[Differential Diagnosis and Management of Disturbance of Consciousness:Approach to Comatose Patients].

Disorders of consciousness are among the most common symptoms in neurosurgery. A coma is an acute dysfunction of the nervous system that governs arousal and awareness and represents a medical emergency. Prompt evaluation and treatment of comas are fundamental in clinical practice. The first step is stabilizing the airway, breathing, and circulation while protecting the cervical spine to prevent secondary neurological injury. Subsequently, a focused neurological examination is performed. The level of consciousness, brainstem reflexes, respiratory patterns, motor responses, and muscle tone should be evaluated. Any asymmetry should be carefully considered. Acute disturbances of consciousness primarily impair arousal. The Japan and Glasgow Coma Scales are the most commonly used. The Emergency Coma Scale was designed by incorporating the advantages of each. The Full Outline of UnResponsiveness score incorporates brainstem reflexes and breathing patterns. Clinicians must have an organized approach to detect remediable causes, prevent neurological injury, and determine a hierarchical course of diagnostic testing, treatments, and neuromonitoring.

Association Between Procalcitonin Level at 72 Hours After Cardiac Arrest and Neurological Outcomes in Cardiac Arrest Survivors.

The association between procalcitonin (PCT) level measured 72 hours after cardiac arrest (CA) and neurological outcomes is unknown. We aimed to examine the association of serial PCT levels up to 72 hours with neurological outcomes in patients who underwent targeted temperature management (TTM) after CA. This retrospective observational study included adult comatose patients with CA undergoing TTM (33℃ for 24 hours) at the Chonnam National University Hospital in Gwangju, Korea, between January 2018 and December 2020. PCT levels were measured at admission and at 24, 48, and 72 hours after CA. The presence of early-onset infections (within 7 days after CA) was confirmed by reviewing clinical, radiological, and microbiological data. The primary outcome was poor neurological outcomes at 6 months and was defined by cerebral performance category 3-5. Among the CA survivors, 118 were included and 67 (56.8%) had poor neurological outcomes. The PCT level at 72 hours in the poor outcome group (3.01 [0.88-12.71]) was higher than that in good outcome group (0.56 [0.18-1.32]). The multivariate analysis revealed that the PCT level at 72 hours (adjusted odds ratio 1.241; 95% confidence interval, 1.059-1.455) was independently associated with poor neurological outcomes, showed good performance for poor outcomes (area under the receiver operating characteristic curve of 0.823), and was not associated with early-onset infections. The PCT level at 72 hours after CA can be helpful in predicting prognosis, and it did not correlate with early-onset infections in the study.

MicroRNA alteration in cerebrospinal fluid from comatose patients with traumatic brain injury after right median nerve stimulation.

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.

SSEP amplitude accurately predicts both good and poor neurological outcome early after cardiac arrest; a post-hoc analysis of the ProNeCA multicentre study.

AIM: To assess if, in comatose resuscitated patients, the amplitude of the N20 wave (N20amp) of somatosensory evoked potentials (SSEP) can predict 6-months neurological outcome. SETTING: Multicentre study in 13 Italian intensive care units. METHODS: The N20amp in microvolts (µV) was measured at 12 h, 24 h, and 72 h from cardiac arrest, along with pupillary reflex (PLR) and a 30-min EEG classified according to the ACNS terminology. Sensitivity and false positive rate (FPR) of N20amp alone or in combination were calculated. RESULTS: 403 patients (age 69[58-68] years) were included. At 12 h, an N20amp >3 µV predicted good neurological outcome (Cerebral Performance Categories [CPC] 1-2) with 61[50-72]% sensitivity and 11[6-18]% FPR. Combining it with a benign (continuous or nearly continuous) EEG increased sensitivity to 91[82-96]%. For poor outcome (CPC 3-5), an N20Amp ≤0.38 µV, ≤0.73 µV and ≤1.01 µV at 12 h, 24 h, and 72 h, respectively, had 0% FPR with sensitivity ranging from 61[51-69]% and 82[76-88]%. Sensitivity was higher than that of a bilaterally absent N20 at all time points. At 12 h and 24 h, a highly malignant (suppression or burst-suppression) EEG and bilaterally absent PLR achieved 0% FPR only when combined with SSEP. A combination of all three predictors yielded a 0[0-4]% FPR, with maximum sensitivity of 44[36-53]%. CONCLUSION: At 12 h from arrest, a high N20Amp predicts good outcome with high sensitivity, especially when combined with benign EEG. At 12 h and 24 h from arrest a low-voltage N20amp has a high sensitivity and is more specific than EEG or PLR for predicting poor outcome.

