Electrical stimulation of the ventral tegmental area restores consciousness from sevoflurane-, dexmedetomidine-, and fentanyl-induced unconsciousness in rats.

BACKGROUND: Dopaminergic neurons in the ventral tegmental area (VTA) are crucially involved in regulating arousal, making them a potential target for reversing general anesthesia. Electrical deep brain stimulation (DBS) of the VTA restores consciousness in animals anesthetized with drugs that primarily enhance GABAA receptors. However, it is unknown if VTA DBS restores consciousness in animals anesthetized with drugs that target other receptors. OBJECTIVE: To evaluate the efficacy of VTA DBS in restoring consciousness after exposure to four anesthetics with distinct receptor targets. METHODS: Sixteen adult Sprague-Dawley rats (8 female, 8 male) with bipolar electrodes implanted in the VTA were exposed to dexmedetomidine, fentanyl, ketamine, or sevoflurane to produce loss of righting, a proxy for unconsciousness. After receiving the dopamine D1 receptor antagonist, SCH-23390, or saline (vehicle), DBS was initiated at 30 µA and increased by 10 µA until reaching a maximum of 100 µA. The current that evoked behavioral arousal and restored righting was recorded for each anesthetic and compared across drug (saline/SCH-23390) condition. Electroencephalogram, heart rate and pulse oximetry were recorded continuously. RESULTS: VTA DBS restored righting after sevoflurane, dexmedetomidine, and fentanyl-induced unconsciousness, but not ketamine-induced unconsciousness. D1 receptor antagonism diminished the efficacy of VTA stimulation following sevoflurane and fentanyl, but not dexmedetomidine. CONCLUSIONS: Electrical DBS of the VTA restores consciousness in animals anesthetized with mechanistically distinct drugs, excluding ketamine. The involvement of the D1 receptor in mediating this effect is anesthetic-specific.

Effects of STC on postoperative recovery of disturbance of consciousness in traumatic multiple intracranial hematoma patients.

OBJECTIVE: The study explored the therapeutic value of standard trauma craniectomy (STC) for the treatment of traumatic multiple intracranial hematoma. METHODS: Clinical data of traumatic multiple intracranial hematoma patients who underwent surgical treatment in 2014 and 2015 were collected. The STC group and a control group according to the surgical mode, 48 and 30 cases were randomly selected from each group, respectively. Statistical analysis was performed on the change in the Glasgow coma scale (GCS) score from before the operation to 1 day, 1 week and 1 month postoperatively through repeated analysis of variance and Wilcoxon rank-sum analysis. RESULTS: Significant differences in the GCS were observed at different time points for the two operative modes (P < .01), and an interaction was observed between time and treatment groups (P < .05). The rates of change of the GCS score for the two surgical modes were most obviously different at 3 days and 1 week postoperatively (P ≤ .001, P < .01). No statistically significant differences were observed in the rates of change of the GCS at 1 month postoperatively (P > .05). CONCLUSIONS: Compared to conventional craniotomy, STC has obvious effects on the recovery after disturbance of consciousness at 1 week postoperatively but does not result in a significant improvement in recovery at 1 month postoperatively.

Hyperpigmentation, severe alopecia, and six days of instability in a case of severe methotrexate hypersensitivity reaction.

INTRODUCTION: Ectopic pregnancy (EP) is an emergency condition in the gynecologic field. Methotrexate (MTX) is a drug of choice for the medical treatment of EP. Severe adverse events are rare among patients treated with MTX for this condition. REASON FOR REPORT: We describe a woman with severe multi-organ involvement experiencing about six days of instability after treatment with just a single-dose MTX for EP. This life-threatening condition is not common with a single dose of MTX. A 30-year-old healthy woman was treated medically with MTX for an EP. Three days later the patient was admitted to the emergency department of our hospital with generalized pustular rashes, alopecia, hyperpigmentation, nausea and vomiting, oral ulcers, and raised Creatinine level. Four days later due to pancytopenia, fever, and loss of consciousness, she was transferred to the intensive care unit and was intubated. OUTCOME: After 38 days of hospitalization, treatment was successful with leucovorin and supportive care and the patient's symptoms and clinical manifestations were regressed.

