RESUMO
: Changes in fibrinolysis following subarachnoid haemorrhage (SAH) and intracerebral haemorrhage (ICH) are sparsely investigated. To investigate fibrinolysis in the acute phase in SAH and ICH patients compared with healthy individuals, fibrinolysis after 24âh in ICH patients and the in-vivo effect of tranexamic acid (TXA) on fibrinolysis in SAH patients. Further, ex-vivo studies were performed by addition of several haemostatic agents to blood samples obtained at admission. Blood was sampled from 46 SAH and 41 ICH patients upon admission. In ICH patients, a second blood sample was obtained 24âh after symptom onset, and in SAH patients after TXA treatment. A sex-matched healthy control group was used for comparison. Fibrinolysis and clot stability were assessed by a dynamic fibrin clot lysis assay, and measurements of plasminogen activator inhibitor I, tissue plasminogen activator and coagulation factor XIII were performed. On admission, no difference in lysis time was found in SAH or ICH patients compared with healthy controls (all P values >0.15). For SAH and ICH patients, median plasminogen activator inhibitor I, tissue plasminogen activator and factor XIII levels were within the reference intervals. In ICH patients, lysis time remained within 24âh after symptom onset (Pâ=â0.63). In SAH patients, the clot lysis curve showed a complete block of fibrinolysis after TXA administration. Ex-vivo addition of solulin and prothrombin complex concentrate reduced fibrinolysis (Pâ<â0.001). SAH and ICH patients showed no hyperfibrinolysis on admission. Fibrinolysis remained normal in ICH patients, and TXA treatment obliterated fibrinolysis in SAH patients.
Assuntos
Hemorragia Cerebral/sangue , Fibrinólise , Hemorragia Subaracnóidea/sangue , Adulto , Idoso , Fatores de Coagulação Sanguínea/farmacologia , Estudos de Casos e Controles , Feminino , Tempo de Lise do Coágulo de Fibrina , Fibrinólise/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ácido Tranexâmico/farmacologiaRESUMO
BACKGROUND: The ability to achieve hemostasis after spontaneous subarachnoid hemorrhage (SAH) plays a pivotal role in outcome. Changes in coagulation in the early hours after SAH have been only sparsely investigated. OBJECTIVE: To investigate changes in coagulation after SAH and illuminate underlying mechanisms. METHODS: We enrolled 46 patients with spontaneous aneurysmal SAH. Blood samples were collected at admission and 24 hours after symptom onset. Thromboelastometry (ROTEM) was performed using the standard assays EXTEM, INTEM, and FIBTEM. Platelet maximum clot elasticity was calculated based on ROTEM results. Thrombin generation, levels of thrombin-antithrombin complex, fibrinogen, and coagulation factor XIII were measured. All data were compared with a gender-matched healthy control group. RESULTS: At admission (median, 3 hours 39 minutes from symptom onset), maximum clot firmness (EXTEM, P < 0.0001; INTEM, P = 0.08; FIBTEM, P < 0.0001) and platelet maximum clot elasticity (P < 0.0001) were higher in patients with SAH than in healthy controls. Thrombin generation showed higher, although nonsignificant, endogenous thrombin potential in patients with SAH than in healthy controls (P = 0.06), and thrombin-antithrombin complex levels were above the reference interval. Median fibrinogen and coagulation factor XIII levels were both within the reference parameters and remained increased 24 hours after symptom onset, whereas endogenous thrombin potential (P = 0.01) and thrombin-antithrombin complex levels decreased (P < 0.0001). CONCLUSIONS: Patients with SAH were in a hypercoagulable state at admission and remained so 24 hours after SAH. Increased clot firmness could be caused by increased platelet function, because platelet maximum clot elasticity was increased despite normal fibrinogen and coagulation factor XIII levels.
Assuntos
Hemorragia Subaracnóidea/sangue , Hemorragia Subaracnóidea/complicações , Trombofilia/complicações , Trombofilia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea , Testes de Coagulação Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , TromboelastografiaRESUMO
BACKGROUND: Intracerebral hemorrhage (ICH) causes death or disability and the incidence increases with age. Knowledge of acute hemostatic function in patients with ICH without anticoagulant and antiplatelet therapy is sparse. Increased knowledge of the coagulation profile in the acute phase of ICH could improve acute treatment and recovery. We investigated coagulation at admission and changes in coagulation during the first 24hours after symptom onset. METHODS: Enrolled were 41 ICH patients without anticoagulant or antiplatelet therapy admitted to Aarhus University Hospital, Denmark. Blood samples were collected at admission, 6, and 24hours after symptom onset. Thromboelastometry (ROTEM), thrombin generation, and thrombin-antithrombin (TAT) complex were analyzed. Clinical outcome was evaluated using the National Institute of Health Stroke Scale, the Modified Rankin Score, and mortality. RESULTS: At admission, compared with healthy individuals, ICH patients had increased maximum clot firmness (EXTEM P < .0001; INTEM P < .0001; FIBTEM P < .0001), increased platelet maximum clot elasticity (P < .0001) in ROTEM, higher peak thrombin (P < .0001) and endogenous thrombin potential (Pâ¯=â¯.01) in thrombin generation, and elevated TAT complex levels. During 24hours after significantly, while thrombin generation showed decreased peak thrombin (P < .0001) and endogenous thrombin potential (P < .0001). Coagulation test results did not differ between patients when stratified according to clinical outcome. CONCLUSIONS: ICH patients without anticoagulant or antiplatelet therapy demonstrated activated coagulation at admission and within 24hours after symptom onset.
