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1.
JAMA ; 331(14): 1185-1194, 2024 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-38501214

RESUMEN

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.


Asunto(s)
COVID-19 , Adulto , Humanos , Masculino , Anciano , Femenino , COVID-19/terapia , COVID-19/etiología , Oxígeno , Respiración Artificial , Terapia por Inhalación de Oxígeno/métodos , Hipoxia/etiología , Hipoxia/terapia
2.
Acta Anaesthesiol Scand ; 68(1): 130-136, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37691474

RESUMEN

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.


Asunto(s)
Furosemida , Desequilibrio Hidroelectrolítico , Adulto , Humanos , Furosemida/uso terapéutico , Cuidados Críticos/métodos , Unidades de Cuidados Intensivos , Resultado del Tratamiento
3.
Acta Anaesthesiol Scand ; 67(10): 1383-1394, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37737652

RESUMEN

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.


Asunto(s)
Insuficiencia Respiratoria , Adulto , Humanos , Insuficiencia Respiratoria/terapia , Respiración Artificial , Pulmón , Unidades de Cuidados Intensivos , Respiración
4.
Intensive Care Med ; 49(7): 820-830, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37330928

RESUMEN

PURPOSE: To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial. METHODS: We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. RESULTS: Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. CONCLUSIONS: Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.


Asunto(s)
Choque Séptico , Humanos , Adulto , Choque Séptico/terapia , Calidad de Vida , Unidades de Cuidados Intensivos , Cuidados Críticos , Sobrevivientes
5.
J Intensive Care Med ; 38(10): 966-974, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37186782

RESUMEN

Rationale: Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. Objective: We examined the correlation between bioimpedance and organ dysfunction in patients with septic shock. Methods: Prospective observational study of adult intensive care unit patients fulfilling the sepsis-3 criteria. Bioimpedance was measured using a body composition monitor (BCM) and BioScan Touch i8 (MBS). We measured impedance at inclusion and after 24 h and reported the impedance, change in impedance, bioimpedance-derived fluid balance, and changes in bioimpedance-derived fluid balance. Organ markers on respiratory, circulatory, and kidney function and overall disease severity were ascertained on days 1-7. The effect of bioimpedance on the change in organ function was assessed by mixed effects linear models. We considered P < .01 as significant. Measurements and Main Results: Forty-nine patients were included. None of the single baseline measurements or derived fluid balances were associated with the course of organ dysfunction. Changes in impedance were associated with the course of overall disease severity (P < .001; with MBS), and with changes in noradrenaline dose (P < .001; with MBS) and fluid balance (P < .001; with BCM). The changes in bioimpedance-derived fluid balance were associated with changes in noradrenaline dose (P < .001; with BCM), cumulative fluid balances (P < .001; with MBS), and lactate concentrations (P < .001; with BCM). Conclusions: Changes in bioimpedance were correlated with the duration of overall organ failure, circulatory failure, and fluid status. Single measurements of bioimpedance were not associated with any changes in organ dysfunction.


Asunto(s)
Choque Séptico , Desequilibrio Hidroelectrolítico , Adulto , Humanos , Choque Séptico/complicaciones , Choque Séptico/terapia , Insuficiencia Multiorgánica/etiología , Composición Corporal , Desequilibrio Hidroelectrolítico/etiología , Norepinefrina
6.
7.
Acta Anaesthesiol Scand ; 67(4): 470-478, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36636797

RESUMEN

BACKGROUND: Salt and water accumulation leading to fluid overload is associated with increased mortality in intensive care unit (ICU) patients, but diuretics' effects on patient outcomes are uncertain. In this first version of the GODIF trial, we aimed to assess the effects of goal-directed fluid removal with furosemide versus placebo in adult ICU patients with fluid overload. METHODS: We conducted a multicentre, randomised, stratified, parallel-group, blinded, placebo-controlled trial in clinically stable, adult ICU patients with at least 5% fluid overload. Participants were randomised to furosemide versus placebo infusion aiming at achieving neutral cumulative fluid balance as soon as possible. The primary outcome was the number of days alive and out of the hospital at 90 days. RESULTS: The trial was terminated after the enrolment of 41 of 1000 participants because clinicians had difficulties using cumulative fluid balance as the only estimate of fluid status (32% of participants had their initially registered cumulative fluid balance adjusted and 29% experienced one or more protocol violations). The baseline cumulative fluid balance was 6956 ml in the furosemide group and 6036 ml in the placebo group; on day three, the cumulative fluid balances were 1927 ml and 5139 ml. The median number of days alive and out of hospital at day 90 was 50 days in the furosemide group versus 45 days in the placebo group (mean difference 1 day, 95% CI -19 to 21, p-value .94). CONCLUSIONS: The use of cumulative fluid balance as the only estimate of fluid status appeared too difficult to use in clinical practice. We were unable to provide precise estimates for any outcomes as only 4.1% of the planned sample size was randomised.


