Tocilizumab is associated with reduced delirium and coma in critically ill patients with COVID-19.

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.

Clinical Results of Accelerated Iontophoresis-Assisted Epithelium-on Corneal Cross-linking for Progressive Keratoconus in Children.

PURPOSE: To evaluate the clinical characteristics of pediatric patients with progression of keratoconus after accelerated iontophoresis-assisted epithelium-on corneal cross-linking (I-ON CXL) and to assess the efficacy and safety of re-treatment using accelerated epithelium-off CXL (epi-OFF CXL). METHODS: Sixteen eyes of 16 patients (mean age: 14.6 ± 2.5 years) with keratoconus underwent I-ON CXL. The main outcome measures were uncorrected distance visual acuity, corrected distance visual acuity, maximum keratometry index (Kmax), minimum corneal thickness, elevation front and elevation back measured at the thinnest point, total higher order aberrations root main square (HOA RMS), coma RMS, and spherical aberration. An increment of Kmax greater than 1.00 diopter (D) and a decrease of greater than 20 µm in pachymetry were considered to determine the progression of keratoconus. Patients with progression of keratoconus after I-ON CXL were re-treated using an epi-OFF CXL protocol. RESULTS: Two years after I-ON CXL, 12 patients showed progression of keratoconus, whereas 4 patients were stable. There was significant worsening of Kmax (P = .04) and steepest keratometric reading (P = .01). Furthermore, a significant correlation was documented between progression of keratoconus and age (P = .02). These patients were re-treated using an epi-OFF protocol and after 2 years all patients were stable, and a statistically significant reduction of the mean Kmax (P = .007), HOA RMS (P = .05), and coma RMS (P = 05) was observed. CONCLUSIONS: I-ON CXL was ineffective in the treatment of pediatric keratoconus in younger children, whereas it had an efficacy of 2 years in older children. Re-treatment using epi-OFF CXL proved effective to halt progression of keratoconus after I-ON CXL failure. [J Pediatr Ophthalmol Strabismus. 2024;61(1):44-50.].

Central versus paracentral cone location and outcomes of accelerated cross-linking in keratoconus patients.

PURPOSE: To compare outcomes 1 year after accelerated cross-linking (CXL) between keratoconus eyes with central cones to those with paracentral cones. METHODS: In this post hoc analysis of data from a prospective multicentre study, consecutive progressive keratoconus eyes treated with accelerated CXL were included. Preoperative and 1 year post CXL manifest refraction, corneal cylinder, maximal keratometry (Kmax), central corneal thickness and coma were assessed. Central and paracentral cones were defined as cones within the central 3 mm and those between 3 and 5 mm, respectively. Eyes with apical scarring and peripheral cones (>5 mm) were excluded. The primary outcome measures were changes in best spectacle-corrected visual acuity (BSCVA) and Kmax. RESULTS: Overall, 314 eyes (n = 314) with a mean age of 27.5 ± 7.7 years were included. At baseline, the central cone group was younger (p < 0.001), had lower corneal astigmatism (p = 0.03) and coma (p = 0.02). At 1 year post CXL, after adjusting for baseline characteristics (age, BSCVA, corneal astigmatism, Kmax and coma), the central cone group showed a greater reduction in myopia (mean difference 1.27 ± 0.60D, p = 0.04) and more improvement in BSCVA (mean difference 0.08 ± 0.02 logMAR, p < 0.001) compared to the paracentral group. There was no significant difference in progression rates between the central and paracentral groups (ΔKmax > 2D, 6.7% vs. 6.5%, respectively, p = 0.83). CONCLUSIONS: This large-scale study of keratoconus eyes 1 year after accelerated CXL indicates that compared to those with paracentral cones, central cones have on average almost one additional line improvement in BCSVA and 1.27 D more reduction in myopia.

Effects of Xingnaojing Injection on Adenosinergic Transmission and Orexin Signaling in Lateral Hypothalamus of Ethanol-Induced Coma Rats.

