time frame of warm ischemia after withdrawal of life-sustaining treatment (WLST) to circulatory arrest. Several attempts have been made to develop models predicting the time between treatment withdrawal and circulatory arrest. This time window determines whether organ donation can occur and influences the quality of the donated organs. However, the selected patients used for these models were not always restricted to potential cDCD donors (eg, patients with cancer or severe infections were also included). This severely limits the generalizability of those data. OBJECTIVE: The objectives of this study are the following: (1) to develop a model predicting time to death within 60 minutes in potential cDCD patients; (2) to validate and update previous prediction models on time to death after WLST; (3) to determine timing and patient characteristics that are associated with prognostication and the decision-making process that leads to initiating end-of-life care; (4) to evaluate the impact of timing of family approach on organ donation approval; and (5) to assess the influence of variation in WLST processes on postmortem organ donor potential and actual postmortem organ donors. METHODS: In this multicenter observational prospective cohort study, all patients admitted to the intensive care unit of 3 university hospitals and 3 teaching hospitals who met the criteria of the cDCD protocol as defined by the Dutch Transplant Foundation were included. The target of enrolment was set to 400 patients. Previously developed models will be refitted in our data set. To further update previous prediction models, we will apply least absolute shrinkage and selection operator (LASSO) as a tool for efficient variable selection to develop the multivariable logistic regression model. RESULTS: This protocol was funded in August 2014 by the Dutch Transplant Foundation. We expect to have the results of this study in July 2020. Patient enrolment was completed in July 2018 and data collection was completed in April 2020. CONCLUSIONS: This study will provide a robust multimodal prediction model, based on clinical and physiological parameters, that can predict time to circulatory arrest in cDCD donors. In addition, it will add valuable insight in the process of WLST in cDCD donors and will fill an important knowledge gap in this essential field of health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04123275; https://clinicaltrials.gov/ct2/show/NCT04123275. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16733.

12.
Crit Care ; 24(1): 161, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312288

RESUMO

BACKGROUND: While delirium prevalence and duration are each associated with increased 30-day, 6-month, and 1-year mortality, the association between incident ICU delirium and mortality remains unclear. We evaluated the association between both incident ICU delirium and days spent with delirium in the 28 days after ICU admission and mortality within 28 and 90 days. METHODS: Secondary cohort analysis of a randomized, double-blind, placebo-controlled trial conducted among 1495 delirium-free, critically ill adults in 14 Dutch ICUs with an expected ICU stay ≥2 days where all delirium assessments were completed. In the 28 days after ICU admission, patients were evaluated for delirium and coma 3x daily; each day was coded as a delirium day [≥1 positive Confusion Assessment Method for the ICU (CAM-ICU)], a coma day [no delirium and ≥ 1 Richmond Agitation Sedation Scale (RASS) score ≤ - 4], or neither. Four Cox-regression models were constructed for 28-day mortality and 90-day mortality; each accounted for potential confounders (i.e., age, APACHE-II score, sepsis, use of mechanical ventilation, ICU length of stay, and haloperidol dose) and: 1) delirium occurrence, 2) days spent with delirium, 3) days spent in coma, and 4) days spent with delirium and/or coma. RESULTS: Among the 1495 patients, 28 day mortality was 17% and 90 day mortality was 21%. Neither incident delirium (28 day mortality hazard ratio [HR] = 1.02, 95%CI = 0.75-1.39; 90 day mortality HR = 1.05, 95%CI = 0.79-1.38) nor days spent with delirium (28 day mortality HR = 1.00, 95%CI = 0.95-1.05; 90 day mortality HR = 1.02, 95%CI = 0.98-1.07) were significantly associated with mortality. However, both days spent with coma (28 day mortality HR = 1.05, 95%CI = 1.02-1.08; 90 day mortality HR = 1.05, 95%CI = 1.02-1.08) and days spent with delirium or coma (28 day mortality HR = 1.03, 95%CI = 1.00-1.05; 90 day mortality HR = 1.03, 95%CI = 1.01-1.06) were significantly associated with mortality. CONCLUSIONS: This analysis suggests neither incident delirium nor days spent with delirium are associated with short-term mortality after ICU admission. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT01785290 Registered 7 February 2013.


Assuntos
Delírio/complicações , Mortalidade/tendências , Idoso , Estudos de Coortes , Estado Terminal/epidemiologia , Estado Terminal/mortalidade , Delírio/epidemiologia , Delírio/mortalidade , Método Duplo-Cego , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Modelos de Riscos Proporcionais
13.
Respir Care ; 65(9): 1315-1322, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32156788