Asunto(s)
Furosemida , Desequilibrio Hidroelectrolítico , Adulto , Humanos , Furosemida/uso terapéutico , Objetivos , Diuréticos/uso terapéutico , Cuidados Críticos/métodos
8.
Front Med (Lausanne) ; 9: 1067162, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36507497

RESUMEN

Introduction: Fluid overload in patients in the intensive care unit (ICU) is associated with higher mortality. There are few randomized controlled trials to guide physicians in treating patients with fluid overload in the ICU, and no guidelines exist. We aimed to elucidate how ICU physicians from Nordic countries define, assess, and treat fluid overload in the ICU. Materials and methods: We developed an online questionnaire with 18 questions. The questions were pre-tested and revised by specialists in intensive care medicine. Through a network of national coordinators. The survey was distributed to a wide range of Nordic ICU physicians. The distribution started on January 5th, 2022 and ended on May 6th, 2022. Results: We received a total of 1,066 responses from Denmark, Norway, Finland, Sweden, and Iceland. When assessing fluid status, respondents applied clinical parameters such as clinical examination findings, cumulative fluid balance, body weight, and urine output more frequently than cardiac/lung ultrasound, radiological appearances, and cardiac output monitoring. A large proportion of the respondents agreed that a 5% increase or more in body weight from baseline supported the diagnosis of fluid overload. The preferred de-resuscitation strategy was diuretics (91%), followed by minimization of maintenance (76%) and resuscitation fluids (71%). The majority declared that despite mild hypotension, mild hypernatremia, and ongoing vasopressor, they would not withhold treatment of fluid overload and would continue diuretics. The respondents were divided when it came to treating fluid overload with loop diuretics in patients receiving noradrenaline. Around 1% would not administer noradrenaline and diuretics simultaneously and 35% did not have a fixed upper limit for the dosage. The remaining respondents 63% reported different upper limits of noradrenaline infusion (0.05-0.50 mcg/kg/min) when administering loop diuretics. Conclusion: Self-reported practices among Nordic ICU physicians when assessing, diagnosing, and treating fluid overload reveals variability in the practice. A 5% increase in body weight was considered a minimum to support the diagnosis of fluid overload. Clinical examination findings were preferred for assessing, diagnosing and treating fluid overload, and diuretics were the preferred treatment modality.

9.
Acta Anaesthesiol Scand ; 66(9): 1138-1145, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35898170

RESUMEN

BACKGROUND: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of goal directed fluid removal with furosemide versus placebo in ICU patients with fluid overload. METHODS: An investigator-initiated, international, randomised, stratified, blinded, parallel-group trial allocating 1000 adult ICU patients with fluid overload to infusion of furosemide versus placebo. The goal is to achieve a neutral fluid balance. The primary outcome is days alive and out of hospital 90 days after randomisation. Secondary outcomes are all-cause mortality at day 90 and 1-year after randomisation; days alive at day 90 without life support; number of participants with one or more serious adverse events or reactions; health-related quality of life and cognitive function at 1-year follow-up. A sample size of 1000 participants is required to detect an improvement of 8% in days alive and out of hospital 90 days after randomisation with a power of 90% and a risk of type 1 error of 5%. The conclusion of the trial will be based on the point estimate and 95% confidence interval; dichotomisation will not be used. CLINICALTRIALS: gov identifier: NCT04180397. PERSPECTIVE: The GODIF trial will provide important evidence of possible benefits and harms of fluid removal with furosemide in adult ICU patients with fluid overload.


