Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Longitudinal associations of plasma amino acid levels with recovery from malarial coma.

BACKGROUND: Disordered amino acid metabolism is observed in cerebral malaria (CM). This study sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. Twenty-one amino acids and coma scores were quantified longitudinally and the data were analysed for associations. METHODS: In a prospective observational study, 42 children with CM were enrolled. Amino acid levels were measured at entry and at frequent intervals thereafter and consciousness was assessed by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. Logistic regression was employed using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS. RESULTS: At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analysed at each sampling time. CONCLUSION: Longitudinal data is provided for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation and may contribute to CM pathogenesis.

Association of diabetic ketoacidosis and HbA1c at onset with year-three HbA1c in children and adolescents with type 1 diabetes: Data from the International SWEET Registry.

OBJECTIVE: To establish whether diabetic ketoacidosis (DKA) or HbA1c at onset is associated with year-three HbA1c in children with type 1 diabetes (T1D). METHODS: Children with T1D from the SWEET registry, diagnosed <18 years, with documented clinical presentation, HbA1c at onset and follow-up were included. Participants were categorized according to T1D onset: (a) DKA (DKA with coma, DKA without coma, no DKA); (b) HbA1c at onset (low [<10%], medium [10 to <12%], high [≥12%]). To adjust for demographics, linear regression was applied with interaction terms for DKA and HbA1c at onset groups (adjusted means with 95% CI). Association between year-three HbA1c and both HbA1c and presentation at onset was analyzed (Vuong test). RESULTS: Among 1420 children (54% males; median age at onset 9.1 years [Q1;Q3: 5.8;12.2]), 6% of children experienced DKA with coma, 37% DKA without coma, and 57% no DKA. Year-three HbA1c was lower in the low compared to high HbA1c at onset group, both in the DKA without coma (7.1% [6.8;7.4] vs 7.6% [7.5;7.8], P = .03) and in the no DKA group (7.4% [7.2;7.5] vs 7.8% [7.6;7.9], P = .01), without differences between low and medium HbA1c at onset groups. Year-three HbA1c did not differ among HbA1c at onset groups in the DKA with coma group. HbA1c at onset as an explanatory variable was more closely associated with year-three HbA1c compared to presentation at onset groups (P = .02). CONCLUSIONS: Year-three HbA1c is more closely related to HbA1c than to DKA at onset; earlier hyperglycemia detection might be crucial to improving year-three HbA1c.

Predictive Value and Correlation of Neuron-Specific Enolase for Prognosis in Patients with Coma: A Systematic Review and Meta-Analysis.

OBJECTIVE: Coma is the most serious disturbance of consciousness, which affects the life quality of patients and increases the burden of their family. Studies to assess the prognostic value of neuron-specific enolase (NSE) in patients with coma have not led to precise, generally accepted prognostic rules. The study aims to assess the correlation between NSE and prognosis of coma and the predictive value of NSE for clinical prognosis. METHODS: A search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data from the establishment time of databases to December 2019. This analysis included patients with coma, regardless of how long the coma was. In total, 26 articles were retrieved and included in the review. RESULTS: The meta-analysis revealed the NSE concentration of patients with coma is significantly higher than that of the control group (standard mean difference = 0.88, 95% confidence interval [CI]: 0.63-1.12, p < 0.05). The pooled sensitivity and specificity of NSE in coma diagnosis was 0.5 (95% CI: 0.39-0.61) and 0.86 (95% CI: 0.71-0.94). CONCLUSIONS: The NSE concentration of patients with poor coma prognosis is significantly higher than that of the control group. The high NSE concentration is not necessarily a poor prognosis for coma, but low NSE concentration indicates a high probability of a good prognosis for coma.

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.

The Glucagon-Like Peptide-1 Analog Exenatide Increases Blood Glucose Clearance, Lactate Clearance, and Heart Rate in Comatose Patients After Out-of-Hospital Cardiac Arrest.