Does a combination of ≥2 abnormal tests vs. the ERC-ESICM stepwise algorithm improve prediction of poor neurological outcome after cardiac arrest? A post-hoc analysis of the ProNeCA multicentre study.

BACKGROUND: Bilaterally absent pupillary light reflexes (PLR) or N20 waves of short-latency evoked potentials (SSEPs) are recommended by the 2015 ERC-ESICM guidelines as robust, first-line predictors of poor neurological outcome after cardiac arrest. However, recent evidence shows that the false positive rates (FPRs) of these tests may be higher than previously reported. We investigated if testing accuracy is improved when combining PLR/SSEPs with malignant electroencephalogram (EEG), oedema on brain computed tomography (CT), or early status myoclonus (SM). METHODS: Post-hoc analysis of ProNeCA multicentre prognostication study. We compared the prognostic accuracy of the ERC-ESICM prognostication strategy vs. that of a new strategy combining ≥2 abnormal results from any of PLR, SSEPs, EEG, CT and SM. We also investigated if using alternative classifications for abnormal SSEPs (absent-pathological vs. bilaterally-absent N20) or malignant EEG (ACNS-defined suppression or burst-suppression vs. unreactive burst-suppression or status epilepticus) improved test sensitivity. RESULTS: We assessed 210 adult comatose resuscitated patients of whom 164 (78%) had poor neurological outcome (CPC 3-5) at six months. FPRs and sensitivities of the ≥2 abnormal test strategy vs. the ERC-ESICM algorithm were 0[0-8]% vs. 7 [1-18]% and 49[41-57]% vs. 63[56-71]%, respectively (p < .0001). Using alternative SSEP/EEG definitions increased the number of patients with ≥2 concordant test results and the sensitivity of both strategies (67[59-74]% and 54[46-61]% respectively), with no loss of specificity. CONCLUSIONS: In comatose resuscitated patients, a prognostication strategy combining ≥2 among PLR, SSEPs, EEG, CT and SM was more specific than the 2015 ERC-ESICM prognostication algorithm for predicting 6-month poor neurological outcome.

Association of Initial Illness Severity and Outcomes After Cardiac Arrest With Targeted Temperature Management at 36 °C or 33 °C.

Importance: It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. Objective: To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. Design, Setting, and Participants: This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. Exposure: TTM at 36 °C or 33 °C. Main Outcomes and Measures: Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. Results: Among 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, -13.8%; 95% CI, -24.4% to -3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. Conclusions and Relevance: In this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.

Disorders of Consciousness: Practical Management in an Emergency Room

Lowering of the level of consciousness is a very common presentation at the emergency room, often without any history that helps finding an etiology. This emergency requires quick empirical measures to reduce neuronal mortality, with additional protection against sequelae. According to the Advanced Cardiac Life Support (ACLS) guidelines, there are current emergency neurological support protocols, such as the Emergency Neurological Life Support (ENLS) created by the Neurocritical Care Society. The present paper shows how to approach unconscious patients, highlighting possible etiologies and proposed treatments.

Trastornos prolongados de conciencia postinjuria cerebral aguda / Prolonged disorders of consciousness after an acute brain injury

Only a fraction of patients in coma secondary to a primary acute brain injury develop a vegetative state (VS). At least 20% of patients show late transitions to a minimally conscious states (MCS). They are particularly common in young adults with traumatic brain injury. The main problems faced by clinicians are the diagnostic accuracy of VS and MCS as well as the usefulness of sophisticated paraclinical investigations. Specific therapies are of limited effectiveness. This population is vulnerable to misdiagnosis and limited access to medical care and rehabilitation, thus generating ethical problems.

