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1.
Neurology ; 103(3): e209608, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-38991197

RESUMO

OBJECTIVES: Rhythmic and periodic patterns (RPPs) on EEG in patients in a coma after cardiac arrest are associated with a poor neurologic outcome. We characterize RPPs using qEEG in relation to outcomes. METHODS: Post hoc analysis was conducted on 172 patients in a coma after cardiac arrest from the TELSTAR trial, all with RPPs. Quantitative EEG included corrected background continuity index (BCI*), relative discharge power (RDP), discharge frequency, and shape similarity. Neurologic outcomes at 3 months after arrest were categorized as poor (CPC = 3-5) or good (CPC = 1-2). RESULTS: A total of 16 patients (9.3%) had a good outcome. Patients with good outcomes showed later RPP onset (28.5 vs 20.1 hours after arrest, p < 0.05) and higher background continuity at RPP onset (BCI* = 0.83 vs BCI* = 0.59, p < 0.05). BCI* <0.45 at RPP onset, maximum BCI* <0.76, RDP >0.47, or shape similarity >0.75 were consistently associated with poor outcomes, identifying 36%, 22%, 40%, or 24% of patients with poor outcomes, respectively. In patients meeting both BCI* >0.44 at RPP onset and BCI* >0.75 within 72 hours, the probability of good outcomes doubled to 18%. DISCUSSION: Sufficient EEG background continuity before and during RPPs is crucial for meaningful recovery. Background continuity, discharge power, and shape similarity can help select patients with relevant chances of recovery and may guide treatment. TRIAL REGISTRATION INFORMATION: February 4, 2014, ClinicalTrial.gov, NCT02056236.


Assuntos
Coma , Eletroencefalografia , Parada Cardíaca , Humanos , Coma/fisiopatologia , Coma/etiologia , Eletroencefalografia/métodos , Masculino , Feminino , Parada Cardíaca/complicações , Parada Cardíaca/fisiopatologia , Pessoa de Meia-Idade , Idoso
2.
Trials ; 25(1): 502, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044295

RESUMO

BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.


Assuntos
Coma , Hipotermia Induzida , Estudos Multicêntricos como Assunto , Parada Cardíaca Extra-Hospitalar , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Hipotermia Induzida/métodos , Hipotermia Induzida/efeitos adversos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Coma/terapia , Coma/etiologia , Coma/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Recuperação de Função Fisiológica , Neuroproteção , Estados Unidos , Pesquisa Comparativa da Efetividade
4.
Turk J Pediatr ; 66(3): 369-377, 2024 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-39024595

RESUMO

BACKGROUND: Myxedema coma is a rare, but life-threatening endocrinological emergency. Myxedema is characterized by altered mental status, and is accompanied by hypotension, bradycardia, hypothermia, bradypnea, hyporeflexia, hyponatremia, and hypoglycemia, all stemming from reduced metabolism due to severe hypothyroidism. Additionally, patients may exhibit signs of low cardiac output, edema in the extremities, peripheral circulatory disturbances, shock, and the development of pericardial and pleural effusions, ultimately leading to confusion and coma. We present a successfully treated case of severe myxedema coma with recurrent pericardial effusion and hypotensive shock. This case is characterized by an unusual clinical presentation and required a distinct treatment strategy highlighting its exceptional rarity. CASE: A 2-year-old boy with Down syndrome presented with recurrent pericardial effusion attributed to medication non-adherence. The critically-ill patient, experiencing a severe cardiogenic shock required mechanical ventilation and inotropic infusions in the pediatric intensive care unit. Elevated thyroid stimulating hormone (TSH), and low free T4 (fT4) and free T3 (fT3) levels prompted consideration of myxedema coma. Upon reviewing the patient's medical history, it was ascertained that he had an ongoing diagnosis of primary hypothyroidism, and exhibited non-adherence to the prescribed treatment regimen and failed to attend scheduled outpatient clinic appointments for follow-up assessments. The treatment plan, devised by the pediatric endocrinology team, included the peroral administration of L-thyroxine (L-T4) at a dose of 50 micrograms per day. After beginning regular oral L-T4 treatment, a gradual improvement in the patient's condition was observed. Notably, by the 15th day of oral therapy, the patient had made a full recovery. Contrary to the recommended intravenous treatment for myxedema coma, this patient was successfully treated with oral levothyroxine, due to the unavailability of the parenteral form in Türkiye. CONCLUSIONS: This case report presents an instance of non-adherence to L-T4 therapy, which subsequently progressed to severe myxedema coma. Changes in neurologic status and hemodynamic instability in a patient with a history of hypothyroidism should raise the concern of nonadherence and, though rare, myxedema coma should be in the differential diagnosis.