OBJECTIVES: To investigate the effects of the glucagon-like peptide-1 analog exenatide on blood glucose, lactate clearance, and hemodynamic variables in comatose, resuscitated out-of-hospital cardiac arrest patients. DESIGN: Predefined post hoc analyzes from a double-blind, randomized clinical trial. SETTING: The ICU of a tertiary heart center. PATIENTS: Consecutive sample of adult, comatose patients undergoing targeted temperature management after out-of-hospital cardiac arrest from a presumed cardiac cause, irrespective of the initial cardiac rhythm. INTERVENTIONS: Patients were randomized 1:1 to receive 6 hours and 15 minutes of infusion of either 17.4 µg of the glucagon-like peptide-1 analog exenatide (Byetta; Lilly) or placebo within 4 hours from sustained return of spontaneous circulation. The effects of exenatide were examined on the following prespecified covariates within the first 6 hours from study drug initiation: lactate level, blood glucose level, heart rate, mean arterial pressure, and combined dosage of norepinephrine and dopamine. MEASUREMENTS AND MAIN RESULTS: The population consisted of 106 patients receiving either exenatide or placebo. During the first 6 hours from study drug initiation, the levels of blood glucose and lactate decreased 17% (95% CI, 8.9-25%; p = 0.0004) and 21% (95% CI, 6.0-33%; p = 0.02) faster in patients receiving exenatide versus placebo, respectively. Exenatide increased heart rate by approximately 10 beats per minute compared to placebo (p < 0.0001). There was no effect of exenatide on other hemodynamic variables. CONCLUSIONS: In comatose out-of-hospital cardiac arrest patients, infusion with exenatide lowered blood glucose and resulted in increased clearance of lactate as well as increased heart rate. The clinical importance of these physiologic effects remains to be investigated.

Early prediction of coma recovery after cardiac arrest with blinded pupillometry.

OBJECTIVE: Prognostication studies on comatose cardiac arrest (CA) patients are limited by lack of blinding, potentially causing overestimation of outcome predictors and self-fulfilling prophecy. Using a blinded approach, we analyzed the value of quantitative automated pupillometry to predict neurological recovery after CA. METHODS: We examined a prospective cohort of 103 comatose adult patients who were unconscious 48 hours after CA and underwent repeated measurements of quantitative pupillary light reflex (PLR) using the Neurolight-Algiscan device. Clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEP), and serum neuron-specific enolase were performed in parallel, as part of standard multimodal assessment. Automated pupillometry results were blinded to clinicians involved in patient care. Cerebral Performance Categories (CPC) at 1 year was the outcome endpoint. RESULTS: Survivors (n = 50 patients; 32 CPC 1, 16 CPC 2, 2 CPC 3) had higher quantitative PLR (median = 20 [range = 13-41] vs 11 [0-55] %, p < 0.0001) and constriction velocity (1.46 [0.85-4.63] vs 0.94 [0.16-4.97] mm/s, p < 0.0001) than nonsurvivors. At 48 hours, a quantitative PLR < 13% had 100% specificity and positive predictive value to predict poor recovery (0% false-positive rate), and provided equal performance to that of EEG and SSEP. Reduced quantitative PLR correlated with higher serum neuron-specific enolase (Spearman r = -0.52, p < 0.0001). INTERPRETATION: Reduced quantitative PLR correlates with postanoxic brain injury and, when compared to standard multimodal assessment, is highly accurate in predicting long-term prognosis after CA. This is the first prognostication study to show the value of automated pupillometry using a blinded approach to minimize self-fulfilling prophecy. Ann Neurol 2017;81:804-810.

Characteristics of jugular bulb oxygen saturation in patients after cardiac arrest: A prospective study.

BACKGROUND: Using cerebral oxygen venous saturation post-cardiac arrest (CA) is limited because of a small sample size and prior to establishment of target temperature management (TTM). We aimed to describe variations in jugular bulb oxygen saturation during intensive care in relation to neurological outcome at 6 months post- CA in cases where TTM 33°C was applied. METHOD: Prospective observational study in patients over 18 years, comatose immediately after resuscitation from CA. Patients were treated with TTM 33°C M and received a jugular bulb catheter within the first 26 hours post-CA. Neurological outcome was assessed at 6 months using the Cerebral Performance Categories (CPC) and dichotomized into good (CPC 1-2) and poor outcome (CPC 3-5). RESULTS: Seventy-five patients were included and 37 (49%) patients survived with a good outcome at 6 months post-CA. No differences were found between patients with good outcome and poor outcome in jugular bulb oxygen saturation. Higher values were seen in differences in oxygen content between central venous oxygen saturation and jugular bulb oxygen saturation in patients with good outcome compared to patients with poor outcome at 6 hours (12 [8-21] vs 5 [-0.3 to 11]% P = .001) post-CA. Oxygen extraction fraction from the brain illustrated lower values in patients with poor outcome compared to patients with good outcome at 96 hours (14 [9-23] vs 31 [25-34]% P = .008). CONCLUSIONS: Oxygen delivery and extraction differed in patients with a good outcome compared to those with a poor outcome at single time points. Based on the present findings, the usefulness of jugular bulb oxygen saturation for prognostic purposes is uncertain in patients treated with TTM 33°C post-CA.