Assuntos
Coagulação Sanguínea , Hemorragia Cerebral/sangue , Peptídeo Hidrolases/sangue , Tromboelastografia , Trombina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antitrombina III , Biomarcadores/sangue , Estudos de Casos e Controles , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/fisiopatologia , Dinamarca , Avaliação da Deficiência , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND: Animal models of serious infection suggest that 24 h of induced hypothermia improves circulatory and respiratory function and reduces mortality. We tested the hypothesis that a reduction of core temperature to 32-34°C attenuates organ dysfunction and reduces mortality in ventilator-dependent patients with septic shock. METHODS: In this randomised, controlled, open-label trial, we recruited patients from ten intensive care units (ICUs) in three countries in Europe and North America. Inclusion criteria for patients with severe sepsis or septic shock were a mean arterial pressure of less than 70 mm Hg, mechanical ventilation in an ICU, age at least 50 years, predicted length of stay in the ICU at least 24 h, and recruitment into the study within 6 h of fulfilling inclusion criteria. Exclusion criteria were uncontrolled bleeding, clinically important bleeding disorder, recent open surgery, pregnancy or breastfeeding, or involuntary psychiatric admission. We randomly allocated patients 1:1 (with variable block sizes ranging from four to eight; stratified by predictors of mortality, age, Acute Physiology and Chronic Health Evaluation II score, and study site) to routine thermal management or 24 h of induced hypothermia (target 32-34°C) followed by 48 h of normothermia (36-38°C). The primary endpoint was 30 day all-cause mortality in the modified intention-to-treat population (all randomly allocated patients except those for whom consent was withdrawn or who were discovered to meet an exclusion criterion after randomisation but before receiving the trial intervention). Patients and health-care professionals giving the intervention were not masked to treatment allocation, but assessors of the primary outcome were. This trial is registered with ClinicalTrials.gov, number NCT01455116. FINDINGS: Between Nov 1, 2011, and Nov 4, 2016, we screened 5695 patients. After recruitment of 436 of the planned 560 participants, the trial was terminated for futility (220 [50%] randomly allocated to hypothermia and 216 [50%] to routine thermal management). In the hypothermia group, 96 (44·2%) of 217 died within 30 days versus 77 (35·8%) of 215 in the routine thermal management group (difference 8·4% [95% CI -0·8 to 17·6]; relative risk 1·2 [1·0-1·6]; p=0·07]). INTERPRETATION: Among patients with septic shock and ventilator-dependent respiratory failure, induced hypothermia does not reduce mortality. Induced hypothermia should not be used in patients with septic shock. FUNDING: Trygfonden, Lundbeckfonden, and the Danish National Research Foundation.
Assuntos
Hipotermia Induzida/mortalidade , Insuficiência Respiratória/terapia , Choque Séptico/terapia , APACHE , Idoso , Europa (Continente) , Feminino , Humanos , Hipotermia Induzida/métodos , Unidades de Terapia Intensiva , Masculino , América do Norte , Respiração Artificial/métodos , Respiração Artificial/mortalidade , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/mortalidade , Choque Séptico/complicações , Choque Séptico/mortalidade , Resultado do TratamentoRESUMO
Neurological injury develops over days following cardiac arrest (CA); however, the exact mechanisms remain unknown. After stroke or trauma, the progression of neurological injury is associated with cortical-spreading depolarizations (CSDs). The objective was to investigate whether CA and subsequent resuscitation in rats are associated with 1) the development of spontaneous negative direct current (DC) shifts indicative of CSDs, and 2) changes in artificially induced CSDs in the postresuscitation period. Male Sprague-Dawley rats were randomized into four groups: 1) CA 90, 2) Control 90, 3) CA 360, and 4) Control 360. Following 8 min of asphyxial CA, animals were resuscitated using adrenaline, ventilation, and chest compressions. Animals were observed for 90 or 360 min, respectively, before a 210-min data collection period. Cortical potentials were recorded through burr holes over the right hemisphere. Animals were intubated and monitored with invasive blood pressure, ECG, and arterial blood gas samples throughout the study. Spontaneous DC shifts occurred in only 1 of the 14 CA animals. In control animals, DC shifts were easy to induce, and their shape was highly uniform, consistent with that of classical CSDs. In CA animals, significantly fewer DC shifts could be induced, and their shape was profoundly altered compared with controls. We observed frequent epileptiform discharges and temporal clusters of activity. Spontaneous CSDs were not a consistent finding in CA animals. Instead, spontaneous epileptiform discharges and temporal cluster of activity were observed, while the shapes of induced DC shifts were profoundly altered compared with controls. © 2017 Wiley Periodicals, Inc.