Real and illusory perceptions of patients in induced coma / Percepciones reales e ilusorias de pacientes en coma inducido / Percepções reais e ilusórias de pacientes em coma induzido

ABSTRACT Objective: To identify, in the scientific literature, real and illusory perceptions of adult patients in induced coma. Methods: This is an integrative review of 15 primary studies from the Medline, Web of Science, LILACS, CINAHL and SCOPUS databases. Results: The main memories reported after induced coma were thirst, cold, and pain. In some studies, patients reported they were unable to tell whether they were awake or dreaming, whether it was real or unreal. Satisfactory memories were reported by patients related to the care received and the use of bedside journals. Conclusion: Evidence showed a number of studies aiming to identify delirium, but without a focus on analyzing real or illusory perceptions of patients after induced coma. Thus, this integrative review identified scientific evidence of memories related to perceptions of sedated patients in the intensive care unit.

RESUMEN Objetivo: Identificar, a partir de la literatura científica, percepciones reales e ilusorias de pacientes adultos en coma inducido. Método: Revisión integrativa de 15 estudios primarios alojados en las bases de datos Medline, Web of Science, LILACS, CINAHL y SCOPUS. Resultados: Los recuerdos más reportados luego del coma inducido son sed, frío y dolor. Existen estudios en los que los pacientes afirmaron no distinguir si estaban despiertos o soñando, si era real o irreal. Se identificaron relatos de recuerdos satisfactorios relacionados al cuidado recibido y al uso diario de cabecera. Conclusión: Las evidencias mostraron un abanico de estudios cuyo objetivo era identificar el delirium, aunque con menor enfoque en la identificación real o ilusoria del paciente luego del coma inducido. Así, esta revisión integrativa consiguió identificar evidencias científicas acerca de los recuerdos relativos a la percepción del paciente sedado e internado en la Unidad de Terapia Intensiva.

RESUMO Objetivo: Identificar, a partir da literatura científica, percepções reais e ilusórias de pacientes adultos em coma induzido. Método: Revisão integrativa de 15 estudos primários localizados nas bases de dados Medline, Web of Science, LILACS, CINAHL e SCOPUS. Resultados: As principais memórias relatadas após o coma induzido são sede, frio e dor. Há estudos em que os pacientes afirmaram não distinguir se estavam acordados ou sonhando, se o que acontecia era real ou irreal. Identificaram-se relatos de memórias satisfatórias relacionadas ao cuidado recebido e ao uso de diários de cabeceira. Conclusão: As evidências mostraram um leque de estudos direcionados a identificar o delirium, porém com menor foco na identificação da percepção real ou ilusória do paciente após coma induzido. Desse modo, esta revisão integrativa proporcionou a identificação de evidências científicas sobre as memórias relativas à percepção do paciente sedado e em estadia na Unidade de Terapia Intensiva.

Comparison of Single and Combined Effects of Nature Sounds and Foot Sole Reflexology Massage on the Level of Consciousness in Traumatic Comatose Patients: A Randomized Controlled Clinical Trial.

Consciousness disturbances are the most common posttraumatic complications. The purpose of this study was to compare the single and combined effects of nature sounds and foot sole reflexology massage on level of consciousness in traumatic comatose patients. This randomized controlled clinical trial was conducted in 2 teaching hospitals in an urban area of Iran. Samples were 120 traumatic comatose patients who were randomly assigned into control, nature sounds, foot reflexology massage, and nature sounds plus foot sole reflexology massage groups. Patients in all groups received routine care. Interventions were performed twice a day for 2 weeks, each time for 30 minutes. The patients' level of consciousness was assessed using the Glasgow Coma Scale before, 1 week, and 2 weeks after the intervention. The groups had no significant differences in the mean scores of the consciousness level before, 1 week after, and the last day of the intervention. Also, there was a significant difference in the number of patients who regained full consciousness (P = .001) in the intervention groups compared with the control group. Significant differences in the number of days of consciousness were reported in at least one of the groups compared with other groups (P = .001). This difference was significant in the control group compared with the foot reflexology massage group (P = .032), as well as the nature sounds plus foot sole reflexology massage group (P = .001). Single or combined interventions can increase the level of consciousness in comatose patients and reduce the duration of coma.