Acute Kidney Injury as a Risk Factor for Delirium and Coma during Critical Illness.

RATIONALE: Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma. OBJECTIVES: To examine whether acute kidney injury is associated with delirium and coma in critically ill adults. METHODS: In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale. MEASUREMENTS AND MAIN RESULTS: Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.07-2.26) and coma (OR, 2.04; 95% CI, 1.25-3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57-4.16) (OR for coma, 3.34; 95% CI, 1.85-6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18-1.55) and coma (OR, 1.44; 95% CI, 1.20-1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma. CONCLUSIONS: Acute kidney injury is a risk factor for delirium and coma during critical illness.

Doege-Potter syndrome: hypoglycaemic coma in a 90-year old due to a solitary fibrous tumour.

Solitary fibrous tumour of the pleura (SFTP) is a rare primary tumour of the pleura associated with 4% of cases with a paraneoplastic hypoglycaemia, termed Doege-Potter syndrome (DPS). We report a case of DPS presenting with severe coma in a 90-year-old woman. The cause was a malignant SFTP treated with surgical resection, from which the patient made a full recovery with prevention of recurrent hypoglycaemia. Surgical resection of the SFTP presenting with symptomatic hypoglycaemia should be considered even in elderly patients.

[Hypercalcemic crisis and hypocalcemic tetany]. / Hyperkalzämische Krise und hypokalzämische Tetanie.

A serum calcium level >3.5 mmol/l together with clinical symptoms such as muscle weakness, fatigue, nausea, vomiting, pancreatitis or even coma are characteristic for a hypercalcemic crisis (HC). Primary hyperparathyroidism (1HPT) and malignancy-associated hypercalcemia are the most frequent causal diseases for a HC. The analysis of serum levels for calcium, phosphorous, intact parathyroid hormone, electrophoresis and renal function parameters indicate which further radiological, scintigraphic or serum diagnostic steps are adequate to identify the cause of the patient's acute situation (i. e. most frequently 1HPT or malignant disease with bone involvement, e. g. myeloma) and thus to initiate the required surgical or oncological intervention. However, the primary goals in the treatment of HC include correcting dehydration and improving kidney function, lowering calcium levels and decreasing osteoclastic bone resorption. The goals are accomplished by volume repletion, forced diuresis, antiresorptive agents and hemodialysis on an intensive care unit. Hypocalcemic tetany (HT) is the consequence of severely lowered calcium levels (<2.0 mmol/l), usually in patients with chronic hypocalcemia. The causal disease for hypocalcemic tetany is frequently a lack of parathyroid hormone (PTH), (e. g. as a complication of thyroid surgery) or, rarely, resistance to PTH. HT due to severe and painful clinical symptoms requires rapid i. v. calcium replacement by central venous catheter on an intensive care unit. For the treatment of chronic hypocalcemia oral calcium and 25OH-vitamin D or even 1,25(OH)2-vitamin D3 and magnesium supplements may be necessary to achieve the desired low normal calcium levels. Thiazides are useful to reduce renal calcium loss and to stabilize the calcium levels. Some patients continue to exhibit clinical symptoms despite adequate calcium levels; in these cases s. c. parathyroid hormone 1-84 should be considered to stabilize calcium levels and to lower the dosage of calcium and vitamin D supplements.

Hyperoxia Early After Hospital Admission in Comatose Patients with Non-Traumatic Out-of-Hospital Cardiac Arrest.