RESUMO

BACKGROUND: Patient-ventilator synchrony in patients with COPD is at risk during noninvasive ventilation (NIV). NIV in neurally-adjusted ventilatory assist (NAVA) mode improves synchrony compared to pressure support ventilation (PSV). The current study investigated patient-ventilator interaction at 2 levels of NAVA and PSV mode in subjects with COPD exacerbation. METHODS: NIV was randomly applied at 2 levels (5 and 15 cm H2O) of PSV and NAVA. Patient-ventilator interaction was evaluated by comparing airway pressure and electrical activity of the diaphragm waveforms with automated computer algorithms. RESULTS: 8 subjects were included. Trigger delay was longer in PSV high (268 ± 112 ms) than in PSV low (161 ± 118 ms, P = .043), and trigger delay during NAVA was shorter than PSV for both low support (49 ± 24 ms for NAVA, P = .035) and high support (79 ± 276 ms for NAVA, P = .003). No difference in cycling error for low and high levels of PSV (PSV low -100 ± 114 ms and PSV high 56 ± 315 ms) or NAVA (NAVA low -5 ± 18 ms, NAVA high 12 ± 36 ms) and no difference between PSV and NAVA was found. CONCLUSIONS: Increasing PSV levels during NIV caused a progressive mismatch between neural effort and pneumatic timing. Patient-ventilator interaction during NAVA was more synchronous than during PSV, independent of inspiratory support level. (ClinicalTrials.gov registration NCT01791335.).

15.
Physiol Rep ; 8(4): e14366, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32097540

RESUMO

BACKGROUND: Extracorporeally induced whole-body hyperthermia (eWBH) might be a beneficial treatment in cancer patients. Objectives of this pig study were to assess thermal distribution, (patho-)physiological effects, and safety of eWBH with a new WBH device. METHODS: Fourteen healthy adult pigs were anesthetized, mechanically ventilated, and cannulated; 12 were included in the analysis. Blood was heated in 11 pigs (one pig served as control) using a WBH device (Vithèr Hyperthermia B.V.) containing two separate fluidic circuits and a heat exchanger. Temperature was monitored on nine different sites, including the brain. Core temperature (average of 4 deep probes) was elevated to 42°C for 2 hr. RESULTS: Elevation of core body temperature to 42°C took on average (± standard deviation) 38 ± 8 min. Initially observed temperature spikes diminished after lowering maximal blood temperature to 45°C. Hereafter, brain temperature spikes never exceeded 42.5°C, mean brain temperature was at highest 41.9°C during maintenance. WBH resulted in increased heart rates and decreased mean arterial pressures. The vast amounts of fluids required to counter hypotension tended to be smaller after corticosteroid administration. Hemodialysis was started in three animals (potassium increase prevention in two and hyperkalemia treatment in one). Severe rhabdomyolysis was observed in all pigs (including the control). All animals survived the procedure until planned euthanasia 1, 6, or 24 hr post procedure. CONCLUSION: Fast induction of eWBH with homogenous thermal distribution is feasible in pigs using the Vithèr WBH device. Severe hemodynamic disturbances, rhabdomyolysis, and hyperkalemia were observed.

16.
Nurs Crit Care ; 25(5): 299-304, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31294520

RESUMO

BACKGROUND: One of the most important bottlenecks in the organ donation process worldwide is the high family refusal rate. AIMS AND OBJECTIVES: The main aim of this study was to examine whether family guidance by trained donation practitioners increased the family consent rate for organ donation. DESIGN: This was a prospective intervention study. METHODS: Intensive and coronary care unit nurses were trained in communication about donation (ie, trained donation practitioners) in two hospitals. The trained donation practitioners were appointed to guide the families of patients with a poor medical prognosis. When the patient became a potential donor, the trained donation practitioner was there to guide the family in making a well-considered decision about donation. We compared the family consent rate for donation with and without the guidance of a trained donation practitioner. RESULTS: The consent rate for donation with guidance by a trained donation practitioner was 58.8% (20/34), while the consent rate without guidance by a trained donation practitioner was 41.4% (41/99, P = 0.110) in those patients where the family had to decide on organ donation. CONCLUSIONS: Our data suggest that family guidance by a trained donation practitioner could benefit consent rates for organ donation. RELEVANCE TO CLINICAL PRACTICE: Trained nurses play an important role in supporting the families of patients who became potential donors to guide them through the decision-making process after organ donation request.

17.
Shock ; 53(2): 171-174, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31008870

RESUMO

AIM: Comparing the effects of different vasopressors in septic shock patients is hampered by high heterogeneity and the fact that current guidelines dictate the use of norepinephrine. Herein, we studied the effects of three vasopressor agents, norepinephrine, phenylephrine, and vasopressin, on the macro- and microcirculation during experimental human endotoxemia, a standardized, controlled model of systemic inflammation in humans in vivo. METHODS: We performed a randomized controlled study in which 40 healthy male volunteers were assigned to a 5-h infusion of either 0.05 µg/kg/min norepinephrine (n = 10), 0.5 µg/kg/min phenylephrine (n = 10), 0.04 IU/min vasopressin (n = 10), or saline (n = 10), starting 1 h before intravenous administration of 2 ng/kg lipopolysaccharide (LPS). The macrocirculation was monitored using arterial catheter-derived parameters with additional blood pressure waveform contour analysis (PCA) until 4.5 h following LPS administration. Sublingual microcirculatory density and flow were assessed using a handheld video microscope until 6 h post-LPS. RESULTS: LPS administration affected all macrocirculatory and microcirculatory parameters. The LPS-induced decrease in blood pressure and systemic vascular resistance (SVR) was refractory to low-dose norepinephrine and phenylephrine, and to a lesser extent, to vasopressin. Only vasopressin exerted effects on PCA parameters compared with placebo, by mitigating the LPS-induced decrease in diastolic blood pressure by stabilizing SVR and cardiac output. The endotoxemia-induced decreased indices of microvascular flow and density were not influenced by vasopressor therapy. CONCLUSIONS: In a highly controlled model of systemic inflammation in humans in vivo, a 5-h infusion of various vasopressors revealed distinctive effects on macrohemodynamic variables without affecting the sublingual microcirculation.

