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1.
N Engl J Med ; 384(24): 2283-2294, 2021 06 17.
Article in English | MEDLINE | ID: covidwho-1275997

ABSTRACT

BACKGROUND: Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. METHODS: In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33°C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, ≥37.8°C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. RESULTS: A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score ≥4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. CONCLUSIONS: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, NCT02908308.).


Subject(s)
Fever/therapy , Hypothermia, Induced , Out-of-Hospital Cardiac Arrest/therapy , Aged , Body Temperature , Cardiopulmonary Resuscitation/methods , Coma/etiology , Coma/therapy , Female , Fever/etiology , Humans , Hypothermia, Induced/adverse effects , Kaplan-Meier Estimate , Male , Middle Aged , Out-of-Hospital Cardiac Arrest/complications , Out-of-Hospital Cardiac Arrest/mortality , Single-Blind Method , Treatment Outcome
2.
Crit Care Med ; 49(9): 1524-1534, 2021 09 01.
Article in English | MEDLINE | ID: covidwho-1191508

ABSTRACT

OBJECTIVES: In patients with coronavirus disease 2019-associated acute respiratory distress syndrome, sedatives and opioids are commonly administered which may lead to increased vulnerability to neurologic dysfunction. We tested the hypothesis that patients with coronavirus disease 2019-associated acute respiratory distress syndrome are at higher risk of in-hospital mortality due to prolonged coma compared with other patients with acute respiratory distress syndrome matched for disease severity. DESIGN: Propensity-matched cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: All mechanically ventilated coronavirus disease 2019 patients between March and May 2020 were identified and matched with patients with acute respiratory distress syndrome of other etiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using clinical data obtained from a hospital registry, we matched 114 coronavirus disease 2019 patients to 228 noncoronavirus disease 2019-related acute respiratory distress syndrome patients based on baseline disease severity. Coma was identified using the Richmond Agitation Sedation Scale less than or equal to -3. Multivariable logistic regression and mediation analyses were used to assess the percentage of comatose days, sedative medications used, and the association between coronavirus disease 2019 and in-hospital mortality. In-hospital mortality (48.3% vs 31.6%, adjusted odds ratio, 2.15; 95% CI, 1.34-3.44; p = 0.002), the percentage of comatose days (66.0% ± 31.3% vs 36.0% ± 36.9%, adjusted difference, 29.35; 95% CI, 21.45-37.24; p < 0.001), and the hypnotic agent dose (51.3% vs 17.1% of maximum hypnotic agent dose given in the cohort; p < 0.001) were higher among patients with coronavirus disease 2019. Brain imaging did not show a higher frequency of structural brain lesions in patients with coronavirus disease 2019 (6.1% vs 7.0%; p = 0.76). Hypnotic agent dose was associated with coma (adjusted coefficient, 0.61; 95% CI, 0.45-0.78; p < 0.001) and mediated (p = 0.001) coma. Coma was associated with in-hospital mortality (adjusted odds ratio, 5.84; 95% CI, 3.58-9.58; p < 0.001) and mediated 59% of in-hospital mortality (p < 0.001). CONCLUSIONS: Compared with matched patients with acute respiratory distress syndrome of other etiology, patients with coronavirus disease 2019 received higher doses of hypnotics, which was associated with prolonged coma and higher mortality.


Subject(s)
COVID-19/drug therapy , Coma/etiology , Hospital Mortality , Hypnotics and Sedatives/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Aged , Analgesics/therapeutic use , Brain/diagnostic imaging , Brain/pathology , COVID-19/complications , COVID-19/mortality , Female , Humans , Hypnotics and Sedatives/adverse effects , Logistic Models , Male , Middle Aged , Neuromuscular Blocking Agents/therapeutic use , Propensity Score , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Retrospective Studies
3.
Neurologia (Engl Ed) ; 36(2): 127-134, 2021 Mar.
Article in English, Spanish | MEDLINE | ID: covidwho-1065502

ABSTRACT

OBJECTIVES: Since the beginning of the COVID-19 pandemic, the Spanish Society of Neurology has run a registry of patients with neurological involvement for the purpose of informing clinical neurologists. Encephalopathy and encephalitis were among the most frequently reported complications. In this study, we analyse the characteristics of these complications. PATIENTS AND METHODS: We conducted a retrospective, descriptive, observational, multicentre study of patients with symptoms compatible with encephalitis or encephalopathy, entered in the Spanish Society of Neurology's COVID-19 Registry from 17 March to 6 June 2020. RESULTS: A total of 232 patients with neurological symptoms were registered, including 51 cases of encephalopathy or encephalitis (21.9%). None of these patients were healthcare professionals. The most frequent syndromes were mild or moderate confusion (33%) and severe encephalopathy or coma (9.8%). The mean time between onset of infection and onset of neurological symptoms was 8.02 days. Lumbar puncture was performed in 60.8% of patients, with positive PCR results for SARS-CoV-2 in only one case. Brain MRI studies were performed in 47% of patients, with alterations detected in 7.8% of these. EEG studies were performed in 41.3% of cases, detecting alterations in 61.9%. CONCLUSIONS: Encephalopathy and encephalitis are among the complications most frequently reported in the registry. More than one-third of patients presented mild or moderate confusional syndrome. The mean time from onset of infection to onset of neurological symptoms was 8 days (up to 24hours earlier in women than in men). EEG was the most sensitive test in these patients, with very few cases presenting alterations in neuroimaging studies. All patients treated with boluses of corticosteroids or immunoglobulins progressed favourably.