BACKGROUND The clinical effect of hyperoxia in patients with non-traumatic out-of-hospital cardiac arrest (OHCA) remains uncertain. We therefore initiated this study to find out whether there is an association between survival and hyperoxia early after return of spontaneous circulation (ROSC) in OHCA patients admitted to our hospital. MATERIAL AND METHODS All OHCA patients admitted to our hospital between 1 January 2008 and 30 June 2015 were identified by analysis of our central admission register. Data from individual patients were collected from patient health records and anonymously stored on a central database. RESULTS Altogether, there were 280 OHCA patients admitted to our hospital between 1 January 2008 and 30 June 2015, including 35 patients (12.5%) with hyperoxia and 99 patients (35.4%) with normoxia. Comparison of these 2 groups showed lower pH values in OHCA patients admitted with normoxia compared to those with hyperoxia (7.10±0.18 vs. 7.21±0.17; p=0.001) but similar rates of initial lactate (7.92±3.87 mmol/l vs. 11.14±16.40 mmol/l; p=0.072). Survival rates differed between both groups (34.4% vs. 54.3%; p=0.038) with better survival rates in OHCA patients with hyperoxia at hospital admission. CONCLUSIONS Currently, different criteria are used to define hyperoxia following OHCA, but if the negative effects of hyperoxia in OHCA patients are a cumulative effect over time, hyperoxia < 60 min after hospital admission as investigated in this study would be equivalent to a short period of hyperoxia. It may be that the positive effect of buffering metabolic acidosis early after cardiac arrest maintains the negative effects of hyperoxia in general.

Severe Carbamazepine Intoxication in Children: Analysis of a 40-Case Series.

BACKGROUND We compared the factors that might impact the severity and the prognosis of carbamazepine (CBZ) intoxication in children, as well as the efficacy levels of the treatment options. MATERIAL AND METHODS Demographic information and clinical and laboratory findings for 40 patients were evaluated retrospectively. Predictive parameters for the development of serious complications were studied. RESULTS Median age of patients was 14 years; 65% of the patients were female. The most common pathological clinical finding and laboratory abnormality were inability to awaken the patient and hyperglycemia (45% and 60%, respectively). The incidences of convulsion, coma, and respiratory failure were 14 (35%), 10 (25%), and 3 (7.5%), respectively. The Glasgow Coma Scale (GCS) scores and pH levels at emergency service admission were significantly lower in the severe intoxication group and the ICU admission group, and body temperature and serum glucose and lactate levels were significantly higher in these groups. A significantly negative correlation was found between the serum CBZ level and the GCS score, but the serum CBZ level was found to be significantly positively correlated with the lactate level. CONCLUSIONS According to our study, the GCS score at admission to hospital, the serum CBZ, glucose, pH, and lactate levels, and body temperature might be useful in predicting serious CBZ intoxication and prognosis in pediatric cases. We conclude that invasive treatment methods, such as hemodialysis or albumin-enhanced continuous venovenous hemodialysis, should be used in patients who do not respond to supportive treatment.

Increased Thyroxin During Therapeutic Hypothermia Predicts Death in Comatose Patients After Cardiac Arrest.

BACKGROUND: The course and prognostic value of pituitary-thyroid axis hormones is not well studied after cardiac arrest. We aimed to study the prognostic role of the pituitary-thyroid axis response to resuscitation from cardiac arrest before, during and after therapeutic hypothermia. METHODS: We conducted a retrospective cohort study in consecutive comatose patients after out-of-hospital cardiac arrest who were sampled before, during and up to 48 h after a 24-h period of therapeutic hypothermia in the intensive care unit (ICU). Thyroid-stimulating hormone, total and free thyroxine (T4) and triiodothyronine (T3) were determined and compared between ICU outcome groups. RESULTS: We included twenty-nine patients. TSH levels were comparable in non-survivors (n = 17) and survivors (n = 12). The free T4 levels were higher in non-survivors than in survivors (P = 0.001), whereas the free T3 levels were comparable. All samples' results similarly declined in both outcome groups up to 72 h after start of 24 h hypothermia. ROC curves analyses showed a maximum AUC of 0.83 (P = 0.003) for free T4 at the end of hypothermia with an optimal cut off ≥17.8 pmol/L to obtain 100 % specificity and positive predictive value for non-survival. CONCLUSION: Non-survival after cardiac arrest, coma, and therapeutic hypothermia following successful resuscitation is associated with a transient increase in free T4, most probably due to inhibition of free T4 to T3 conversion. However, before routine clinical application, external validation of our finding to assess generalizability is warranted.

Effects of viscosity on cerebral blood flow after cardiac arrest.