Acute alcohol exposure induces unconscious condition such as coma whose main physical manifestation is the loss of righting reflex (LORR). Xingnaojing Injection (XNJI), which came from Chinese classic formula An Gong Niu Huang Pill, is widely used for consciousness disorders in China, such as coma. Although XNJI efficiently shortened the duration of LORR induced by acute ethanol, it remains unknown how XNJI acts on ethanol-induced coma (EIC). We performed experiments to examine the effects of XNJI on orexin and adenosine (AD) signaling in the lateral hypothalamic area (LHA) in EIC rats. Results showed that XNJI reduced the duration of LORR, which implied that XNJI promotes recovery form coma. Microdialysis data indicated that acute ethanol significantly increased AD release in the LHA but had no effect on orexin A levels. The qPCR results displayed a significant reduction in the Orexin-1 receptors (OX1R) expression with a concomitant increase in the A1 receptor (A1R) and equilibrative nucleoside transporter type 1 (ENT1) expression in EIC rats. In contrast, XNJI reduced the extracellular AD levels but orexin A levels remained unaffected. XNJI also counteracted the downregulation of the OX1R expression and upregulation of A1R and ENT1 expression caused by EIC. As for ADK expression, XNJI but not ethanol, displayed an upregulation in the LHA in EIC rats. Based on these results, we suggest that XNJI promotes arousal by inhibiting adenosine neurotransmission via reducing AD level and the expression of A1R and ENT1.

Myxedema coma precipitated by diabetic ketoacidosis after total thyroidectomy: a case report.

BACKGROUND: Myxedema coma is profound decompensated hypothyroidism usually precipitated by stressors, and its occurrence in association with total thyroidectomy or metabolic disorders, such as diabetic ketoacidosis, is unusual. CASE PRESENTATION: A 43-year-old Asian man with history of total thyroidectomy who was scheduled for a second radioactive iodine therapy presented to our hospital with decreased mental status and hyperglycemia. He had a history of thyroid cancer but did not have diabetes mellitus. He was in a hypothermic state and had a Glasgow Coma Scale score of 10 out of 15 at presentation; arterial blood gas analysis revealed a state of metabolic acidosis and laboratory findings suggested hyperglycemia with glycosuria, ketoacidosis, and severe hypothyroidism. A thyroid function test showed thyroid-stimulating hormone of 34.126 uIU/mL, free thyroxine of 1.02 ng/dL, and triiodothyronine of 1.04 ng/mL. The glycated hemoglobin of this patient was checked due to hyperglycemia and the value of glycated hemoglobin was 16.5% which met the criteria for a diagnosis of diabetes. After treatment for myxedema with liothyronine 5 mcg two times per day and levothyroxine 175 mcg once daily via a nasogastric tube and diabetic ketoacidosis with intravenously administered fluid and insulin, his clinical condition rapidly improved including mental status, hyperglycemia, and acidosis. During the hospitalization, a workup for diabetes mellitus was performed and the results suggested that a diagnosis of type 2 diabetes mellitus would be appropriate. CONCLUSIONS: This case demonstrated that diabetic ketoacidosis not only could be a potential contributor to myxedema coma but also mask typical clinical features, making diagnosis more difficult. Considering the possibility of an increasing number of potential patients with hypothyroidism developed after thyroidectomy, constant vigilance is required for a better clinical outcome, including early recognition and management in critical care in advance for unusual diabetic ketoacidosis which could precipitate decompensated hypothyroidism.

Neurostimulant use is associated with improved survival in comatose patients after cardiac arrest regardless of electroencephalographic substrate.