Asunto(s)
Furosemida , Desequilibrio Hidroelectrolítico , Adulto , Cuidados Críticos/métodos , Furosemida/uso terapéutico , Objetivos , Humanos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
10.
Ann Intensive Care ; 12(1): 52, 2022 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-35696008

RESUMEN

BACKGROUND: Fluid overload is a risk factor for organ dysfunction and death in intensive care unit (ICU) patients, but no guidelines exist for its management. We systematically reviewed benefits and harms of a single loop diuretic, the predominant treatment used for fluid overload in these patients. METHODS: We conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) of a single loop diuretic vs. other interventions reported in randomised clinical trials, adhering to our published protocol, the Cochrane Handbook, and PRISMA statement. We assessed the risks of bias with the ROB2-tool and certainty of evidence with GRADE. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020184799). RESULTS: We included 10 trials (804 participants), all at overall high risk of bias. For loop diuretics vs. placebo/no intervention, we found no difference in all-cause mortality (relative risk (RR) 0.72, 95% confidence interval (CI) 0.49-1.06; 4 trials; 359 participants; I2 = 0%; TSA-adjusted CI 0.15-3.48; very low certainty of evidence). Fewer serious adverse events were registered in the group treated with loop diuretics (RR 0.81, 95% CI 0.66-0.99; 6 trials; 476 participants; I2 = 0%; very low certainty of evidence), though contested by TSA (TSA-adjusted CI 0.55-1.20). CONCLUSIONS: The evidence is very uncertain about the effect of loop diuretics on mortality and serious adverse events in adult ICU patients with fluid overload. Loop diuretics may reduce the occurrence of these outcomes, but large randomised placebo-controlled trials at low risk of bias are needed.

11.
Acta Anaesthesiol Scand ; 65(9): 1155-1167, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34036559

RESUMEN

OBJECTIVE: Precise measurements of fluid status lack valid methods. Bioimpedance is an attractive diagnostic tool because it is noninvasive, quick, and relatively cheap. This systematic review aims to assess the existing evidence of bioimpedance as an accurate measure of fluid status in critically ill patients. DATA SOURCES: PubMed and Embase up till March 2021 were systematically searched (PROSPERO: CRD42020157436). STUDY SELECTION: Eligibility criteria were studies reporting original data from cohorts of adult patients in intensive care units and doing at least one whole-body bioimpedance and one reference test. In addition, studies assessing internal reproducibility were included. DATA EXTRACTION: An extraction form was designed for the purpose. DATA SYNTHESIS: Nine hundred five studies were screened for eligibility, and 28 studies, comprising 1482 individual patients, were included in the final analysis. Eight studies compared bioimpedance with a gold standard, and two of those reported the results adequate. We found a low mean difference, but the 95% limits of agreements had wide limits. The remaining studies applied different surrogates as reference tests. Correlations ranged from 0.05 to 0.99. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty of evidence for all outcomes was very low. CONCLUSIONS: The accuracy of bioimpedance as a measure for fluids in critically ill patients in the intensive care unit cannot be determined. Due to the lack of a gold standard, numerous studies compared bioimpedance with surrogate outcomes with great variability in both designs and results. Assessing the internal reproducibility of bioimpedance had the same limitations, but the studies overall reported good internal reproducibility.


Asunto(s)
Enfermedad Crítica , Fluidoterapia , Unidades de Cuidados Intensivos , Adulto , Humanos , Reproducibilidad de los Resultados
12.
Acta Anaesthesiol Scand ; 64(9): 1327-1334, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32531069

RESUMEN

BACKGROUND: In the intensive care unit, fluid overload is frequent and a risk factor for organ dysfunction and increased mortality. Primarily, lung and kidney functions may be impaired by fluid overload resulting in acute respiratory failure and acute kidney injury. No clinical guidelines exist for treatment of fluid overload in intensive care patients. Loop diuretics, most often furosemide, appear to be the most frequently used pharmacological intervention. The aim of this protocol is to describe the methods of a systematic review assessing the evidence of treatment with loop diuretics in adult intensive care patients with fluid overload. METHODS: We will conduct a systematic review with meta-analysis and report it according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statements, use the recommendations of the Cochrane Handbook and assess the quality of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. We will include randomised clinical trials identified through searches of major international databases and trial registers. Two authors will independently screen and select trials for inclusion, extract data and assess the methodological quality using the Cochrane risk of bias tool. Extracted data will be analysed using Review Manager and Trial Sequential Analysis. The protocol is registered at PROSPERO. DISCUSSION: We aim to provide reliable evidence on the use of loop diuretics in adult intensive care patients with fluid overload to guide clinicians, decision makers and trialists on clinical practice.