Subject(s)
Brain Diseases/etiology , COVID-19/complications , Encephalitis, Viral/etiology , Pandemics , SARS-CoV-2/pathogenicity , Adrenal Cortex Hormones/therapeutic use , Brain Diseases/epidemiology , Brain Diseases/virology , COVID-19/epidemiology , Cognition Disorders/epidemiology , Coma/epidemiology , Coma/etiology , Coma/virology , Comorbidity , Electroencephalography , Encephalitis, Viral/epidemiology , Encephalitis, Viral/virology , Epilepsy/epidemiology , Female , Humans , Hypertension/epidemiology , Immunoglobulins, Intravenous/therapeutic use , Magnetic Resonance Imaging , Male , Neuroimaging , Registries , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/etiology , Retrospective Studies , SARS-CoV-2/isolation & purification , Spain/epidemiology , Stroke/epidemiology
4.
Neurology ; 96(10): e1437-e1442, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1027729

ABSTRACT

OBJECTIVE: We report a case series of patients with prolonged but reversible unconsciousness after coronavirus disease 2019 (COVID-19)-related severe respiratory failure. METHODS: A case series of patients who were admitted to the intensive care unit due to COVID-19-related acute respiratory failure is described. RESULTS: After cessation of sedatives, the described cases all showed a prolonged comatose state. Diagnostic neurologic workup did not show signs of devastating brain injury. The clinical pattern of awakening started with early eye opening without obeying commands and persistent flaccid weakness in all cases. Time between cessation of sedatives to the first moment of being fully responsive with obeying commands ranged from 8 to 31 days. CONCLUSION: Prolonged unconsciousness in patients with severe respiratory failure due to COVID-19 can be fully reversible, warranting a cautious approach for prognostication based on a prolonged state of unconsciousness.


Subject(s)
COVID-19/complications , Coma/etiology , Respiratory Insufficiency/complications , Adult , Aged , Coma/diagnostic imaging , Coma/pathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Respiratory Insufficiency/etiology , Time Factors , Treatment Outcome , White Matter/diagnostic imaging , White Matter/pathology
5.
J Stroke Cerebrovasc Dis ; 30(3): 105609, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1012468

ABSTRACT

The case of a 70-year-old male presenting an ischemic stroke related to COVID-19 infection is described. He was initially admitted to the hospital with respiratory insufficiency syndrome secondary to pneumonia caused by SARS Co2. In the next days, he developed rapid neurological deterioration characterized by drowsiness which progressed to deep coma. D-dimer was elevated. Brain CT scan showed bilateral massive ischemic stroke located in the anterior circulation, CT angiogram showed occlusion in the left internal carotid artery and the right middle cerebral artery. The deterioration of the patient continued and he subsequently died. Large vessel occlusion has been reported in COVID-19 patients, but this clinical presentation is usually unilateral. Cases of bilateral occlusion of large vessels have not been previously reported in COVID-19 patients. This report shows that bilateral massive stroke may occur in COVID-19 cases and it should be suspected in patients who show rapid neurological deterioration without focal deficits.


Subject(s)
Arterial Occlusive Diseases/etiology , COVID-19/complications , Ischemic Stroke/etiology , Aged , Brain/diagnostic imaging , COVID-19/diagnostic imaging , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/etiology , Coma/etiology , Computed Tomography Angiography , Fibrin Fibrinogen Degradation Products/analysis , Humans , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/etiology , Ischemic Stroke/diagnostic imaging , Male , Nervous System Diseases/etiology , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Thrombectomy
6.
Clin Neurophysiol ; 132(1): 202-203, 2021 01.
Article in English | MEDLINE | ID: covidwho-893695
7.
Clin Neurophysiol ; 132(1): 218-225, 2021 01.
Article in English | MEDLINE | ID: covidwho-807009