OBJECTIVES: To determine blood viscosity in adult comatose patients treated with mild therapeutic hypothermia after cardiac arrest and to assess the relation between blood viscosity, cerebral blood flow, and cerebral oxygen extraction. DESIGN: Observational study. SETTING: Tertiary care university hospital. PATIENTS: Ten comatose patients with return of spontaneous circulation after out-of-hospital cardiac arrest. INTERVENTION: Treatment with mild therapeutic hypothermia for 24 hours followed by passive rewarming to normothermia. MEASUREMENTS AND MAIN RESULTS: Median viscosity at shear rate 50/s was 5.27 mPa · s (4.29-5.91 mPa · s) at admission; it remained relatively stable during the first 12 hours and decreased significantly to 3.00 mPa · s (2.72-3.58 mPa · s) at 72 hours (p < 0.001). Median mean flow velocity in the middle cerebral artery was low (27.0 cm/s [23.8-30.5 cm/s]) at admission and significantly increased to 63.0 cm/s (51.0-80.0 cm/s) at 72 hours. Median jugular bulb saturation at the start of the study was 61.5% (55.5-75.3%) and significantly increased to 73.0% (69.0-81.0%) at 72 hours. Median hematocrit was 0.41 L/L (0.36-0.44 L/L) at admission and subsequently decreased significantly to 0.32 L/L (0.27-0.35 L/L) at 72 hours. Median C-reactive protein concentration was low at admission (2.5 mg/L [2.5-6.5 mg/L]) and increased to 101 mg/L (65-113.3 mg/L) in the following hours. Median fibrinogen concentration was increased at admission 2,795 mg/L (2,503-3,565 mg/L) and subsequently further increased to 6,195 mg/L (5,843-7,368 mg/L) at 72 hours. There was a significant negative association between blood viscosity and the mean flow velocity in the middle cerebral artery (p = 0.0008). CONCLUSIONS: Changes in blood viscosity in vivo are associated with changes in flow velocity in the middle cerebral artery. High viscosity early after cardiac arrest may reduce cerebral blood flow and may contribute to secondary brain injury. Further studies are needed to determine the optimal viscosity during the different stages of the postcardiac arrest syndrome.

[Circadian clock genes expression in peripheral blood mononuclear cells of comatose patients]. / Expression des genes de l'horloge circadienne dans les cellules sanguines mononuclées chez des comateux.

BACKGROUND: Recently circadian clock genes have been identified in humans but information regarding their expression has remained very limited. The evaluation of circadian variations in the expression of clock genes in humans seems to be a major importance both from a fundamental point of view as a diagnostic and therapeutic perspective. In this context, several works including ours have described the fluctuation of clock genes. AIMS: describing rhythmic expression of clock genes in intensive care units patients during 24h and we tried to determine the effect of the absence of synchronizers such as light/ dark cycle on these rhythms. METHODS: 15 patients received care in private room in intensive care units in the hospital Sahloul (5 comatous and 10 non comatous patients). For RNA isolation we used peripheral blood mononuclear cells which represent an ideal material to investigate non-invasively the human clock at the molecular level. RESULTS: In the present study, we noticed that clock genes mRNA exhibit a circadian expression in comatose patients, while the rhythmicity of some studied genes disappeared in non-comatose patients. CONCLUSION: The disturbance of the rhythmic fluctuation of the clock genes could be the result of the effect of surgery on some biological rhythms as it could be explained by the lack of synchronizers in intensive care units such as light/dark cycle.

Association between the red cell distribution width and mortality in elderly patients with non-traumatic coma: An observational cohort study.

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.

Systemic inflammation and delirium during critical illness.