Assuntos
Encéfalo/fisiopatologia , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Parada Cardíaca/complicações , Animais , Reanimação Cardiopulmonar , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Only one in ten patients survives cardiac arrest (CA), underscoring the need to improve CA management. Isoflurane has shown cardio- and neuroprotective effects in animal models of ischemia-reperfusion injury. Therefore, the beneficial effect of isoflurane should be tested in an experimental CA model. We hypothesize that isoflurane anesthesia improves short-term outcome following resuscitation from CA compared with a subcutaneous fentanyl/fluanisone/midazolam anesthesia. Male Sprague-Dawley rats were randomized to anesthesia with isoflurane (n = 11) or fentanyl/fluanisone/midazolam (n = 11). After 10 min of asphyxial CA, animals were resuscitated by mechanical chest compressions, ventilations, and epinephrine and observed for 30 min. Hemodynamics, including coronary perfusion pressure, systemic O2 consumption, and arterial blood gases, were recorded throughout the study. Plasma samples for endothelin-1 and cathecolamines were drawn before and after CA. Compared with fentanyl/fluanisone/midazolam anesthesia, isoflurane resulted in a shorter time to return of spontaneous circulation (ROSC), less use of epinephrine, increased coronary perfusion pressure during cardiopulmonary resusitation, higher mean arterial pressure post-ROSC, increased plasma levels of endothelin-1, and decreased levels of epinephrine. The choice of anesthesia did not affect ROSC rate or systemic O2 consumption. Isoflurane reduces time to ROSC, increases coronary perfusion pressure, and improves hemodynamic function, all of which are important parameters in CA models.NEW & NOTEWORTHY The preconditioning effect of volatile anesthetics in studies of ischemia-reperfusion injury has been demonstrated in several studies. This study shows the importance of anesthesia in experimental cardiac arrest studies as isoflurane raised coronary perfusion pressure during resuscitation, reduced time to return of spontaneous circulation, and increased arterial blood pressure in the post-cardiac arrest period. These effects on key outcome measures in cardiac arrest research are important in the interpretation of results from animal studies.
Assuntos
Butirofenonas/farmacologia , Fentanila/farmacologia , Parada Cardíaca/terapia , Isoflurano/farmacologia , Midazolam/farmacologia , Anestesia , Animais , Reanimação Cardiopulmonar , Catecolaminas/sangue , Endotelina-1/sangue , Epinefrina/farmacologia , Hemodinâmica , Masculino , Consumo de Oxigênio , Ratos Sprague-DawleyRESUMO
Endothelial activation is pivotal in the development and escalation of sepsis. Central to endothelial activation is the endothelial up-regulation of cellular adhesion molecules (CAMs) including E-selectin, ICAM-1, VCAM-1, and PECAM-1. Shed CAMs are also found in circulating soluble forms (sCAMs). We investigated whether sCAMs can be used as biomarkers for the differentiation between septic and non-septic patients. Furthermore, we investigated lymphocyte and monocyte expression of LFA-1 (CD11a/CD18) and VLA-4 (CD49d/CD29) ligands for ICAM-1 and VCAM-1, respectively. Twenty-one septic and 15 critically ill non-septic patients were included. All patients had an APACHE II score above 13 at ICU admission. Fifteen healthy volunteers served as controls. Flow cytometry was used to estimate levels of sE-selectin, sICAM-1, sVCAM-1, sPECAM-1, and the cellular expression of CD11a and CD49d. Levels of sE-selectin, sICAM-1 and sPECAM-1 were higher in the septic patients compared with the non-septic patients and controls at admission and during the observation period. Lymphocyte and monocyte expression of CD11a and CD49d was suppressed or unaltered in the septic patients compared with the non-septic patients and controls. Levels of sE-selectin, sICAM-1, and sPECAM-1 were able to discriminate between septic and non-septic patients, indicating that sCAMs may be potential diagnostic biomarkers of sepsis.