Assuntos
Coma , Síndrome de Down , Mixedema , Derrame Pericárdico , Tiroxina , Humanos , Masculino , Mixedema/tratamento farmacológico , Mixedema/diagnóstico , Mixedema/complicações , Tiroxina/uso terapêutico , Tiroxina/administração & dosagem , Coma/etiologia , Coma/tratamento farmacológico , Pré-Escolar , Derrame Pericárdico/tratamento farmacológico , Derrame Pericárdico/etiologia , Derrame Pericárdico/diagnóstico , Síndrome de Down/complicações , Adesão à Medicação , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/complicações
5.
J Vis Exp ; (209)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39037252

RESUMO

Coma caused by cerebral ischemia is the most serious complication of cerebral ischemia. Four-vessel occlusion can establish a cerebral ischemic coma model for disease research and drug development. However, the commonly used four-vessel occlusion method mainly involves inserting an electrocoagulation pen into the bilateral pterygoid foramen of the first cervical vertebra behind the neck to electrocoagulate the vertebral arteries. This process carries the risk of incomplete electrocoagulation, bleeding, and damage to the brainstem and spinal cord. Twenty-four hours after surgery, re-anesthetized rats undergo carotid artery ligation in front of the neck. Two surgeries expose the rats to a higher risk of infection and increase the experimental period. In this study, during a single surgical procedure, an anterior cervical incision was used to locate the key site where the vertebral artery penetrates the first cervical vertebra. The bilateral vertebral arteries were electrocauterized under visual conditions, while the bilateral common carotid arteries were separated to place loose knots. When the rats showed consciousness of the inversion reaction, the bilateral common carotid arteries were quickly ligated to induce ischemic coma. This method can avoid the risk of infection caused by two surgical operations and is easy to perform with a high success rate, providing a useful reference for relevant practitioners.


Assuntos
Isquemia Encefálica , Coma , Modelos Animais de Doenças , Artéria Vertebral , Animais , Ratos , Coma/etiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/cirurgia , Masculino , Artéria Vertebral/cirurgia , Ratos Sprague-Dawley , Artéria Carótida Primitiva/cirurgia , Eletrocoagulação/métodos
6.
Medicine (Baltimore) ; 103(26): e38773, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941367

RESUMO

Elevated red blood cell distribution width (RDW) can be associated with disease severity. However, studies on RDW for the prognosis of elderly patients with non-traumatic coma (NTC) are lacking. This study aims to examine the relationship between RDW and outcomes in elderly patients with NTC. This observational cohort study included elderly patients (aged ≥ 65 years) with NTC between January 2022 and December 2022. We measured RDW upon patient arrival at the emergency department (ED). We conducted a multivariable analysis using logistic regression of relevant covariates to predict in-hospital mortality. Survival curves based on 30-day mortality were designed using the Kaplan-Meier method. The primary outcome was in-hospital mortality, and the secondary outcome was 30-day mortality. A total of 689 patients were included in the study, and in-hospital mortality was 29.6% (n = 204). Our results found that the RDWs of non-survivors were significantly greater than those of survivors (14.6% vs 13.6%). Multivariable analysis showed that RDWs at ED arrival were independently associated with in-hospital mortality (odds ratio, 1.126; 95% confidence interval, 1.047-1.212; P < .001). The Kaplan-Meier curve indicated that the survival probability of patients with a low RDW was greater than those with a high RDW. Having a high RDW at ED arrival was associated with in-hospital mortality in elderly patients with NTC.