ABSTRACT

OBJECTIVE: Encephalopathy is a major neurological complication of severe Coronavirus Disease 2019 (COVID-19), but has not been fully defined yet. Further, it remains unclear whether neurological manifestations are primarily due to neurotropism of the virus, or indirect effects, like cerebral hypoxia. METHODS: We analysed the electroencephalograms (EEGs) of 19 consecutive patients with laboratory-confirmed COVID-19, performed at peak disease severity as part of their clinical management. Disease severity, respiratory failure, immune and metabolic dysfunction, sedation status, and neurological examination on the day of the EEG were noted. RESULTS: Severe encephalopathy was confirmed in 13 patients, all with severe COVID-19; 10 remained comatose off sedation, and five of them had alpha coma (AC). Disease severity, sedation, immune and metabolic dysfunction were not different between those with AC and those without. CONCLUSIONS: Severe COVID-19 encephalopathy is a principal cause of persisting coma after sedation withdrawal. The relatively high incidence of the rare AC pattern may reflect direct SARS-CoV-2 neurotropism with a predilection for the brainstem ascending reticular system. SIGNIFICANCE: Systematic early EEG detection of encephalopathy related to severe COVID-19 is important for the acute care and the management of long-term neurological and cognitive sequelae, and may help our better understanding of its pathophysiology.


Subject(s)
Brain Diseases/physiopathology , Brain/physiopathology , COVID-19/physiopathology , Coma/physiopathology , Adult , Aged , Aged, 80 and over , Brain Diseases/etiology , COVID-19/complications , Coma/etiology , Electroencephalography , Female , Humans , Male , Middle Aged , Retrospective Studies
8.
Neurol India ; 68(3): 560-572, 2020.
Article in English | MEDLINE | ID: covidwho-640338

ABSTRACT

COVID-19, in most patients, presents with mild flu-like illness. Elderly patients with comorbidities, like hypertension, diabetes, or lung and cardiac disease, are more likely to have severe disease and deaths. Neurological complications are frequently reported in severely or critically ill patients with comorbidities. In COVID-19, both central and peripheral nervous systems can be affected. The SARS-CoV-2 virus causes the disease COVID-19 and has the potential to invade the brain. The SARS-CoV-2 virus enters the brain either via a hematogenous route or olfactory system. Angiotensin-converting enzyme two receptors, present on endothelial cells of cerebral vessels, are a possible viral entry point. The most severe neurological manifestations, altered sensorium (agitation, delirium, and coma), are because of hypoxic and metabolic abnormalities. Characteristic cytokine storm incites severe metabolic changes and multiple organ failure. Profound coagulopathies may manifest with ischemic or hemorrhagic stroke. Rarely, SARS-CoV-2 virus encephalitis or pictures like acute disseminated encephalomyelitis or acute necrotizing encephalopathy have been reported. Nonspecific headache is a commonly experienced neurological symptom. A new type of headache "personal protection equipment-related headache" has been described. Complete or partial anosmia and ageusia are common peripheral nervous system manifestations. Recently, many cases of Guillain-Barré syndrome in COVID-19 patients have been observed, and a postinfectious immune-mediated inflammatory process was held responsible for this. Guillain-Barré syndrome does respond to intravenous immunoglobulin. Myalgia/fatigue is also common, and elevated creatine kinase levels indicate muscle injury. Most of the reports about neurological complications are currently from China. COVID-19 pandemic is spreading to other parts of the world; the spectrum of neurological complications is likely to widen further.


Subject(s)
Ageusia/physiopathology , Coronavirus Infections/physiopathology , Cytokine Release Syndrome/immunology , Encephalitis/physiopathology , Guillain-Barre Syndrome/physiopathology , Headache/physiopathology , Olfaction Disorders/physiopathology , Pneumonia, Viral/physiopathology , Stroke/physiopathology , Ageusia/etiology , Betacoronavirus , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/etiology , Blood-Brain Barrier , Brain Ischemia/blood , Brain Ischemia/etiology , Brain Ischemia/immunology , Brain Ischemia/physiopathology , COVID-19 , Coma/etiology , Coma/physiopathology , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/immunology , Delirium/etiology , Delirium/physiopathology , Encephalitis/etiology , Encephalitis/immunology , Encephalomyelitis, Acute Disseminated/etiology , Encephalomyelitis, Acute Disseminated/immunology , Encephalomyelitis, Acute Disseminated/physiopathology , Fatigue/etiology , Fatigue/physiopathology , Guillain-Barre Syndrome/etiology , Headache/etiology , Humans , Intracranial Hemorrhages/blood , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/physiopathology , Leukoencephalitis, Acute Hemorrhagic/etiology , Leukoencephalitis, Acute Hemorrhagic/immunology , Leukoencephalitis, Acute Hemorrhagic/physiopathology , Myalgia/etiology , Myalgia/physiopathology , Olfaction Disorders/etiology , Pandemics , Personal Protective Equipment/adverse effects , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/immunology , SARS-CoV-2 , Stroke/blood , Stroke/etiology , Stroke/immunology
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