Assuntos
Biomarcadores/análise , Biomarcadores/sangue , Antígeno CD11a/análise , Moléculas de Adesão Celular/sangue , Integrina alfa4/análise , Monócitos/química , Sepse/diagnóstico , APACHE , Idoso , Estado Terminal , Feminino , Citometria de Fluxo , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sepse/patologiaRESUMO
NEW FINDINGS: What is the central question of this study? The brain response to acute hyponatraemia is usually studied in rodents by intraperitoneal instillation of hypotonic fluids (i.p. model). The i.p. model is described as 'dilutional' and 'syndrome of inappropriate ADH (SIADH)', but the mechanism has not been explored systematically and might affect the brain response. Therefore, in vivo brain and muscle response were studied in pigs. What is the main finding and its importance? The i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution, not dilution. A large reduction in brain sodium is observed, probably because of the specific mechanism causing the hyponatraemia. This is not accounted for in current understanding of the brain response to acute hyponatraemia. Hyponatraemia is common clinically, and if it develops rapidly, brain oedema evolves, and severe morbidity and even death may occur. Experimentally, acute hyponatraemia is most frequently studied in small animal models, in which the hyponatraemia is produced by intraperitoneal instillation of hypotonic fluids (i.p. model). This hyponatraemia model is described as 'dilutional' or 'syndrome of inappropriate ADH (SIADH)', but seminal studies contradict this interpretation. To confront this issue, we developed an i.p. model in a large animal (the pig) and studied water and electrolyte responses in brain, muscle, plasma and urine. We hypothesized that hyponatraemia was induced by simple water dilution, with no change in organ sodium content. Moderate hypotonic hyponatraemia was induced by a single i.v. dose of desmopressin and intraperitoneal instillation of 2.5% glucose. All animals were anaesthetized and intensively monitored. In vivo brain and muscle water was determined by magnetic resonance imaging and related to the plasma sodium concentration. Muscle water content increased less than expected as a result of pure dilution, and muscle sodium content decreased significantly (by 28%). Sodium was redistributed to the peritoneal fluid, resulting in a significantly reduced plasma volume. This shows that the i.p. model induces hypovolaemic hyponatraemia and not dilutional/SIADH hyponatraemia. Brain oedema evolved, but brain sodium content decreased significantly (by 21%). To conclude, the i.p. model induces hypovolaemic hyponatraemia attributable to sodium redistribution and not water dilution. The large reduction in brain sodium is probably attributable to the specific mechanism that causes the hyponatraemia. This is not accounted for in the current understanding of the brain response to acute hyponatraemia.
Assuntos
Líquido Ascítico/metabolismo , Encéfalo/metabolismo , Hiponatremia/metabolismo , Hiponatremia/fisiopatologia , Hipovolemia/metabolismo , Hipovolemia/fisiopatologia , Sódio/metabolismo , Animais , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Eletrólitos , Feminino , Síndrome de Secreção Inadequada de HAD/metabolismo , Síndrome de Secreção Inadequada de HAD/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Músculos/metabolismo , Suínos , Água/metabolismoRESUMO
INTRODUCTION: Long-term psychological consequences of critical illness are receiving more attention in recent years. The aim of our study was to assess the correlation of ICU-delirium and symptoms of posttraumatic stress disorder (PTSD) anxiety and depression after ICU-discharge in a Danish cohort. METHODS: A prospective observational cohort study assessing the incidence of delirium in the ICU. Psychometrics were screened by validated tools in structured telephone interviews after 2 months (n = 297) and 6 months (n = 248) after ICU-discharge. RESULTS: Delirium was detected in 54% of patients in the ICU and symptoms of PTSD in 8% (2 months) and 6% (6 months) after ICU-discharge. Recall of ICU stay was present in 93%. Associations between ICU-delirium and post-discharge PTSD-symptoms were weak and insignificant. Memories of delusions were significantly associated with anxiety after two months. Remaining associations between types of ICU-memories and prevalence of post-discharge symptoms of PTSD, anxiety, and depression were insignificant after adjusting for age. Incidence of ICU-delirium was unaffected by preadmission use of psychotropic drugs. Prevalence of PTSD-symptoms was unaffected by use of antipsychotics and sedation in the ICU. CONCLUSION: ICU-delirium did not increase the risk of PTSD-symptoms at 2 and 6 months after ICU discharge.
Assuntos
Cuidados Críticos , Delírio/complicações , Delírio/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Transtornos de Estresse Pós-Traumáticos/fisiopatologiaRESUMO
OBJECTIVE: Recent studies show that sublingual microcirculation is altered in patients resuscitated from CA. The objective of this study was to investigate whether the cerebral microcirculation is disturbed in the early post-resuscitation period. METHODS: Male Sprague-Dawley rats were randomized to either 10 minutes of CA or uninterrupted circulation, and observed to 120 or 360 minutes after ROSC. At 120 and 360 minutes, cerebral microcirculation was evaluated by SDF microscopy through a craniectomy. Plasma samples were analyzed for endothelial adhesion molecules and inflammatory markers, and brains were fixated for histological analysis. RESULTS: Cerebral microcirculation, evaluated by TVD, PVD, PPV, and MFI did not differ between groups (p > 0.16). Plasma samples drawn 360 minutes after ROSC displayed a significant increase in sE-selectin, sL-selectin, sI-CAM1, IL-1ß, IL-6, IL-10, and elastase compared to controls. In the CA animals, sE-selectin and elastase increased between 120 and 360 minutes after resuscitation (p < 0.007). Histological analysis revealed neuronal death in hippocampus layer CA1 360 min after resuscitation. CONCLUSION: When evaluated by SDF, the cerebral microcirculation appears unaffected in the early post-CA period despite hypotension, systemic inflammation, endothelial activation, and neuronal injury.