Asunto(s)
Insuficiencia Cardíaca , Desequilibrio Hidroelectrolítico , Adulto , Cuidados Críticos , Humanos , Unidades de Cuidados Intensivos , Metaanálisis como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/uso terapéutico , Revisiones Sistemáticas como Asunto
13.
JAMA ; 322(15): 1476-1485, 2019 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-31577035

RESUMEN

IMPORTANCE: Norepinephrine, the first-line vasopressor for septic shock, is not always effective and has important catecholaminergic adverse effects. Selepressin, a selective vasopressin V1a receptor agonist, is a noncatecholaminergic vasopressor that may mitigate sepsis-induced vasodilatation, vascular leakage, and edema, with fewer adverse effects. OBJECTIVE: To test whether selepressin improves outcome in septic shock. DESIGN, SETTING, AND PARTICIPANTS: An adaptive phase 2b/3 randomized clinical trial comprising 2 parts that included adult patients (n = 868) with septic shock requiring more than 5 µg/min of norepinephrine. Part 1 used a Bayesian algorithm to adjust randomization probabilities to alternative selepressin dosing regimens and to trigger transition to part 2, which would compare the best-performing regimen with placebo. The trial was conducted between July 2015 and August 2017 in 63 hospitals in Belgium, Denmark, France, the Netherlands, and the United States, and follow-up was completed by May 2018. INTERVENTIONS: Random assignment to 1 of 3 dosing regimens of selepressin (starting infusion rates of 1.7, 2.5, and 3.5 ng/kg/min; n = 585) or to placebo (n = 283), all administered as continuous infusions titrated according to hemodynamic parameters. MAIN OUTCOMES AND MEASURES: Primary end point was ventilator- and vasopressor-free days within 30 days (deaths assigned zero days) of commencing study drug. Key secondary end points were 90-day mortality, kidney replacement therapy-free days, and ICU-free days. RESULTS: Among 868 randomized patients, 828 received study drug (mean age, 66.3 years; 341 [41.2%] women) and comprised the primary analysis cohort, of whom 562 received 1 of 3 selepressin regimens, 266 received placebo, and 817 (98.7%) completed the trial. The trial was stopped for futility at the end of part 1. Median study drug duration was 37.8 hours (IQR, 17.8-72.4). There were no significant differences in the primary end point (ventilator- and vasopressor-free days: 15.0 vs 14.5 in the selepressin and placebo groups; difference, 0.6 [95% CI, -1.3 to 2.4]; P = .30) or key secondary end points (90-day mortality, 40.6% vs 39.4%; difference, 1.1% [95% CI, -6.5% to 8.8%]; P = .77; kidney replacement therapy-free days: 18.5 vs 18.2; difference, 0.3 [95% CI, -2.1 to 2.6]; P = .85; ICU-free days: 12.6 vs 12.2; difference, 0.5 [95% CI, -1.2 to 2.2]; P = .41). Adverse event rates included cardiac arrhythmias (27.9% vs 25.2% of patients), cardiac ischemia (6.6% vs 5.6%), mesenteric ischemia (3.2% vs 2.6%), and peripheral ischemia (2.3% vs 2.3%). CONCLUSIONS AND RELEVANCE: Among patients with septic shock receiving norepinephrine, administration of selepressin, compared with placebo, did not result in improvement in vasopressor- and ventilator-free days within 30 days. Further research would be needed to evaluate the potential role of selepressin for other patient-centered outcomes in septic shock. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02508649.

14.
Pharmacogenet Genomics ; 26(7): 351-6, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27031121

RESUMEN

INTRODUCTION: Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine. METHODS: The Danish Cholinesterase Research Unit registers patients with prolonged duration of action to succinylcholine and mivacurium. Patients were studied if they had equivocal phenotypes on the basis of BChE activity, biochemical inhibitor reactions and with pedigree if possible. Complete nucleotide sequencing was performed to describe the genotype and pedigree was used to separate the alleles. Multiple sequence alignment of BChE was performed for comparison with other species. RESULTS: Genotyping indicated seven novel mutations in the BCHE (I373T, G467S, W518R, L184S, V421A, M462I and R577H). CONCLUSION: We have found seven new variants of the BCHE, which seem to reduce the activity of BChE in patients undergoing anaesthesia involving succinylcholine or mivacurium.