Fulminant thymomatous AMPAR-antibody limbic encephalitis with hypertonic coma, bruxism, an isoelectric electroencephalogram and temporal cortical atrophy, with recovery.

Autoimmune encephalitides are a potentially devastating group of treatable disorders with a wide variety of clinical presentations. The most studied autoimmune encephalitis is caused by antibodies to the N-methyl-D-aspartate glutamate receptor. A rarer cause is due to antibodies against the evolutionarily related α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). The full assortment of electroencephalogram (EEG) and clinical descriptions of the latter are yet to be fully described. A 44-year-old woman with impaired consciousness and subsequent coma characterised by an isoelectric EEG was diagnosed with AMPAR-antibody limbic encephalitis. MRI revealed temporal T2 hyperintensities that improved with immunosuppression, although leaving marked cortical atrophy. Gradual clinical improvement saw the development of aggressive bruxism requiring botulinum toxin injection with eventual meaningful clinical recovery. This case expands the clinical spectrum of AMPAR limbic encephalitis to include aggressive bruxism, and highlights that despite poor clinical and EEG findings at the outset, recovery is still possible.

Comparison of the effects of nature sounds and reflexology on hemodynamic indices among traumatic comatose patients: A randomized controlled clinical trial.

Background Traumatic comatose patients may experience disturbances in hemodynamic indices due to the nature of their disorder. This study aimed to compare the effects of nature sounds and reflexology on hemodynamic indices in traumatic comatose patients. Methods This randomized clinical trial using a factorial design was conducted on 120 traumatic comatose patients in two teaching hospitals in two urban areas of Iran. The patients were selected using a sequential sampling method and assigned into randomized quadruple blocks as control, nature sounds, reflexology and nature sounds-reflexology (combined) groups. The interventions were performed twice daily in two consecutive days lasting 30 min each time. The hemodynamic indices were measured before, and immediately, 30 min, and 2 h after the intervention using calibrated monitors. Descriptive and inferential statistics, including one-way ANOVA, Scheffe ad hoc, repeated measure ANOVA, Bonferroni ad hoc Chi-square test and Fisher's exact tests were used for data analysis via the SPSS software V.16. Results Significant differences were reported in terms of the mean arterial pressure between the control and reflexology groups (p=0.002), and the combined group (p=0.008) immediately after the interventions. The combined group showed statistically differences in systolic blood pressure compared to the nature sounds (p=0.007) and control (p=0.015) groups 30 min after the interventions. The nature sounds group showed differences in the pulse rate from the reflexology (p=0.048) and control (p=0.015) groups 30 min after the interventions in the second day. Conclusions While the immediate effects of the interventions on induction of the feeling of relaxation and tranquility, and reduction of hemodynamic indices were reported, they diminished over time. Nature sounds and reflexology as low-cost and relaxing tranquilizing methods can be used for the reduction of tension and improvement of hemodynamic indices among traumatic comatose patients.

Death or Damnation: Surrogacy and Religious Beliefs.

MC is a 42-year-old female who was in a motor vehicle accident and suffered multiple contusions as well as a fracture of the left femur, pelvic ramus, and left orbit. Due to contusion of the brain, MC has been comatose for over a week and is on mechanical ventilation to protect her airway. There is no written declaration of surrogacy. During the admission, surgery to repair the left femoral fracture was performed and was complicated by severe blood loss. Currently, MC's hematocrit is 24% with a hemoglobin of 7.4. The trauma team asserts that a blood transfusion would be in MC's best interests. Since MC lacks capacity for decision making, she cannot consent to blood transfusion. Her parents are Jehovah's Witnesses and refuse to approve blood transfusion, stating that it is against their faith. MC's brother, however, states that MC is not a practicing Jehovah's Witness and wants the medical team to provide the blood transfusion. The parents insist that decision making is their right; MC's brother feels he should be making decisions. The trauma teams calls for an emergency consultation with the hospital ethics committee.

[Prolonged disorders of consciousness after an acute brain injury]. / Trastornos prolongados de conciencia postinjuria cerebral aguda.