Assuntos
Encéfalo , Células Endoteliais , Parada Cardíaca , Mediadores da Inflamação/sangue , Microcirculação , Ressuscitação , Animais , Biomarcadores/sangue , Encéfalo/irrigação sanguínea , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Parada Cardíaca/sangue , Parada Cardíaca/patologia , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
AIM: To explore the challenges and caring activities of spouses of intensive care unit survivors during the first year of patient recovery. BACKGROUND: Every year, millions of people globally are discharged from an intensive care unit after critical illness to continue treatment, care and rehabilitation in general hospital wards, rehabilitation facilities and at home. Consequently, millions of spouses become informal caregivers. Little is known, however, about the concrete challenges spouses face in post-intensive care unit everyday life. DESIGN: Explorative, qualitative grounded theory study. METHODS: Participants were spouses of intensive care unit survivors. The study was undertaken in Denmark in 2009-2010. Data consisted of 35 semi-structured dyad interviews at 3 and 12 months post-intensive care unit discharge, two group interviews with patients and two with spouses. FINDINGS: 'Shifting their role from spouse to caregiver and back' was identified as the core category of the study. The role shifts progressed in a dynamic process involving four elements: (1) committing to caregiving; (2) acquiring caregiving skills; (3) negotiating level of caregiving and (4) gradually leaving the caregiver role. Post-ICU caregiving comprised five patient dimensions: observing, assisting, coaching, advocating and managing activities. CONCLUSIONS: Spouses play a vital and multifaceted role in post-intensive care unit recovery. The findings can inform healthcare professionals in their efforts to prepare intensive care unit patients' families for the time following intensive care unit and hospital discharge. Hospital staff, rehabilitation experts and primary care professionals must acknowledge spouses' important contribution from intensive care unit admission throughout recovery.
Assuntos
Cuidadores , Teoria Fundamentada , Unidades de Terapia Intensiva , Cônjuges , HumanosRESUMO
INTRODUCTION: Coagulopathy associates with poor outcome in sepsis. Mild induced hypothermia has been proposed as treatment in sepsis but it is not known whether this intervention worsens functional coagulopathy. MATERIALS AND METHODS: Interim analysis data from an ongoing randomized controlled trial; The Cooling And Surviving Septic shock (CASS) study. Patients suffering severe sepsis/septic shock are allocated to either mild induced hypothermia (cooling to 32-34°C for 24hours) or control (uncontrolled temperature). TRIAL REGISTRATION: NCT01455116. Thrombelastography (TEG) is performed three times during the first day after study enrollment in all patients. Reaction time (R), maximum amplitude (MA) and patients' characteristics are here reported. RESULTS: One hundred patients (control n=50 and intervention n=50; male n=59; median age 68years) with complete TEG during follow-up were included. At enrollment, 3%, 38%, and 59% had a hypocoagulable, normocoagulable, and hypercoagulable TEG clot strength (MA), respectively. In the hypothermia group, functional coagulopathy improved during the hypothermia phase, measured by R and MA, in patients with hypercoagulation as well as in patients with hypocoagulation (correlation between ΔR and initial R: rho=-0.60, p<0.0001 and correlation between ΔMA and initial MA: rho=-0.50, p=0.0002). Similar results were not observed in the control group neither for R (rho=-0.03, p=0.8247) nor MA (rho=-0.15, p=0.3115). CONCLUSION: Mild induced hypothermia did seem to improve functional coagulopathy in septic patients. This improvement of functional coagulopathy parameters during the hypothermia intervention persisted after rewarming. Randomized trials are warranted to determine whether the positive effect on sepsis-related coagulopathy can be transformed to improved survival.
Assuntos
Transtornos da Coagulação Sanguínea/terapia , Hipotermia Induzida , Sepse/fisiopatologia , Sepse/terapia , Trombofilia/terapia , Idoso , Coagulação Sanguínea , Elasticidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Choque Séptico/fisiopatologia , Temperatura , Tromboelastografia , Resultado do Tratamento , ViscosidadeRESUMO
INTRODUCTION: The combination of Adenosine (A), lidocaine (L) and Mg(2+) (M) (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock. This study evaluates whether ALM also demonstrates organ protective properties in an endotoxemic porcine model. METHODS: Pigs (37 to 42 kg) were randomized into: 1) Control (n = 8) or 2) ALM (n = 8) followed by lipopolysaccharide infusion (1 µg â kg(-1) â h(-1)) for five hours. ALM treatment consisted of 1) a high dose bolus (A (0.82 mg/kg), L (1.76 mg/kg), M (0.92 mg/kg)), 2) one hour continuous infusion (A (300 µg â kg(-1) â min(-1)), L (600 µg â kg(-1) â min(-1)), M (336 µg â kg(-1) â min(-1))) and three hours at a lower dose (A (240 â kg(-1) â min(-1)), L (480 µg â kg(-1) â min(-1)), M (268 µg â kg(-1) â min(-1))); controls received normal saline. Hemodynamic, cardiac, pulmonary, metabolic and renal functions were evaluated. RESULTS: ALM lowered mean arterial pressure (Mean value during infusion period: ALM: 47 (95% confidence interval (CI): 44 to 50) mmHg versus control: 79 (95% CI: 75 to 85) mmHg, P < 0.0001). After cessation of ALM, mean arterial pressure immediately increased (end of study: ALM: 88 (95% CI: 81 to 96) mmHg versus control: 86 (95% CI: 79 to 94) mmHg, P = 0.72). Whole body oxygen consumption was significantly reduced during ALM infusion (ALM: 205 (95% CI: 192 to 217) ml oxygen/min versus control: 231 (95% CI: 219 to 243) ml oxygen/min, P = 0.016). ALM treatment reduced pulmonary injury evaluated by PaO2/FiO2 ratio (ALM: 388 (95% CI: 349 to 427) versus control: 260 (95% CI: 221 to 299), P = 0.0005). ALM infusion led to an increase in heart rate while preserving preload recruitable stroke work. Creatinine clearance was significantly lower during ALM infusion but reversed after cessation of infusion. ALM reduced tumor necrosis factor-α peak levels (ALM 7121 (95% CI: 5069 to 10004) pg/ml versus control 11596 (95% CI: 9083 to 14805) pg/ml, P = 0.02). CONCLUSION: ALM infusion induces a reversible hypotensive and hypometabolic state, attenuates tumor necrosis factor-α levels and improves cardiac and pulmonary function, and led to a transient drop in renal function that was reversed after the treatment was stopped.
