Depressed Level Of Consciousness Research Articles

Carbon dioxide insufflation during colorectal endoscopic submucosal dissection for patients with obstructive ventilatory disturbance

Carbon dioxide (CO(2)) insufflation reduces abdominal pain and discomfort after endoscopic procedures; however, there is no previous study focusing the safety of CO(2) insufflation for patients with obstructive ventilatory disturbance. Here, we investigated the safety of CO(2) insufflation during colorectal endoscopic submucosal dissection (ESD) for patients with obstructive disturbance. Between January 2010 and January 2013, colorectal ESD was performed using CO(2) insufflation for 385 consecutive patients. End-tidal CO(2) (EtCO(2)) and transcutaneous oxygen saturation (SpO(2)) were consecutively measured from the time before insertion of the colonoscope to the end of ESD. Patients were monitored by two nurses during the procedure and controlled for clinical symptoms of hypercapnia such as apnea or a depressed level of consciousness. According to their respiratory function, patients were stratified into a normal group and an obstructive disturbance group. We retrospectively compared EtCO(2) and SpO(2) during the procedures and the incidence of symptoms related to CO(2) retention between the two groups. The obstructive disturbance group consisted of 77 patients. There were similar changes of EtCO(2) in the obstructive disturbance group and normal group and no significant rise in EtCO(2). The maximum EtCO(2) level in any patient was <60 mmHg. In the obstructive disturbance group, there were no symptoms associated with CO(2) retention. There were no significant differences in the median SpO(2) between both groups and no prolonged drop of SpO(2). CO(2) insufflation during colorectal ESD is safe for patients with obstructive ventilatory disturbance.

Improved outcome of patients with severe thalamic hemorrhage treated with cerebrospinal fluid drainage and neurocritical care during 1990–1994 and 2005–2009

Patients with thalamic hemorrhage, depressed level of consciousness and/or signs of elevated intracranial pressure may be treated with neurocritical care (NCC) and external ventricular drainage (EVD) for release of cerebrospinal fluid. Forty-three patients with thalamic hemorrhage treated with NCC from 1990 to 1994 (n = 21) and from 2005-2009 (n = 22) were evaluated. Outcome was assessed using the Glasgow Coma Scale (GCS) score at discharge from our unit and the modified Rankin Scale (mRS) for long-term outcome. Patients' age was 59.5 ± 7 years in 1990-1994, and 58.2 ± 9 years in 2005-2009. The median (25th and 75th percentile) GCS score on admission for the two time periods was 9 (6-12) and 9 (4-14), respectively. Long-term follow-up was assessed at a mean of 37.1 (range 19-65) months after disease onset for the 1990-1994 cohort and at 37.4 (range 14-58) months for the 2005-2009 cohort. Compared to patients from 1990 to 1994, patients from 2005 to 2009 had a significantly better outcome (median mRS [25th and 75th percentile]: 5 [4-6] vs. 4 [2-4.5]; p < 0.01). Most patients (13/21, 62 %) treated from 1990 to 1994 had unchanged or lower GCS scores during their NCC stay in contrast to 7/22 (32 %) from 2005 to 2009. At the last follow-up, 13/21 (62 %) patients from 1990 to 1994 were dead in comparison to 4/21 (19 %) from 2005 to 2009 (p < 0.05). Negative prognostic factors were the 120 h post-admission GCS score in the 1990-1994 patient cohort (p = 0.07) and high age in the recent cohort (p = 0.04). Patients with thalamic hemorrhage and depressed level of consciousness on admission had a worse outcome in the early 1990s compared with the late 2000s, which may at least be partially attributed to refined neurocritical care.

Cervical spine clearance in the traumatically injured patient: is multidetector CT scanning sufficient alone?