Assuntos
Coma , Índices de Eritrócitos , Mortalidade Hospitalar , Humanos , Idoso , Feminino , Masculino , Coma/mortalidade , Coma/sangue , Idoso de 80 Anos ou mais , Prognóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Estimativa de Kaplan-Meier , Estudos de Coortes
7.
Crit Care Explor ; 6(7): e1101, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38912722

RESUMO

OBJECTIVES: Accurate classification of disorders of consciousness (DoC) is key in developing rehabilitation plans after brain injury. The Coma Recovery Scale-Revised (CRS-R) is a sensitive measure of consciousness validated in the rehabilitation phase of care. We tested the feasibility, safety, and impact of CRS-R-guided rehabilitation in the ICU for patients with DoC after acute hemorrhagic stroke. DESIGN: Retrospective cohort study. SETTING: This single-center study was conducted in the neurocritical care unit at the University of Maryland Medical Center. PATIENTS: We analyzed records from consecutive patients with subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH), who underwent serial CRS-R assessments during ICU admission from April 1, 2018, to December 31, 2021, where CRS-R less than 8 is vegetative state/unresponsive wakefulness syndrome (VS/UWS); CRS-R greater than or equal to 8 is a minimally conscious state (MCS). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included adverse events during CRS-R evaluations and associations between CRS-R and discharge disposition, therapy-based function, and mobility. We examined the utility of CRS-R compared with other therapist clinical assessment tools in predicting discharge disposition. Seventy-six patients (22 SAH, 54 ICH, median age = 59, 50% female) underwent 276 CRS-R sessions without adverse events. Discharge to acute rehabilitation occurred in 4.4% versus 41.9% of patients with a final CRS-R less than 8 and CRS-R greater than or equal to 8, respectively (odds ratio [OR] 13.4; 95% CI, 2.7-66.1; p < 0.001). Patients with MCS on final CRS-R completed more therapy sessions during hospitalization and had improved mobility and functional performance. Compared with other therapy assessment tools, the CRS-R had the best performance in predicting discharge disposition (area under the curve: 0.83; 95% CI, 0.72-0.94; p < 0.0001). CONCLUSIONS: Early neurorehabilitation guided by CRS-R appears to be feasible and safe in the ICU following hemorrhagic stroke complicated by DoC and may enhance access to inpatient rehabilitation, with the potential for lasting benefit on recovery. Further research is needed to assess generalizability and understand the impact on long-term outcomes.


Assuntos
Transtornos da Consciência , Estado Terminal , Recuperação de Função Fisiológica , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Transtornos da Consciência/reabilitação , Transtornos da Consciência/diagnóstico , Estudos de Viabilidade , Coma/diagnóstico , Coma/etiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/reabilitação , Estudos de Coortes , Unidades de Terapia Intensiva
8.
Circ Heart Fail ; 17(6): e011437, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38847097

RESUMO

BACKGROUND: To assess the effect of targeting higher or lower blood pressure during postresucitation intensive care among comatose patients with out-of-hospital cardiac arrest with a history of heart failure. METHODS: The BOX trial (Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest) was a randomized, controlled, double-blinded, multicenter study comparing titration of vasopressors toward a mean arterial pressure (MAP) of 63 versus 77 mm Hg during postresuscitation intensive care. Patients with a history of heart failure were included in this substudy. Pulmonary artery catheters were inserted shortly after admission. History of heart failure was assessed through chart review of all included patients. The primary outcome was cardiac index during the first 72 hours. Secondary outcomes were left ventricular ejection fraction, heart rate, stroke volume, renal replacement therapy and all-cause mortality at 365 days. RESULTS: A total of 134 patients (17% of the BOX cohort) had a history of heart failure (patients with left ventricular ejection fraction, ≤40%: 103 [77%]) of which 71 (53%) were allocated to a MAP of 77 mm Hg. Cardiac index at intensive care unit arrival was 1.77±0.11 L/min·m-2 in the MAP63-group and 1.78±0.17 L/min·m-2 in the MAP77, P=0.92. During the next 72 hours, the mean difference was 0.15 (95% CI, -0.04 to 0.35) L/min·m-2; Pgroup=0.22. Left ventricular ejection fraction and stroke volume was similar between the groups. Patients allocated to MAP77 had significantly elevated heart rate (mean difference 6 [1-12] beats/min, Pgroup=0.03). Vasopressor usage was also significantly increased (P=0.006). At 365 days, 69 (51%) of the patients had died. The adjusted hazard ratio for 365 day mortality was 1.38 (0.84-2.27), P=0.20 and adjusted odds ratio for renal replacement therapy was 2.73 (0.84-8.89; P=0.09). CONCLUSIONS: In resuscitated patients with out-of-hospital cardiac arrest with a history of heart failure, allocation to a higher blood pressure target resulted in significantly increased heart rate in the higher blood pressure-target group. However, no certain differences was found for cardiac index, left ventricular ejection fraction or stroke volume. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03141099.