Assuntos
Adenosina/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Endotoxemia/tratamento farmacológico , Hipotensão/induzido quimicamente , Lidocaína/administração & dosagem , Magnésio/administração & dosagem , Animais , Modelos Animais de Doenças , Quimioterapia Combinada , Endotoxemia/metabolismo , Feminino , Coração/efeitos dos fármacos , Coração/fisiologia , Hipotensão/metabolismo , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Distribuição Aleatória , Testes de Função Respiratória/métodos , SuínosRESUMO
Guillain-Barré syndrome is the leading cause of acute flaccid paralysis in the industrialized world. Approximately 25% of the patients suffering from Guillain-Barré syndrome develop respiratory failure requiring mechanical ventilation and intensive therapy. We seek answers to when it is optimal to start respiratory supportive therapy and review various complications associated with Guillain-Barré syndrome.
Assuntos
Síndrome de Guillain-Barré/terapia , Cuidados Críticos , Síndrome de Guillain-Barré/complicações , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Humanos , Respiração Artificial , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapiaRESUMO
Sepsis, severe sepsis and septic shock are syndromes. The incidence of sepsis is as high as 35% and with mortality rates in the intensive care unit from 27% to 54% in sepsis and septic shock, respectively. Many new treatments have been tested but only few have been implemented in clinical practise. The treatment of severe sepsis and septic shock is based on the Surviving Sepsis Campaign guidelines developed by an international expert panel. Early diagnosis, optimization of haemodynamics, rapid identification of focus and adequate antibiotic treatment are the most important strategies.
Assuntos
Sepse , Choque Séptico , Antibacterianos/uso terapêutico , Diagnóstico Precoce , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como Assunto , Sepse/diagnóstico , Sepse/tratamento farmacológico , Sepse/terapia , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico , Choque Séptico/terapiaRESUMO
BACKGROUND: The diagnosis of sepsis is challenging and there is an unmet need for sensitive and specific diagnostic and prognostic biomarkers. Following activation of macrophages and monocytes, the haptoglobin-haemoglobin receptor (CD163) and the mannose receptor (MR) are shed into the circulation (sCD163 and sMR). OBJECTIVE: We investigated monocyte expression of CD163 and MR, and levels of sCD163 and sMR in septic and non-septic patients, and in healthy controls. We hypothesised that these receptors are elevated during sepsis and can be used diagnostic and prognostic. METHODS: Twenty-one patients with severe sepsis or septic shock and 15 critically ill non-septic patients were included in this prospective observational study at three ICUs at Aarhus University Hospital and Randers Regional Hospital, Denmark. Fifteen age- and gender-matched healthy volunteers served as controls. Levels of sCD163 and sMR were measured using a sandwich ELISA and monocyte expression of CD163 and MR was evaluated by flow cytometry during the first four days of ICU stay. The diagnostic and prognostic values of the receptors were assessed using AUROC curves. RESULTS: At ICU admission and during the observation period, monocyte expression of CD163 and levels of sCD163 and sMR were significantly higher in septic patients compared with non-septic patients and healthy controls (p<0.01 for all comparisons). Monocytes did not express MR. The diagnostic values estimated by AUROC were 1.00 for sMR, 0.95 for sCD163, 0.87 for CRP, and 0.75 for monocyte-bound CD163. Among the septic patients, monocyte expression of CD163 was higher in non-survivors compared with survivors at ICU admission (pâ=â0.02) and during the observation period (pâ=â0.006). The prognostic value of monocyte-bound CD163 estimated by AUROC at ICU admission was 0.82. CONCLUSION: The macrophage-specific markers CD163, sCD163, and sMR are increased in septic patients. Particularly sMR is a promising new biomarker of sepsis.
Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Estado Terminal , Unidades de Terapia Intensiva , Lectinas Tipo C/metabolismo , Lectinas de Ligação a Manose/metabolismo , Monócitos/metabolismo , Receptores de Superfície Celular/metabolismo , Sepse/metabolismo , Idoso , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Sobrevivência Celular , Demografia , Feminino , Hospitalização , Humanos , Lectinas Tipo C/sangue , Contagem de Leucócitos , Masculino , Receptor de Manose , Lectinas de Ligação a Manose/sangue , Pessoa de Meia-Idade , Monócitos/patologia , Ligação Proteica , Curva ROC , Receptores de Superfície Celular/sangue , Sepse/sangue , SolubilidadeRESUMO
OBJECTIVES: Currently, there is no effective small-volume fluid for traumatic hemorrhagic shock. Our objective was to translate small-volume 7.5% NaCl adenosine, lidocaine, and Mg hypotensive fluid resuscitation from the rat to the pig. DESIGN: Pigs (35-40 kg) were anesthetized and bled to mean arterial pressure of 35-40 mm Hg for 90 minutes, followed by 60 minutes of hypotensive resuscitation and infusion of shed blood. Data were collected continuously. SETTING: University hospital laboratory. SUBJECTS: Female farm-bred pigs. INTERVENTIONS: Pigs were randomly assigned to a single IV bolus of 4 mL/kg 7.5% NaCl + adenosine, lidocaine and Mg (n = 8) or 4 mL/kg 7.5% NaCl (n = 8) at hypotensive resuscitation and 0.9% NaCl ± adenosine and lidocaine at infusion of shed blood. MEASUREMENTS AND MAIN RESULTS: At 60 minutes of hypotensive resuscitation, treatment with 7.5% NaCl + adenosine, lidocaine, and Mg generated significantly higher mean arterial pressure (48 mm Hg [95% CI, 44-52] vs 33 mm Hg [95% CI, 30-36], p < 0.0001), cardiac index (76 mL/min/kg [95% CI, 63-91] vs 47 mL/min/kg [95% CI, 39-57], p = 0.002), and oxygen delivery (7.6 mL O2/min/kg [95% CI, 6.4-9.0] vs 5.2 mL O2/min/kg [95% CI, 4.4-6.2], p = 0.003) when compared with controls. Pigs that received adenosine, lidocaine, and Mg/adenosine and lidocaine also had significantly lower blood lactate (7.1 mM [95% CI, 5.7-8.9] vs 11.3 mM [95% CI, 9.0-14.1], p = 0.004), core body temperature (39.3°C [95% CI, 39.0-39.5] vs 39.7°C [95% CI, 39.4-39.9]), and higher base excess (-5.9 mEq/L [95% CI, -8.0 to -3.8] vs -11.2 mEq/L [95% CI, -13.4 to -9.1]). One control died from cardiovascular collapse. Higher cardiac index in the adenosine, lidocaine, and Mg/adenosine and lidocaine group was due to a two-fold increase in stroke volume. Left ventricular systolic ejection times were significantly higher and inversely related to heart rate in the adenosine, lidocaine, and Mg/adenosine and lidocaine group. Thirty minutes after blood return, whole-body oxygen consumption decreased in pigs that received adenosine, lidocaine, and Mg/adenosine and lidocaine (5.7 mL O2/min/kg [95% CI, 4.7-6.8] to 4.9 mL O2/min/kg [95% CI, 4.2-5.8]), whereas it increased in controls (4.2 mL O2/min/kg [95% CI, 3.5-5.0] to 5.8 mL O2/min/kg [95% CI, 4.9-5.8], p = 0.02). After 180 minutes, pigs in the adenosine, lidocaine, and Mg/adenosine and lidocaine group had three-fold higher urinary output (2.1 mL//kg/hr [95% CI, 1.2-3.8] vs 0.7 mL//kg/hr [95% CI, 0.4-1.2], p = 0.001) and lower plasma creatinine levels. CONCLUSION: Small-volume resuscitation with 7.5% NaCl + adenosine, lidocaine, and Mg/adenosine and lidocaine provided superior cardiovascular, acid-base, metabolic, and renal recoveries following severe hemorrhagic shock in the pig compared with 7.5% NaCl alone.