Only a fraction of patients in coma secondary to a primary acute brain injury develop a vegetative state (VS). At least 20% of patients show late transitions to a minimally conscious states (MCS). They are particularly common in young adults with traumatic brain injury. The main problems faced by clinicians are the diagnostic accuracy of VS and MCS as well as the usefulness of sophisticated paraclinical investigations. Specific therapies are of limited effectiveness. This population is vulnerable to misdiagnosis and limited access to medical care and rehabilitation, thus generating ethical problems.

Serious adverse events and deaths linked to poor ventilator use: A report of four closed claims.

Through this series of four closed claims, we highlight examples of accidents stemming from poor ventilator use. We then review the main issues in this regard as reported in the literature and by learned societies. This case series has led us to emphasise the need for safety procedures involving systematic checks prior to use, declaration and analysis of the risk, as well as feedback and teaching regarding ventilation systems.

Diagnostic Accuracy of Procalcitonin for Early Aspiration Pneumonia in Critically Ill Patients with Coma: A Prospective Study.

BACKGROUND: Early diagnostic orientation for differentiating pneumonia from pneumonitis at the early stage after aspiration would be valuable to avoid unnecessary antibiotic therapy. We assessed the accuracy of procalcitonin (PCT) in diagnosing aspiration pneumonia (AP) in intensive care unit (ICU) patients requiring mechanical ventilation after out-of-hospital coma. METHODS: Prospective observational 2-year cohort study in a medical-surgical ICU. PCT, C-reactive protein (CRP) and white blood cell count (WBC) were measured at admission (H0) and 6 h (H), H12, H24, H48, H96, and H120 after inclusion. Lower respiratory tract microbiological investigations performed routinely in patients with aspiration syndrome were the reference standard for diagnosing AP. Performance of PCT, CRP, and WBC up to H48 in diagnosing AP was compared based on the areas under the ROC curves (AUC) and likelihood ratios (LR+ and LR-) computed for the best cutoff values. RESULTS: Of 103 patients with coma, 45 (44%) had AP. Repeated PCT assays demonstrated a significant increase in patients with AP versus without AP from H0 to H120. Among the three biomarkers, PCT showed the earliest change. ROC-AUC values were poor for all three biomarkers. Best ROC-AUC values for diagnosing AP were for CRP at H24 [0.73 (95%CI 0.61-0.84)] and PCT at H48 [0.73 (95%CI 0.61-0.84)]. LR+ was best for PCT at H24 (3.5) and LR- for CRP and WBC at H24 (0.4 and 0.4, respectively). CONCLUSIONS: Early and repeated assays of PCT, CRP, and WBC demonstrated significant increases in all three biomarkers in patients with versus without AP. All three biomarkers had poor diagnostic performance for ruling out AP. Whereas PCT had the fastest kinetics, PCT assays within 48 h after ICU admission do not help to diagnose AP in ICU patients with coma.

Postoperative myxedema coma in patients undergoing major surgery: Case series.

OBJECTIVE: Myxedema coma is a serious complication of hypothyroidism that can be precipitated by major surgery. It is extremely rare, with only a few reports in the literature. This study aims to present a relatively large case series of post-surgical myxedema coma and to analyze medical and surgical risk factors. METHODS: Analysis of the patients' surgical records and medical charts. RESULTS: Four patients developed postoperative myxedema coma and were evaluated for risk factors. Three had known hypothyroidism. Two had undergone large head and neck composite resections necessitating a free flap repair for malignant disease. One had undergone coronary artery bypass graft for ischemic heart disease, and another had undergone endoscopic cholecystectomy for complicated cholecystitis. All four patients required prolonged hospitalization, including treatment in the intensive care unit. One patient had undergone full cardiopulmonary resuscitation directly related to the myxedema coma state. CONCLUSION: We present a series of four patients who developed myxedema coma following major surgery. We recommend that patients with known hypothyroidism who are scheduled for major surgery should be tested for thyroid function status and assessed for postoperative risk of hypothyroidism. Those who develop complications following major surgery, should be immediately tested for thyroid function to rule out myxedema coma.