Assuntos
Insuficiência Cardíaca , Parada Cardíaca Extra-Hospitalar , Volume Sistólico , Humanos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/mortalidade , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Método Duplo-Cego , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/fisiopatologia , Parada Cardíaca Extra-Hospitalar/mortalidade , Resultado do Tratamento , Função Ventricular Esquerda/fisiologia , Vasoconstritores/uso terapêutico , Pressão Arterial , Fatores de Tempo , Pressão Sanguínea/fisiologia , Reanimação Cardiopulmonar/métodos , Coma/fisiopatologia , Coma/terapia , Coma/etiologia , Coma/mortalidade
10.
PLoS One ; 19(6): e0305771, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917136

RESUMO

Research on prognostic factors for good outcomes in out-of-hospital cardiac arrest (OHCA) survivors is lacking. We assessed whether normal levels of normal neuron-specific enolase (NSE) value would be useful for predicting good neurological outcomes in comatose OHCA survivors treated with targeted temperature management (TTM). This registry-based observational study with consecutive adult (≥18 years) OHCA survivors with TTM who underwent NSE measurement 48 hours after cardiac arrest was conducted from October 2015 to November 2022. Normal NSE values defined as the upper limit of the normal range by the manufacturer (NSE <16.3 µg/L) and guideline-suggested (NSE < 60 µg/L) were examined for good neurologic outcomes, defined as Cerebral Performance Categories ≤2, at 6 months post-survival. Among 226 OHCA survivors with TTM, 200 patients who underwent NSE measurement were enrolled. The manufacturer-suggested normal NSE values (<16.3 µg/L) had a specificity of 99.17% for good neurological outcomes with a very low sensitivity of 12.66%. NSE <60 µg/L predicted good outcomes with a sensitivity of 87.34% and specificity of 72.73%. However, excluding 14 poor-outcome patients who died from multi-organ dysfunction excluding hypoxic brain injury, the sensitivity and specificity of normal NSE values were 12.66% and 99.07% of NSE < 16.3 µg/L, and 87.34% and 82.24% of NSE < 60 µg/L. The manufacturer-suggested normal NSE had high specificity with low sensitivity, but the guideline-suggested normal NSE value had a comparatively low specificity for good outcome prediction in OHCA survivors. Our data demonstrate normal NSE levels can be useful as a tool for multimodal appropriation of good outcome prediction.


Assuntos
Coma , Parada Cardíaca Extra-Hospitalar , Fosfopiruvato Hidratase , Humanos , Fosfopiruvato Hidratase/sangue , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Coma/etiologia , Idoso , Sobreviventes , Prognóstico , Hipotermia Induzida , Adulto
11.
Crit Care ; 28(1): 162, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741134