Trigeminal nerve electrical stimulation: An effective arousal treatment for loss of consciousness.

BACKGROUND: To determine if trigeminal nerve electrical stimulation (TNS) would be an effective arousal treatment for loss of consciousness (LOC), we applied neuroscientific methods to investigate the role of potential brain circuit and neuropeptide pathway in regulating level of consciousness. METHODS: Consciousness behavioral analysis, Electroencephalogram (EEG) recording, Chemogenetics, Microarray analysis, Milliplex MAP rat peptide assay, Chromatin immune-precipitation (ChIP), Dual-luciferase reporter experiment, Western blot, PCR and Fluorescence in situ hybridization (FISH). RESULTS: TNS can markedly activate the neuronal activities of the lateral hypothalamus (LH) and the spinal trigeminal nucleus (Sp5), as well as improve rat consciousness level and EEG activities. Then we proved that LH activation and upregulated neuropeptide hypocretin are beneficial for promotion of consciousness recovery. We then applied gene microarray experiment and found hypocretin might be mediated by a well-known transcription factor Early growth response gene 1 (EGR1), and the results were confirmed by ChIP and Dual-luciferase reporter experiment. CONCLUSION: This study illustrates that TNS is an effective arousal strategy Treatment for LOC state via the activation of Sp5 and LH neurons and upregulation of hypocretin expression.

Loss of Consciousness and Altered Mental State as Predictors of Functional Recovery Within 6 Months Following Mild Traumatic Brain Injury.

OBJECTIVE: The authors tested the hypothesis that a combination of loss of consciousness (LOC) and altered mental state (AMS) predicts the highest risk of incomplete functional recovery within 6 months after mild traumatic brain injury (mTBI), compared with either condition alone, and that LOC alone is more strongly associated with incomplete recovery, compared with AMS alone. METHODS: Data were analyzed from 407 patients with mTBI from Head injury Serum Markers for Assessing Response to Trauma (HeadSMART), a prospective cohort study of TBI patients presenting to two urban emergency departments. Four patient subgroups were constructed based on information documented at the time of injury: neither LOC nor AMS, LOC only, AMS only, and both. Logistic regression models assessed LOC and AMS as predictors of functional recovery at 1, 3, and 6 months. RESULTS: A gradient of risk of incomplete functional recovery at 1, 3, and 6 months postinjury was noted, moving from neither LOC nor AMS, to LOC or AMS alone, to both. LOC was associated with incomplete functional recovery at 1 and 3 months (odds ratio=2.17, SE=0.46, p<0.001; and odds ratio=1.80, SE=0.40, p=0.008, respectively). AMS was associated with incomplete functional recovery at 1 month only (odds ratio=1.77, SE=0.37 p=0.007). No association was found between AMS and functional recovery in patients with no LOC. Neither LOC nor AMS was predictive of functional recovery at later times. CONCLUSIONS: These findings highlight the need to include symptom-focused clinical variables that pertain to the injury itself when assessing who might be at highest risk of incomplete functional recovery post-mTBI.

Tonic-clonic seizure during the ultrasound-guided stellate ganglion block because of an injection into an unrecognized variant vertebral artery: A case report.