18.
Eur J Emerg Med ; 27(3): 197-201, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31714472

RESUMO

OBJECTIVE: To identify and compare manual and load-distributing band (LDB) cardiopulmonary resuscitation (CPR)-related injuries. METHODS: Retrospective observational cohort study. Adult, nontraumatic deaths with a postmortem computed tomography scan (PMCT) performed were classified into two groups: deceased after LDB CPR or after manual CPR. PMCT scans were reviewed for thoracoabdominal injuries such as fractures, pneumothorax and hemorrhage. The injuries between groups were compared. RESULTS: LDB CPR (n = 43) showed increased incidences of posterior rib fractures (53 vs 18%, P = 0.006), pneumothorax (23 vs 4%, P = 0.04) and more pericardial fluid (median 12 vs 6 mm, P = 0.002) compared with manual CPR (n = 29). Multivariable regression analysis revealed that LDB CPR was significantly associated with posterior rib fractures [odds ratio (OR) 5.37, 95% confidence interval (CI): 1.44-20.09, P = 0.01). Pneumothorax (OR 6.80, 95% CI: 0.73-62.99, P = 0.09) and the amount of pericardial fluid (OR 3.40, 95% CI: 0.20-56.32) were not significantly associated with LDB CPR. No significant difference was found for anterolateral rib fractures, sternal fractures, vertebral fractures, pleural fluid, hemothorax, hemopericardium, pneumoperitoneum, perihepatic, perisplenic and perirenal hemorrhage. CONCLUSION: Rib fractures, sternal fractures, hemothorax and hemopericardium are common CPR-related injuries. LDB CPR is significantly associated with more posterior rib fractures and a trend toward more pneumothoraces is observed when compared with manual CPR. This knowledge is important for caretakers in the case of ongoing CPR, as a pneumothorax may attribute to not achieving persistent return of spontaneous circulation, and to improve postresuscitation care of survivors.

19.
Neurology ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33443134

RESUMO

OBJECTIVE: We report a case series of patients with prolonged but reversible unconsciousness following COVID-19 related severe respiratory failure. METHODS: A case series of patients who were admitted to the ICU due to COVID-19 related acute respiratory failure is described. RESULTS: After cessation of sedatives the described cases all showed a prolonged comatose state. Diagnostic neurological work-up did not show signs of devastating brain injury. The clinical pattern of awakening started with early eye opening without obeying commands and persistent flaccid weakness in all cases. Time between cessation of sedatives to the first moment of being fully responsive with obeying commands ranged from 8 to 31 days. CONCLUSION: Prolonged unconsciousness in patients with severe respiratory failure due to COVID-19 can be fully reversible warranting a cautious approach for prognostication based on a prolonged state of unconsciousness.

20.
Physiol Rep ; 7(23): e14301, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31814327

RESUMO

Clinical data suggests that heart rate (HR) control with selective ß1-blockers may improve cardiac function during septic shock. However, it seems counterintuitive to start ß-blocker infusion in a shock state when organ blood flow is already low or insufficient. Therefore, we studied the effects of HR control with esmolol, an ultrashort- acting ß1-selective adrenoceptor antagonist, on renal blood flow (RBF) and renal autoregulation during early septic shock. In 10 healthy sheep, sepsis was induced by continuous i.v. administration of lipopolysaccharide, while maintained under anesthesia and mechanically ventilated. After successful resuscitation of the septic shock with fluids and vasoactive drugs, esmolol was infused to reduce HR with 30% and was stopped 30-min after reaching this target. Arterial and venous pressures, and RBF were recorded continuously. Renal autoregulation was evaluated by the response in RBF to renal perfusion pressure (RPP) in both the time domain and frequency domain. During septic shock, ß-blockade with esmolol significantly increased the pressure dependency of RBF to RPP. Stopping esmolol showed the reversibility of the impaired renal autoregulation. Showing that clinical diligence and caution are necessary when treating septic shock with esmolol in the acute phase since esmolol reduced RPP to critical values thereby significantly reducing RBF.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Frequência Cardíaca , Propanolaminas/uso terapêutico , Circulação Renal , Choque Séptico/tratamento farmacológico , Lesão Renal Aguda/etiologia , Antagonistas Adrenérgicos beta/administração & dosagem , Animais , Feminino , Infusões Intravenosas , Lipopolissacarídeos/toxicidade , Propanolaminas/administração & dosagem , Ovinos , Choque Séptico/complicações , Choque Séptico/etiologia
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