Clearance of the cervical spine in patients who have sustained trauma remains a contentious issue. Clinical examination alone is sufficient in neurologically intact patients without neck pain. Patients with neck pain or those with altered mental status or a depressed level of consciousness require further radiographic evaluation. However, no consensus exists as to the appropriate imaging modality. Some advocate multidetector CT (MDCT) scanning alone, but this has been criticized because MDCT is not sensitive in detecting ligamentous injuries that can often only be identified on MRI. Patients were identified retrospectively from a prospectively maintained database at a Level I trauma center. All patients admitted between January 2004 and June 2011 who had a cervical MDCT scan interpreted by a board-certified radiologist as being without evidence of acute traumatic injury and who also had a cervical MRI study obtained during the same hospital admission were included. Data collected included patient demographics, mechanism of injury, Glasgow Coma Scale score at the time of MRI, the indication for and findings on MRI, and the number, type, and indication for cervical spine procedures. A total of 1004 patients were reviewed, of whom 614 were male, with an overall mean age of 47 years. The indication for MRI was neck pain in 662 patients, altered mental status in 467, and neurological signs or symptoms in 157. The MRI studies were interpreted as normal in 645 patients, evidencing ligamentous injury alone in 125, and showing nonspecific degenerative changes in the remaining patients. Of the 125 patients with ligamentous injuries, 66 (52.8%) had documentation of clearance (29 clinical, 37 with flexion-extension radiographs). Another 32 patients were presumed to be self-cleared, bringing the follow-up rate to 82% (98 of 119). Five patients died prior to clearance, and 1 patient was transferred to another facility prior to clearance. Based on these data, the 95% confidence interval for the assertion that clinically irrelevant ligamentous injury in the face of normal MDCT is 97%-100%. No patient with ligamentous injury on MRI was documented to require a surgical procedure or halo orthosis for instability. Thirty-nine patients ultimately underwent cervical surgical procedures (29 anterior and 10 posterior; 5 delayed) for central cord syndrome (21), quadriparesis (9), or discogenic radicular pain (9). None had an unstable spine. In this study population, MRI did not add any additional information beyond MDCT in identifying unstable cervical spine injuries. Magnetic resonance imaging frequently detected ligamentous injuries, none of which were found to be unstable at the time of detection, during the course of admission, or on follow-up. Magnetic resonance imaging provided beneficial clinical information and guided surgical procedures in patients with neurological deficits or radicular pain. An MDCT study with sagittal and coronal reconstructions negative for acute injury in patients without an abnormal motor examination may be sufficient alone for clearance.

Sedation level and prevalence of delirium: response to Brummel and Ely

Dear Editor, We thank Dr. Brummel and his team [1] for their interest in our paper [2]. We agree that the prevalence of delirium in awake ICU patients in our study is similar to that found in earlier studies (42.5 % in the study by Ely et al. [3], 31 % in our study). However, we propose that reports on delirium should be stratified for a sedation score during the assessment, because the apparent prevalence of delirium is dependent on how a depressed level of consciousness after sedation stop is interpreted. For instance, of 471 daily evaluations completed during the study by Ely et al. [3], a diagnosis by the reference standard of delirium was made in 25.2 %, stupor in 21.3 %, and coma in 28.5 % of all observations. Yet, the authors report that delirium occurred in 83.3 % of their patients. Unfortunately, in the validation studies neither CAM-ICU nor ICDSC described how sedated patients were handled. The new DSM-V criteria for delirium published recently indicate that non-comatose patients with a reduced level of arousal of acute onset should be classified as having severe inattention and cognitive change, and hence delirium. We agree that such patients can be delirious. Nevertheless, it should be noted that the same criteria—which correspond to a RASS-2/-3 level—can also apply for sedated healthy volunteers, and patients with uneventful postoperative course during awakening from anesthesia. By no means do we suggest that delirium should not be considered in sedated patients. However, we question the specificity of the assessments tools CAM-ICU and ICDSC in sedated patients who cannot hold eye contact for 10 s. In contrast to what has been proposed for the CAM-ICU [4], we suggest to use the delirium assessment tools after sedation stop, and to indicate the level of consciousness during the assessment. An exclusive diagnosis of delirium is impossible before effects of sedation are ruled out. Regular sedation stops have been proven to improve outcome and reduce resource use. We should make every effort not to miss a diagnosis of delirium. At the same time, misdiagnosing persistent sedation as delirium is dangerous as well: a recent delirium trial was prematurely stopped because of increased mortality in the treatment group [5]. In this study, almost 40 % of the included patients had a negative RASS, half of them a RASS of -2. In our view, sedation should be managed with a protocolized approach including a sedation goal and frequent assessments, and not with a delirium screening tool.

Effect of sedation level on the prevalence of delirium when assessed with CAM-ICU and ICDSC

We hypothesized that reduced arousability (Richmond Agitation Sedation Scale, RASS, scores -2 to -3) for any reason during delirium assessment increases the apparent prevalence of delirium in intensive care patients. To test this hypothesis, we assessed delirium using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Intensive Care Delirium Screening Checklist (ICDSC) in intensive care patients during sedation stops, and related the findings to the level of sedation, as assessed with RASS score. We assessed delirium in 80 patients with ICU stay longer than 48 h using CAM-ICU and ICDSC during daily sedation stops. Sedation was assessed using RASS. The effect of including patients with a RASS of -2 and -3 during sedation stop ("light to moderate sedation", eye contact less than 10 s or not at all, respectively) on prevalence of delirium was analyzed. A total of 467 patient days were assessed. The proportion of CAM-ICU-positive evaluations decreased from 53 to 31 % (p < 0.001) if assessments from patients at RASS -2/-3 (22 % of all assessments) were excluded. Similarly, the number of positive ICDSC results decreased from 51 to 29 % (p < 0.001). Sedation per se can result in positive items of both CAM-ICU and ICDSC, and therefore in a diagnosis of delirium. Consequently, apparent prevalence of delirium is dependent on how a depressed level of consciousness after sedation stop is interpreted (delirium vs persisting sedation). We suggest that any reports on delirium using these assessment tools should be stratified for a sedation score during the assessment.