RATIONALE: Recent years have witnessed a marked improvement in the safety and accuracy of nerve blocks with the help of ultrasound and other visualization technologies. This study reports a challenging case of a severe complication during the ultrasound-guided stellate ganglion block. PATIENT CONCERNS: A 28-year-old male patient with refractory migraine complained episodic pulsatile pain with photophobia, haphalgesia of the scalp for 3 years. INTERVENTIONS: Ultrasound-guided stellate ganglion block with 4 ml of 1% lidocaine was administrated. OUTCOMES: A sudden loss of consciousness and tonic-clonic seizure was occurred after negative aspiration and test dose. Further sonographic examination revealed a variation in the left vertebral artery, which remained unrecognized during the needle insertion because of its sliding ability under the differential pressure applied by the probe. LESSONS: Inadvertent intra-arterial injection of a local anesthetic agent could be minimized under the ultrasound guidance with various protective strategies, including the determination of any prior variation, optimizing the block route, maintaining a constant probe pressure, and using saline for the test dosage. This case resulted in the implementation of new protocols of the ultrasound-guided stellate ganglion block in our department.

[A retrospective analysis of the management of unconscious patients from the emergency room (ER) to intensive care (ICU) at Södersjukhuset]. / Fler medvetslösa patienter bör intuberas för säkrad luftväg - Många medvetslösa vårdas också för kort tid på IVA ­ möjliga donatorer missas, visar retrospektiv analys.

Intubation and admission to ICU are vital stages in the management of unconscious patients. Treatment records for all patients who died within 5 days of admission to Södersjukhuset during 2015 were obtained. Patients with GCS <9 in the ER were selected. It was noted if the patients had been intubated, had done a CT brain scan and if they had been admitted to ICU. They were divided into one of three diagnosis groups: cardiac arrest, intracerebral hemorrhage/stroke or other. 48 of 51 cardiac arrest patients were intubated and transferred to ICU. Only 17 of 46 ICH/stroke patients were intubated, and 22 ICH/stroke patients did a CT brain scan with an unprotected airway. Possible organ donors were more difficult to detect in the cardiac arrest group (6 of 14 possible) compared with the ICH/stroke group (12 of 14 possible). Our analysis shows that improvements need to be made in the airway management of unconscious patients who have suffered an ICH or stroke, and that identification of possible organ donors amongst victims of cardiac arrest also needs to be improved.

[Acute unconsciousness]. / Akute Bewusstseinsstörung.

Emergency treatment of unconscious patients is a complex task and should follow a standardised algorithm. Stabilisation of vital parameters, diagnostic procedures, and therapeutic interventions should be carried out in part simultaneously and require interdisciplinary teamwork. Diagnosis has to be made under high time pressure in order to recognize life threatening causes and initiate specific treatments. Often, the earlier the treatment starts, the better the outcome is.

A systematic approach to the unconscious patient.

Unconscious patients are commonly seen by physicians. They are challenging to manage and in a time sensitive condition, a systematic, team approach is required. Early physiological stability and diagnosis are necessary to optimise outcome. This article focuses on unconscious patients where the initial cause appears to be non-traumatic and provides a practical guide for their immediate care.

Lifetime History of Traumatic Brain Injury and Current Disability Among Ohio Adults.

OBJECTIVE: To examine the associations between lifetime history of traumatic brain injury (TBI) with loss of consciousness (LOC) and several types of current disability among adult, noninstitutionalized residents of Ohio. PARTICIPANTS: 2014 Ohio Behavioral Risk Factors Surveillance System participants (n = 6998). DESIGN: Statewide population-based survey. MAIN MEASURES: Lifetime history of TBI with LOC (number and severity of injury, age of first injury), and number and type of disability (vision, cognition, mobility, self-care, and/or independent living). RESULTS: Of the 6998 participants, 1325 reported lifetime history of TBI with LOC, and 1959 reported currently having one or more disabilities. When weighted, these represented 21.7% and 23.7% of Ohio's noninstitutionalized adult population, respectively. Adults with a history of TBI with LOC showed greater odds of any disability compared with adults with no history (odds ratio = 2.49; 95% confidence interval = 1.97-3.15). The likelihood of having any and each type of disability increased as the number of TBIs or the severity of worst TBI increased, regardless of sustaining first TBI before or after the age of 15 years. CONCLUSIONS: Lifetime history of TBI with LOC is significantly associated with disability among Ohio adults. Further research on the natural course of the relation and preventive strategies is warranted.