RESUMO

BACKGROUND: The effect of the periurethral cleansing range on catheter-associated urinary tract infection (CAUTI) occurrence remains unknown. The purpose of this study was to evaluate the efficacy of expanded periurethral cleansing for reducing CAUTI in comatose patients. METHODS: In this randomized controlled trial, eligible patients in our hospital were enrolled and allocated randomly to the experimental group (expanded periurethral cleansing protocol; n = 225) or the control group (usual periurethral cleansing protocol; n = 221). The incidence of CAUTI on days 3, 7, and 10 after catheter insertion were compared, and the pathogen results and influencing factors were analyzed. RESULTS: The incidences of CAUTI in the experimental and control groups on days 3, 7, and 10 were (5/225, 2.22% vs. 7/221, 3.17%, P = 0.54), (12/225, 5.33% vs. 18/221, 8.14%, P = 0.24), and (23/225, 10.22% vs. 47/221, 21.27%, P = 0.001), respectively; Escherichia coli and Candida albicans were the most common species in the two groups. The incidences of bacterial CAUTI and fungal CAUTI in the two groups were 11/225, 4.89% vs. 24/221, 10.86%, P = 0.02) and (10/225, 4.44% vs. 14/221, 6.33%, P = 0.38), respectively. The incidences of polymicrobial CAUTI in the two groups were 2/225 (0.89%) and 9/221 (4.07%), respectively (P = 0.03). The percentages of CAUTI-positive females in the two groups were 9.85% (13/132) and 29.52% (31/105), respectively (P < 0.05). The proportion of CAUTI-positive patients with diabetes in the experimental and control groups was 17.72% (14/79), which was lower than the 40.85% (29/71) in the control group (P < 0.05). CONCLUSION: Expanded periurethral cleansing could reduce the incidence of CAUTI, especially those caused by bacteria and multiple pathogens, in comatose patients with short-term catheterization (≤ 10 days). Female patients and patients with diabetes benefit more from the expanded periurethral cleansing protocol for reducing CAUTI.


Assuntos
Infecções Relacionadas a Cateter , Coma , Infecções Urinárias , Humanos , Feminino , Infecções Urinárias/prevenção & controle , Infecções Urinárias/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Adulto , Idoso , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/métodos , Uretra
13.
Neuron ; 112(10): 1595-1610, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754372

RESUMO

Recovery of consciousness after coma remains one of the most challenging areas for accurate diagnosis and effective therapeutic engagement in the clinical neurosciences. Recovery depends on preservation of neuronal integrity and evolving changes in network function that re-establish environmental responsiveness. It typically occurs in defined steps: it begins with eye opening and unresponsiveness in a vegetative state, then limited recovery of responsiveness characterizes the minimally conscious state, and this is followed by recovery of reliable communication. This review considers several points for novel interventions, for example, in persons with cognitive motor dissociation in whom a hidden cognitive reserve is revealed. Circuit mechanisms underlying restoration of behavioral responsiveness and communication are discussed. An emerging theme is the possibility to rescue latent capacities in partially damaged human networks across time. These opportunities should be exploited for therapeutic engagement to achieve individualized solutions for restoration of communication and environmental interaction across varying levels of recovery.


Assuntos
Coma , Recuperação de Função Fisiológica , Humanos , Coma/fisiopatologia , Coma/terapia , Recuperação de Função Fisiológica/fisiologia , Estado de Consciência/fisiologia , Estado Vegetativo Persistente/fisiopatologia , Estado Vegetativo Persistente/reabilitação
14.
Sci Rep ; 14(1): 11738, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38778074

RESUMO

Recent preclinical studies demonstrate a direct pathological role for the interleukin-6 (IL-6) pathway in mediating structural and functional delirium-like phenotypes in animal models of acute lung injury. Tocilizumab, an IL-6 pathway inhibitor, has shown reduced duration of ventilator dependency and mortality in critically ill patients with COVID-19. In this study, we test the hypothesis that tocilizumab is associated with reduced delirium/coma prevalence in critically ill patients with COVID-19. 253 patients were included in the study cohort, 69 in the tocilizumab group and 184 in the historical control group who did not receive tocilizumab. Delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) with a positive score indicating delirium. Coma was defined as a Richmond Agitation-Sedation Scale score of - 4 or - 5. Tocilizumab was associated with significantly greater number of days alive without delirium/coma (tocilizumab [7 days (IQR: 3-9 days)] vs control [3 days (IQR: 1-8 days)]; p < 0.001). These results remained significant after adjusting for age, sex, sepsis, Charlson Comorbidity Index, Sequential Organ Failure Assessment score, and median daily dose of analgesics/sedatives ( ß ^ = 0.671, p = 0.010). There were no significant differences in mortality ( ß ^ = - 0.204, p = 0.561), ventilator duration ( ß ^ = 0.016, p = 0.956), and ICU or hospital length of stay ( ß ^ = - 0.134, p = 0.603; ß ^ = 0.003, p = 0.991, respectively). Tocilizumab use was associated with significantly increased number of days without delirium/coma. Confirmation of these findings in randomized prospective studies may inform a novel paradigm of pharmacological amelioration of delirium/coma during critical illness.