Asunto(s)
Butirilcolinesterasa/genética , Isoquinolinas/farmacología , Mutación/genética , Fármacos Neuromusculares Despolarizantes/farmacología , Fármacos Neuromusculares no Despolarizantes/farmacología , Succinilcolina/farmacología , Femenino , Genotipo , Humanos , Masculino , Mivacurio , Linaje
15.
Emerg Med J ; 30(3): 223-5, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22505303

RESUMEN

INTRODUCTION: Opioid overdose is commonly treated by prehospital emergency services and the majority of the patients are discharged immediately after treatment and a short observation period. There is a minor risk for rebound opioid toxicity and other life-threatening conditions might occur after such episodes. The authors describe the short-term outcome and identify risk factors for death within 48 h after prehospital treatment of opioid overdose in Copenhagen, the capital of Denmark. METHODS: Data on all cases of opioid overdose treated by the medical emergency care unit between 1994 and 2003 were recorded prospectively. Risk factors for death within 48 h after initial medical emergency care unit contact were analysed in a multivariable logistic regression analysis. RESULTS: The authors recorded 4762 episodes of opioid overdose, covering 1967 unique identified patients. A total of 78 patients (8.4%, 95% CI 7.0 to 10.4) died within 48 h in the period 1999-2003, and 85% (66/78) of these had cardiac arrest and died. The authors found age >50 years and overdose during the weekend significantly associated with 48-h mortality. Gender, former episodes of opioid overdose, time of the day, month or year were not significantly associated with increased mortality. CONCLUSIONS: The author found a 48-hours mortality of 8.4%. Advanced age and opioid overdose in the weekends were significant risk factors. Release on scene after treatment was associated with a very small risk.


Asunto(s)
Sobredosis de Droga/mortalidad , Servicios Médicos de Urgencia , Tratamiento de Urgencia , Trastornos Relacionados con Opioides/mortalidad , Trastornos Relacionados con Opioides/terapia , Adulto , Factores de Edad , Dinamarca/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Estudios Prospectivos , Factores de Riesgo
16.
Dan Med J ; 59(4): A4415, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22459720

RESUMEN

INTRODUCTION: In Copenhagen, Denmark, patients in need of prehospital emergency assistance dial 112 and may then receive evaluation and treatment by physicians (from the Mobile Emergency Care Unit (MECU)). ST-elevation myocardial infarction (STEMI) is a severe condition leaving only a limited time frame to deliver optimal care in the form of percutaneous transluminal coronary angioplasty. In theory, all patients with chest pain could have STEMI. The aim of this study was to study which of the patients suspected of having acute cardiac disease based on the 112 calls and met by the MECU were given a cardiac diagnosis on the scene and, furthermore, to compare these on-scene diagnoses with the primary discharge diagnoses from hospital. MATERIAL AND METHODS: This was a retrospective study based on medical records from the MECU and the National Patient Registry. The study period covered six months in 2008 during which all 112-alarms to acute cardiac disease cases were met by the MECU were included. The study population comprised 1,219 patients. RESULTS: A total of 780 (66.3%) of the dispatches resulted in a cardiac diagnosis by the MECU physician. 77% of the admitted patients were diagnosed with a primary cardiac disease on discharge. These were categorized into three groups: acute coronary syndrome (314 patients, 57%), cardiac arrhythmias (58 patients, 10%), and other cardiac disorders (183 patients, 33%). Only 46% of the study population was discharged from hospital with a cardiac diagnosis CONCLUSION: Only half of the included patients were discharged from hospital with a cardiac diagnosis, which leaves room for improvement. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.


Asunto(s)
Ambulancias/estadística & datos numéricos , Errores Diagnósticos/estadística & datos numéricos , Servicios Médicos de Urgencia/métodos , Infarto del Miocardio/diagnóstico , Alta del Paciente/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ambulancias/normas , Angioplastia Coronaria con Balón , Niño , Preescolar , Diagnóstico Tardío , Dinamarca , Servicios Médicos de Urgencia/normas , Servicios Médicos de Urgencia/estadística & datos numéricos , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Sistema de Registros , Estudios Retrospectivos , Factores de Tiempo , Adulto Joven
17.
Ugeskr Laeger ; 173(42): 2654-5, 2011 Oct 17.
Artículo en Danés | MEDLINE | ID: mdl-22027169

RESUMEN

Adult-onset Still's disease is a rare systemic inflammatory illness. The condition is difficult to diagnose because the illness can resemble sepsis and other well known conditions. This case report concerns a 67 year-old woman with adult-onset Still's disease in two rare manifestations: acute respiratory distress syndrome and neurological manifestation in the form of Gullain Barré syndrome.


Asunto(s)
Enfermedad de Still del Adulto/diagnóstico , Anciano , Diagnóstico Diferencial , Femenino , Síndrome de Guillain-Barré/diagnóstico , Humanos , Síndrome de Dificultad Respiratoria/diagnóstico , Sepsis/diagnóstico
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