Using best interests meetings for people in a prolonged disorder of consciousness to improve clinical and ethical management.

Current management of people with prolonged disorders of consciousness is failing patients, families and society. The causes include a general lack of concern, knowledge and expertise; a legal and professional framework which impedes timely and appropriate decision-making and/or enactment of the decision; and the exclusive focus on the patient, with no legitimate means to consider the broader consequences of healthcare decisions. This article argues that a clinical pathway based on the principles of (a) the English Mental Capacity Act 2005 and (b) using time-limited treatment trials could greatly improve patient management and reduce stress on families. There needs to be early and continuing use of formal best interests meetings, starting between 7 and 21 days after onset of unconsciousness (from any cause, including progressive disorders). The treatment options need to evolve as the clinical state and prognosis becomes more certain. A formal discussion of treatment withdrawal should occur when the upper bound of predicted recovery falls below a level the patient would have considered acceptable, and it should always be discussed when the condition is considered permanent. Any decision to stop treatment should be contingent on a formal second opinion from an independent expert who should review the clinical situation and expected prognosis, but not the best interests decision. The article also asks how, if at all, the adverse effects on the family and the resource implications of long-term care of people left in a prolonged state of unconsciousness should be incorporated in the process.

[Unconsciousness and clouded awareness]. / Bewusstseinsstörung oder -trübung.

Stupor and coma are clinical states in which patients have impaired responsiveness or are unresponsive to external stimulation and are either difficult to arouse or are unarousable. The term stupor refer to states between alertness and coma. An alteration in arousal represents an acute life-threatening emergency, requiring prompt intervention for preservation of life and brain function.

Unusual presentation of local anesthetic toxicity.

The local anesthetic systemic toxicity can be due to increased blood lignocaine levels or due to increased sensitivity to lignocaine. Several cases of lignocaine-induced central nervous system toxicity have been noted, but none have reported only loss of consciousness without any seizure-like activity. Intravenous lipid emulsion administration for the treatment of local anesthetic systemic toxicity is an emerging topic of discussion, and there are case reports where they had successfully been used. However, majority of them were used in the treatment of cardiovascular manifestations of local anesthetic toxicity. We report a case of a 19-year-old man who had unconsciousness on 2 separate occasions after local lignocaine infiltration to undergo surgery for dental malocclusion and the use of lipid emulsion in its management.

Analytically Confirmed Intoxications Involving MDMB-CHMICA from the STRIDA Project.

INTRODUCTION: About a decade ago, synthetic cannabinoids (SC) started to appear as recreational drugs on the new psychoactive substance (NPS) market. This report from the STRIDA project describes analytically confirmed intoxications involving MDMB-CHMICA (methyl-2-(1-(cyclohexylmethyl)-1H-indol-3-ylcarbonylamino)-3,3-dimethylbutanoate), a SC that was first detected in 2014. STUDY DESIGN: This is an observational case series of patients from Sweden with suspected NPS exposure presenting in emergency departments and intensive care units. The results of retrospective serum and urine toxicological analysis were compared with clinical signs reported during consultation with the Poisons Information Centre and retrieved from medical records. METHODS: Clinical and bioanalytical data in nine acute intoxications associated with MDMB-CHMICA during 2014-2015 are presented. The patients were aged 23-62 (median 34) years, and eight were men. MDMB-CHMICA (parent compound) was analytically confirmed in serum samples, using a liquid chromatography-high-resolution mass spectrometry multi-component method. RESULTS: Of the nine MDMB-CHMICA-positive patients, eight had a Poisoning Severity Score (PSS) of 2 or 3, and five were monitored in the intensive care unit and all patients survived. Development of seizures and deep unconsciousness were common features. All cases except one also tested positive for other NPS and/or classical psychoactive compounds, hampering the possibility to establish a causal relationship between drug and toxic symptoms. MDMB-CHMICA was also identified in seven drug materials donated by the patients. CONCLUSIONS: The association with severe adverse reactions in nine acute analytically confirmed intoxication cases involving MDMB-CHMICA is consistent with other reports of serious toxicity linked to this substance, suggesting that MDMB-CHMICA might be a particularly harmful SC.