AIM: Identify EEG patterns that predict or preclude favorable response in comatose post-arrest patients receiving neurostimulants. METHODS: We examined a retrospective cohort of consecutive electroencephalography (EEG)-monitored comatose post-arrest patients. We classified the last day of EEG recording before neurostimulant administration based on continuity (continuous/discontinuous), reactivity (yes/no) and malignant patterns (periodic discharges, suppression burst, myoclonic status epilepticus or seizures; yes/no). In subjects who did not receive neurostimulants, we examined the last 24h of available recording. For our primary analysis, we used logistic regression to identify EEG predictors of favorable response to treatment (awakening). RESULTS: In 585 subjects, mean (SD) age was 57 (17) years and 227 (39%) were female. Forty-seven patients (8%) received a neurostimulant. Neurostimulant administration independently predicted improved survival to hospital discharge in the overall cohort (adjusted odds ratio (aOR) 4.00, 95% CI 1.68-9.52) although functionally favorable survival did not differ. No EEG characteristic predicted favorable response to neurostimulants. In each subgroup of unfavorable EEG characteristics, neurostimulants were associated with increased survival to hospital discharge (discontinuous background: 44% vs 7%, P=0.004; non-reactive background: 56% vs 6%, P<0.001; malignant patterns: 63% vs 5%, P<0.001). CONCLUSION: EEG patterns described as ominous after cardiac arrest did not preclude survival or awakening after neurostimulant administration. These data are limited by their observational nature and potential for selection bias, but suggest that EEG patterns alone should not affect consideration of neurostimulant use.

Homeopathic treatment for prolonged postoperative coma: a case report.

Coma is the state of unrousable unconsciousness. There are variations in the degree of coma and the findings and signs found on the patient's clinical examination depend on the underlying cause of the disorder. The Glasgow Coma scale evaluates the best motor, verbal and eye answers of the patient. A patient is considered to be in a coma if his Glasgow Coma Scale is below 8 points. The progress that we have made throughout the years has also led to complications that can culminate in a major catastrophe like death, permanent brain damage, coma. A study performed reached the conclusion that prior comorbidity, older age, intraoperative hypotension, and cardiovascular surgery may predispose patients to postoperative coma. The article presents a case of postoperative coma treated successfully with homeopathy. Although a rare complication, postoperative coma is a severe, death-leading condition, causing immense suffering on both the patient and the patient's family. A multidisciplinary and thorough approach is necessary for these patients, but even after a well-conducted therapy, this condition leads to the death of the patient.

Successful treatment of a patient with ethylmalonic encephalopathy by intravenous N-acetylcysteine.

Ethylmalonic encephalopathy (EE) is an autosomal recessive devastating metabolic disorder affecting the brain, gastrointestinal tract, peripheral vessels and rarely the other vascular organs. We report a 10-month-old girl who presented as a meningococcemia clinic but later diagnosed ethylmalonic encephalopathy. Molecular analyses revealed a homozygous c.554 T > G; p. L185R mutation in ETHE1 gene. She was only partially benefited from riboflavine, coenzyme Q10, metronidazole, N-acetylcysteine and symptomatic treatment and discharged from hospital with the sequela of oxygene dependance and developmental delay. We observed N-acetylcysteine 100 mg/kg/day intravenous infusion theraphy may be the most important drug especially in comatous EE patients.

Refractory status epilepticus: new insights in presentation, treatment, and outcome.

Refractory status epilepticus (RSE), defined as status epilepticus that fails to respond to the acute administration of two antiepileptic medications, occurs in approximately a third of patients with status epilepticus, and is associated with increased hospital length of stay, mortality, and functional disability. Common presentations include: (1) generalized convulsive status epilepticus or complex partial status epilepticus that continue despite initial therapies; (2) stupor or coma following a generalized convulsive or complex partial seizure; or (3) stupor or coma following brain surgery or acute brain injury. When status epilepticus continues or recurs 24 hours or more after the initiation of anesthetic therapy, or recurs on the reduction or withdrawal of anesthesia, it is termed super RSE. Published evidence on optimal management of RSE consists largely of case reports or small series. The mainstay of treatment is the administration of anesthetic agents titrated to electrographic seizure control. Adjunctive therapies include hypothermia and immunosuppression and less commonly, surgery, electrical stimulation therapies, and induction of ketosis. Patients with cardiopulmonary complications and prolonged duration of drug-induced coma tend to have worse post-treatment functional outcomes. However, significant improvement over time can occur in survivors, and thus treatment is justified even in patients who require prolonged anesthetic coma. The strongest predictors of outcome are duration of anesthetic coma, etiology, and development of cardiopulmonary complications.