Assuntos
Anticorpos Monoclonais Humanizados , COVID-19 , Coma , Estado Terminal , Delírio , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Delírio/tratamento farmacológico , Masculino , Feminino , COVID-19/complicações , COVID-19/mortalidade , Pessoa de Meia-Idade , Coma/etiologia , Coma/tratamento farmacológico , Idoso , Tratamento Farmacológico da COVID-19 , Unidades de Terapia Intensiva , SARS-CoV-2/isolamento & purificação , Interleucina-6
15.
JAMA Neurol ; 81(6): 603-610, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709502

RESUMO

Importance: Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. Objective: To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. Design, Setting, and Participants: A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria. Interventions: Patients were randomized to receive intravenous acyl-ghrelin, 600 µg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care. Main Outcomes and Measures: Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3. Results: A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] µg/L vs 56 [13] µg/L; P = .04) and on day 3 (28 [6] µg/L vs 52 [14] µg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08). Conclusions and Relevance: In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence. Trial Registration: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.


Assuntos
Coma , Grelina , Fármacos Neuroprotetores , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Grelina/uso terapêutico , Método Duplo-Cego , Idoso , Coma/etiologia , Fármacos Neuroprotetores/uso terapêutico , Neuroproteção/fisiologia , Parada Cardíaca/complicações , Parada Cardíaca Extra-Hospitalar/complicações
16.
Med Sci Monit ; 30: e943802, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38741355

RESUMO

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.


Assuntos
Córtex Cerebral , Coma , Estado de Consciência , Imagem de Tensor de Difusão , Hipóxia-Isquemia Encefálica , Tálamo , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Tálamo/fisiopatologia , Tálamo/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/fisiopatologia , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Adulto , Estado de Consciência/fisiologia , Imagem de Tensor de Difusão/métodos , Córtex Cerebral/fisiopatologia , Córtex Cerebral/diagnóstico por imagem , Estudos Retrospectivos , Coma/fisiopatologia , Coma/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagem , Transtornos da Consciência/fisiopatologia , Transtornos da Consciência/diagnóstico por imagem , Idoso
17.
Complement Ther Med ; 82: 103046, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38704101

RESUMO

BACKGROUND: Despite being widely applied in clinical practice, the wake-promoting effect of acupuncture in poststroke coma patients remains controversial. OBJECTIVE: This study aimed to evaluate the efficacy of acupuncture for the treatment of poststroke coma. METHODS: Randomized controlled trials (RCTs) of acupuncture for treating poststroke coma were identified in PubMed, Cochrane Library, EMBASE, CNKI, WanFang and VIP up to 25 November 2023. The main outcomes were Glasgow Coma Scale (GCS) score, National Institute of Health Stroke Scale (NIHSS) score, awakening ratio and clinically effective ratio. Stata 17 and Review Manager 5.4 software were used for mate analysis. RESULTS: A total of 34 RCTs involving 2757 patients were included. GCS (WMD = 1.78; 95% CI: 1.35 to 2.21) and NIHSS score (WMD = -2.84; 95% CI: -3.84 to -1.84) were significantly increased in acupuncture group compared with control group. Acupuncture combined with routine treatment may be better than routine treatment in improving the awakening ratio (RR= 1.65; 95% CI: 1.24 to 2.91) and the clinically effective ratio (RR= 1.20; 95% CI: 1.13 to 1.27). Some methodological flaws were identified in the included studies, including non-implementation of blinding, inappropriate disease assessment and heterogeneous interventions. CONCLUSIONS: The existing evidence suggests that acupuncture combined with conventional treatment may be an effective treatment for poststroke coma patients. In the meantime, more high-quality RCTs are needed to demonstrate these findings due to methodological weaknesses like randomization, blinding, heterogeneous interventions and long-term follow-up.


Assuntos
Terapia por Acupuntura , Coma , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral , Humanos , Terapia por Acupuntura/métodos , Coma/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Escala de Coma de Glasgow
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