Effect of aphasia on acute stroke outcomes.

OBJECTIVE: To determine the independent effects of aphasia on outcomes during acute stroke admission, controlling for total NIH Stroke Scale (NIHSS) scores and loss of consciousness. METHODS: Data from the Tulane Stroke Registry were used from July 2008 to December 2014 for patient demographics, NIHSS scores, length of stay (LOS), complications (sepsis, deep vein thrombosis), and discharge modified Rankin Scale (mRS) score. Aphasia was defined as a score >1 on question 9 on the NIHSS on admission and hemiparesis as >1 on questions 5 or 6. RESULTS: Among 1,847 patients, 866 (46%) had aphasia on admission. Adjusting for NIHSS score and inpatient complications, those with aphasia had a 1.22 day longer LOS than those without aphasia, whereas those with hemiparesis (n = 1,225) did not have any increased LOS compared to those without hemiparesis. Those with aphasia had greater odds of having a complication (odds ratio [OR] 1.44, confidence interval [CI] 1.07-1.93, p = 0.0174) than those without aphasia, which was equivalent to those having hemiparesis (OR 1.47, CI 1.09-1.99, p = 0.0137). Controlling for NIHSS scores, aphasia patients had higher odds of discharge mRS 3-6 (OR 1.42 vs 1.15). CONCLUSION: Aphasia is independently associated with increased LOS and complications during the acute stroke admission, adding $2.16 billion annually to US acute stroke care. The presence of aphasia was more likely to produce a poor functional outcome than hemiparesis. These data suggest that further research is necessary to determine whether establishing adaptive communication skills can mitigate its consequences in the acute stroke setting.

A Descriptive Analysis of Therapeutic Hypothermia Application Across Adult Age Groups.

Therapeutic hypothermia (TH) has been recommended for comatose adults recovering from out-of-hospital cardiac arrest (OHCA) for a decade. However, TH has never been evaluated in a randomized control trial in patients aged 75 or older. How the administration of TH varies across age groups experiencing an OHCA is unknown. The objective was to describe the use of TH across predefined age groups with an emphasis on geriatric OHCA survivors using data compiled through Cardiac Arrest Registry to Enhance Survival (CARES). We hypothesized that TH provision would decline in patients aged 75 or older. This was a secondary analysis of prospectively collected and verified registry data. The study was Institutional Review Board exempt. Through December 2013, CARES had 130,852 completed records for consideration. All nontraumatic adult index arrests of presumed cardiac etiology with attempted resuscitation were study eligible. Sustained return of spontaneous circulation with survival to hospital admission was a prerequisite for inclusion. Exclusion criteria were as follows: records before November 2010 when TH became a mandatory reporting field; pre-existing Do Not Resuscitate directive; missing TH status or outcome classification; and OHCA location and timing variables potentially affecting treatment decisions or eligibility. All records in our final sample were categorized (TH or no TH) for descriptive analysis. Our final sample size was 11,533. The percentage of patients <75 who received TH was 58.5% (95% CI: 57.5-59.6) and 46.4% (95% CI: 44.5-48.3) for those 75 or older. There was no difference in the rate of TH across the age groups from <25 to 65-74 (p = 0.205). Treatment rates significantly decreased from age 75-84 to 95+ (p < 0.001). There is a significant decline in the provision of TH at age 75 years within CARES. Further research is needed to determine if age is an independent predictor of TH underutilization in the elderly.