[Pituitary coma]. / Hypophysäres Koma.

Severe or inadequately substituted insufficiency of corticotropic and/or thyrotropic pituitary axes may induce a life-threatening coma. Without any information on patient history the primary diagnosis is difficult but clinical signs of hypogonadism may be helpful. Laboratory diagnostics reveal low serum concentrations of the hormones of the pituitary and the target organs. Low sodium concentrations are induced by stimulated ADH secretion and coincidental hypoglycemia may aggravate the situation. Initial treatment is based on the early substitution of hydrocortisone and is followed by thyroxine substitution according to the laboratory results at an intensive care unit where other coincidental problems also need to be monitored and treated. Differential diagnosis of pituitary pathology and definition of long-term treatment follow after stabilization of the patient's condition.

Early survival of comatose patients after severe traumatic brain injury with the dual cannabinoid CB1/CB2 receptor agonist KN38-7271: a randomized, double-blind, placebo-controlled phase II trial.

UNLABELLED: BACKGROUND AND STUDY OBJECT: Despite many drug trials, no substance has yet been identified that improves the outcome of severe head injury. The dual cannabinoid CB1/CB2 receptor agonist KN38-7271 mediates potent neuroprotection in animal models. We describe here the first randomized, double-blind, prospective, placebo-controlled clinical phase IIa proof-of-concept trial to investigate the safety, pharmacokinetics, and potential efficacy of a cannabinoid receptor agonist in humans. PATIENTS AND METHODS: Out of the 439, 97 comatose patients at 14 European neurosurgical centers met the inclusion criteria. KN38-7271 was administered within 4.5 hours of the injury, and the patients received 1000, 500 µg, or placebo. The primary analysis was pharmacokinetic; efficacy was measured by survival and by neurological improvement or deterioration 7 and 14 days and 1, 3, and 6 months after the injury. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were analyzed from start of treatment to end of day 7. RESULTS: Survival rates within 1 month of the injury were significantly better in the treatment groups than in the placebo group (high-dose, Kaplan-Meier difference on day 30 + 0.12 with p = 0.043; low-dose, difference +0.15 with p = 0.011) but this effect was not seen after 6 months. Critical ICP and CPP were less extreme and less frequent in the treatment group. There were no severe and no serious adverse effects that could be attributed to KN38-7271. CONCLUSIONS: KN38-7271 appeared beneficial in the acute early phase of the comatose patient after a head injury. Its use was safe and well tolerated by patients. These results may provide the basis for further phase II/III trials in larger study populations.

[Comatose patient with neuroleptic malignant syndrome brought by ambulance].

A 27-year-old woman with schizophrenia showed signs of neuroleptic malignant syndrome with disturbed consciousness, high fever, muscle rigidity, and autonomic dysfunction (including tachycardia and enhancement of saliva secretion). Since the age of 15, she had been treated at a local psychiatric clinic with a diagnosis of schizophrenia. On the day she was brought to the emergency room, she was asleep in the morning, but tachycardia was observed in the evening in the absence of consciousness. The patient was brought to our hospital by ambulance. It was revealed that she had taken a massive dose of chlorpromazine hydrochloride in the morning on the same day. On arrival, the Japan coma scale, pulse, respiratory rate, body temperature, and Sp(O2) were 300, 114 beats x min(-1), 26 breaths x min(-1), 39.0 degrees, and 91% (room air), respectively. The CPK level was 1,776 IU x l(-1). Sp(O2), bilateral pneumonia, and right atelectasis improved 2 hours after admission. Endotracheal intubation was performed for artificial respiration. Salivation, marked sweating, and rigidity of the limbs were noted. Under a diagnosis of neuroleptic malignant syndrome, dantrolene was administered. For pneumonia, ceftriaxone and pazufloxacin were administered. The consciousness became clear 2 days after admission. The patient was discharged 10 days after admission.