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Quimioterapia Combinada/métodos , Hidratação/métodos , Hipotensão/tratamento farmacológico , Choque Hemorrágico/tratamento farmacológico , Vasodilatadores/administração & dosagem , Adenosina/administração & dosagem , Animais , Volume Sanguíneo/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Hemoglobina A/análise , Hipotensão/metabolismo , Infusões Intravenosas , Lidocaína/administração & dosagem , Magnésio/administração & dosagem , Consumo de Oxigênio/efeitos dos fármacos , Ratos , Soluções para Reidratação/farmacologia , Choque Hemorrágico/metabolismo , Cloreto de Sódio/administração & dosagem , Volume Sistólico/efeitos dos fármacos , Sus scrofaRESUMO
AIM: The aim of this study was to investigate if an initial ETCO2 value at or below 1.3 kPa can be used as a cut-off value for whether return of spontaneous circulation during pre-hospital cardio-pulmonary resuscitation is achievable or not. MATERIALS AND METHODS: We prospectively registered data according to the Utstein-style template for reporting data from pre-hospital advanced airway management from February 1st 2011 to October 31st 2012. Included were consecutive patients at all ages with pre-hospital cardiac arrest treated by eight anaesthesiologist-staffed pre-hospital critical care teams in the Central Denmark Region. RESULTS: We registered data from 595 cardiac arrest patients; in 60.2% (n=358) of these cases the pre-hospital critical care teams performed pre-hospital advanced airway management beyond bag-mask ventilation. An initial end-tidal CO2 measurement following pre-hospital advanced airway management were available in 75.7% (n=271) of these 358 cases. We identified 22 patients, who had an initial end-tidal CO2 at or below 1.3 kPa. Four of these patients achieved return of spontaneous circulation. CONCLUSION: Our results indicates that an initial end-tidal CO2 at or below 1.3 kPa during pre-hospital CPR should not be used as a cut-off value for the achievability of return of spontaneous circulation.
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Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Parada Cardíaca Extra-Hospitalar/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Circulação Sanguínea , Dióxido de Carbono , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Volume de Ventilação Pulmonar , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: Guidelines recommend that patients with brain trauma with a Glasgow Coma Scale (GCS) score of less than 9 should have an airway established. Hypoxia, hypotension and hypertension as well as hypoventilation and hyperventilation may worsen outcome in these patients. OBJECTIVES: The objectives were to investigate guideline adherence, reasons for nonadherence and the incidences of complications related to prehospital advanced airway management in patients with traumatic brain injury. MATERIALS AND METHODS: We prospectively collected data from eight anaesthesiologist-staffed prehospital critical care teams in the Central Denmark Region according to the Utstein-style template. RESULTS: Among 1081 consecutive prehospital advanced airway management patients, we identified 54 with a traumatic brain injury and an initial GCS score of less than 9. Guideline adherence in terms of airway management was 92.6%. The reasons for nonadherence were the patient's condition, anticipated difficult airway management and short distance to the emergency department. Following rapid sequence intubation (RSI), 11.4% developed oxygen saturation below 90%, 9.1% had a first post-RSI systolic blood pressure below 90 mmHg and 48.9% had a first post-RSI systolic blood pressure below 120 mmHg. The incidence of hypertension following prehospital RSI was 4.5%. The incidence of postendotracheal intubation hyperventilation was as high as 71.1%. CONCLUSION: The guideline adherence was high. The incidences of post-RSI hypoxia and systolic blood pressure below 90 compare with the results reported from other physician-staffed prehospital services. The incidence of systolic blood pressure below 120 as well as that of hyperventilation following prehospital endotracheal intubation in patients with traumatic brain injury call for a change in our current practice.
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Lesões Encefálicas/reabilitação , Serviços Médicos de Emergência/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Escala de Coma de Glasgow , Humanos , Hiperventilação/epidemiologia , Lactente , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Adulto JovemRESUMO
AIMS AND OBJECTIVES: To investigate the effects of delirium in the intensive care unit on health-related quality of life, healthcare dependency and memory after discharge and to explore the association between health-related quality of life and memories, patient diaries and intensive care unit follow-up. BACKGROUND: Up to 83% of intensive care unit patients experience delirium. In addition to increased risk of mortality, morbidity and cognitive impairment, the experience itself is unpleasant. A number of studies have focused on memories associated with delirium, but the association between delirium, memories and health-related quality needs further investigation. DESIGN: We used an observational multicentre design with telephone interviews. METHODS: Adult intensive care unit patients (n = 360) were consecutively recruited and interviewed using the intensive care unit-Memory Tool one week after intensive care unit. Interviews were repeated after two and six months and supplemented with Short Form-36 and the Barthel Index. RESULTS: Delirium was detected in 60% of the patients in our study, and delirious patients had significantly fewer factual memories and more memories of delusion than nondelirious patients up to six months postintensive care unit discharge. Delirium, memories and intensive care unit diaries with follow-up did not affect health-related quality of life and healthcare dependency. Memories of delusions might have an impact on patients assessed as nondelirious. CONCLUSIONS: More than half of the patients in intensive care unit experience delirium, which is associated with fewer factual memories and more memories of delusions. Short Form-36 might not be sensitive to delirium-related outcomes. Future research should include the development of better assessment tools to determine the long-term consequences of intensive care unit delirium. RELEVANCE TO CLINICAL PRACTICE: We recommend regular assessment to prevent, detect and treat delirium. We also recommend an intensive care unit follow-up programme providing an opportunity for postintensive care unit patients, particularly previously delirious patients, to discuss their memories and experiences with intensive care unit professionals.