PURPOSE: The purpose of this study was to determine associations between markers of inflammation and endogenous anticoagulant activity with delirium and coma during critical illness. METHODS: In this prospective cohort study, we enrolled adults with respiratory failure and/or shock treated in medical or surgical intensive care units (ICUs) at 5 centers. Twice per day in the ICU, and daily thereafter, we assessed mental status using the Richmond Agitation Sedation Scale (RASS) and the Confusion Assessment Method-Intensive Care Unit (CAM-ICU). We collected blood samples on study days 1, 3, and 5, measuring levels of C-reactive protein (CRP), interferon gamma (IFN-γ), interleukin (IL)-1 beta (IL-1ß), IL-6, IL-8, IL-10, IL-12, matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 1 (TNFR1), and protein C using validated protocols. We used multinomial logistic regression to analyze associations between biomarkers and the odds of delirium or coma versus normal mental status the following day, adjusting for age, sepsis, Sequential Organ Failure Assessment (SOFA), study day, corticosteroids, and sedatives. RESULTS: Among 991 participants with a median age (interquartile range, IQR) of 62 [53-72] years and enrollment SOFA of 9 [7-11], higher concentrations of IL-6 (odds ratio [OR] [95% CI]: 1.8 [1.4-2.3]), IL-8 (1.3 [1.1-1.5]), IL-10 (1.5 [1.2-1.8]), TNF-α (1.2 [1.0-1.4]), and TNFR1 (1.3 [1.1-1.6]) and lower concentrations of protein C (0.7 [0.6-0.8])) were associated with delirium the following day. Higher concentrations of CRP (1.4 [1.1-1.7]), IFN-γ (1.3 [1.1-1.5]), IL-6 (2.3 [1.8-3.0]), IL-8 (1.8 [1.4-2.3]), and IL-10 (1.5 [1.2-2.0]) and lower concentrations of protein C (0.6 [0.5-0.8]) were associated with coma the following day. IL-1ß, IL-12, and MMP-9 were not associated with mental status. CONCLUSION: Markers of inflammation and possibly endogenous anticoagulant activity are associated with delirium and coma during critical illness.

Improvements in hepatic serological biomarkers are associated with clinical benefit of intravenous N-acetylcysteine in early stage non-acetaminophen acute liver failure.

BACKGROUND: N-acetylcysteine (NAC) improves transplant-free survival in early coma grade (I-II) patients with non-acetaminophen induced acute liver failure (ALF). We determined whether the clinical benefit was associated with improvements in hepatic function. METHODS: In a prospective, double blind trial, 173 ALF patients without evidence of acetaminophen overdose were stratified by coma grade (I-II vs. III-IV) and randomly assigned to receive either intravenous NAC or dextrose (placebo) for 72 h, resulting in four patient groups. INR, ALT, bilirubin, creatinine, and AST obtained on admission (day 1) and subsequent days (days 2-4) were used for secondary analysis performed by fitting longitudinal logistic regression models to predict death or transplantation or transplantation alone. RESULTS: Treatment group and day of study in models including bilirubin or ALT were predictors of transplantation or death (maximum p < 0.03). Those patients with early coma grade who were treated with NAC showed significant improvement in bilirubin and ALT levels when compared to the other three groups (maximum p < 0.02 for NAC 1-2 vs. the 3 other treatments) when predicting death or transplantation. Treatment group, day of study, and bilirubin were predictors of transplantation (maximum p < 0.03) in ALF patients. CONCLUSION: The decreased risk of transplantation or death or of transplantation alone with intravenous NAC in early coma grade patients with non-acetaminophen induced ALF was reflected in improvement in parameters related to hepatocyte necrosis and bile excretion including ALT and bilirubin, but not in INR, creatinine, or AST. Hepatic recovery appears hastened by NAC as measured by several important lab values.

Association of blood glucose variability with outcomes in comatose cardiac arrest survivors treated with therapeutic hypothermia.

PURPOSE: A recent study showed that increased blood glucose variability was an independent predictor of mortality in cardiac arrest survivors treated with therapeutic hypothermia (TH). We hypothesized that the association of blood glucose variability with outcomes would differ depending on the TH phase, as body temperature affects glucose homeostasis. METHODS: A retrospective cohort of 147 consecutive cardiac arrest patients treated with TH was analyzed. Mean absolute glucose change (MAGC) was calculated using blood glucose values during the entire TH period and during each TH phase (induction, from the TH initiation to the achievement of the target temperature; maintenance, 24 hours from the end of induction; and rewarming, from the end of the maintenance to the achievement of 36.5°C). The primary and secondary outcomes were mortality and neurological outcome at 30 days. Multivariate regression analyses were performed with variables with a significance level <0.1 on univariate analyses. RESULTS: The hypoglycemia rate increased significantly during the rewarming phase compared with the maintenance phase (P = .003). The MAGC during the TH maintenance phase was an independent predictor of mortality (OR = 1.056, 95% CI 1.008-1.107, P = .023) and unfavorable neurologic outcome (OR = 1.202, 95% CI 1.043-1.384, P = .038), while the MAGC during the rewarming phase and the entire TH period were not. CONCLUSION: The increased MAGC during the TH maintenance phase was associated with mortality and unfavorable neurologic outcome. However, this study cannot prove a causal association due to the retrospective design. In addition, we showed that the hypoglycemia rate increased significantly during the rewarming phase.