[Comatose state caused by seizure-free status epilepticus in postoperative period].

We present a rare clinical observation of progressive development of neurological symptoms up to comatose state in a child with extra-intraventricular craniopharyngioma in delayed postoperative period due to seizure-free status epilepticus which was diagnosed only by EEG-monitoring. Concerning this case report, we discuss genesis of seizure-free status epilepticus and its possible role in development of severe condition in patients with different kinds of neurosurgical pathology in postoperative period.

Myxedema coma after esophagectomy.

For most patients with esophageal cancer, esophagectomy is an effective therapy. Perioperative management is critical for clinical outcomes after the operation. Great efforts should be made to avoid postoperative complications. We report myxedema coma, an emergency condition caused by severe hypothyroidism, after a patient underwent esophagectomy for esophageal cancer. The patient was successfully treated with intravenous levothyroxine. We strongly recommend that physicians test the thyroid hormone levels in patients with risk factors. If myxedema coma occurs, immediate use of intravenous levothyroxine is effective for this lethal complication.

Cerebral venous thrombosis: analysis of a multicenter cohort from the United States.

OBJECTIVE: The data regarding diagnosis, prognosis, management, and outcome of patients with cerebral venous thrombosis are limited from the United States. METHODS: Patients with diagnosis of cerebral venous thrombosis were identified by International Classification of Diseases, Ninth Revision coding system at 10 centers in the United States during a 10-year period by retrospective chart review (1991-1997) or prospective enrollment (1997-2001). In all, 232 patients were screened for study inclusion and 182 of these patients were included in the study. RESULTS: The age range was 13 to 82 years (mean 38 years). Hypercoagulable state was the most common predisposing factor followed by pregnancy, malignancy, and homocystinemia. Neurologic examination revealed normal findings in 69 patients (38%); 37 (20%) were comatose, 59 (32%) had papilledema, and 71 (39%) had hemiparesis. In all, 61 patients (33%) had evidence of hemorrhage by computed tomography/magnetic resonance imaging. A total of 27 patients (15%) were treated with thrombolysis and 124 (68%) with anticoagulation. Overall mortality was 13% (n = 24). One-year follow up was available for 96 patients (53%). Of these, 26 (27%) were healthy, 43 (45%) were ambulatory with assistance, and 27 (28%) were still bedridden. On multivariate analysis, the best predictors of a poor outcome were coma at presentation (odds ratio 15.2 [95% confidence interval; 1.5-66]) and intracerebral hemorrhage (odds ratio 8.7 [95% confidence interval; 1.3-34.5]). CONCLUSION: Clinical and radiologic presentation of cerebral venous thrombosis in the United States is not much different from other parts of world but spectrum and frequency of predisposing factors are different. Number of patients treated with thrombolysis is higher as compared with other reported series of such patients. Coma at presentation and intracerebral hemorrhage were the strongest predictors of poor outcome, which is comparable with other series.

Asynchronous burst-suppression in a child with callosal Ki-1 anaplastic large cell lymphoma.

A 13-year-old girl with Ki-1 anaplastic large cell lymphoma (Ki-1ALCL) bulky deposits in the brain developed raised intracranial pressure and coma associated with asynchronous burst-suppression following standard dose cranial irradiation. Supportive care, steroids, and chemotherapy resulted in clinical improvement. Burst-suppression coma may be reversible when secondary to tumor, decrease in steroids, or radiation effects; the asynchrony localizes the lesion to cortical interconnections such as the corpus callosum.