Toxicity Following Laundry Detergent Pod Ingestion

Laundry detergent pods (LDPs) have only recently become available in the United States, and there has been increasing concern regarding pediatric ingestions of them. We describe a 15-month-old female infant who ingested an LDP and had a depressed level of consciousness, metabolic acidosis, pulmonary toxicity, and swallowing difficulties. It is currently unclear what the exact etiologic agent(s) is responsible for the toxicity associated with LDPs. The case demonstrates the potential for significant toxicity following the ingestion of an LDP. Clearly, measures should be taken to avoid ingestions of these products.

Inability to self-report pain after a stroke: A population-based study

The frequency of not being able to self-report pain after a stroke has not been previously assessed in a population-based sample. We studied the epidemiology of this problem using a cohort of patients hospitalized after a stroke in Olmsted County, Minnesota, from June 1, 2008, to June 1, 2012. Overall, 52 of 388 (13.4%) individuals were unable to provide a meaningful response to either a Faces Pain Scale or Numerical Rating Scale on admission. Inability to self-report pain was associated with measures of stroke severity (P<.0001), aphasia severity (P<.0001), and level of consciousness (P<.0001). Inability to self-report pain on admission was further associated with either subsequent death during the hospitalization (P<.0001) or an inability to provide self-report on dismissal (P<.0001). Our study further defines the epidemiology of the inability to self-report pain after a stroke as being less common than previously thought. Attempts to validate observational pain scales for poststroke patients should focus on those individuals with aphasia and/or depressed levels of consciousness.

Effect of Sedation on Pain Perception

Sedation or anesthesia is used to facilitate many cases of an estimated 45 million diagnostic and therapeutic medical procedures in the United States. Preclinical studies have called attention to the possibility that sedative-hypnotic drugs can increase pain perception, but whether this observation holds true in humans and whether pain-modulating effects are agent-specific or characteristic of IV sedation in general remain unclear. To study this important clinical question, the authors recruited 86 healthy volunteers and randomly assigned them to receive one of three sedative drugs: midazolam, propofol, or dexmedetomidine. The authors asked participants to rate their pain in response to four experimental pain tasks (i.e., cold, heat, ischemic, or electrical pain) before and during moderate sedation. Midazolam increased cold, heat, and electrical pain perception significantly (10-point pain rating scale change, 0.82 ± 0.29, mean ± SEM). Propofol reduced ischemic pain and dexmedetomidine reduced both cold and ischemic pain significantly (-1.58 ± 0.28, mean ± SEM). The authors observed a gender-by-race interaction for dexmedetomidine. In addition to these drug-specific effects, the authors observed gender effects on pain perception; female subjects rated identical experimental pain stimuli higher than male subjects. The authors also noted race-drug interaction effects for dexmedetomidine, with higher doses of drug needed to sedate Caucasians compared with African Americans. The results of the authors' study call attention to the fact that IV sedatives may increase pain perception. The effect of sedation on pain perception is agent- and pain type-specific. Knowledge of these effects provides a rational basis for analgesia and sedation to facilitate medical procedures.

Safety of midazolam for sedation of HIV‐positive patients undergoing colonoscopy

Because of concerns regarding interactions between midazolam and antiretroviral therapy (ART), alternative sedatives are sometimes used during procedural sedation. Our objective was to compare outcomes in patients on ART who received intravenous (iv) midazolam vs. iv diazepam, a second-line agent, during colonoscopy. We conducted a retrospective analysis of adult HIV-positive patients who underwent colonoscopy over a 3.5-year period. Primary outcomes were sedation duration, nadir systolic blood pressure (SBP), nadir oxygen saturation, abnormal cardiac rhythm, and change in level of consciousness using a standardized scale. We calculated rates of adverse events according to benzodiazepine use and identified risk factors for complications using univariate and multivariate analyses. We identified 136 patients for this analysis: 70 received midazolam-based sedation and 66 received a diazepam-based regimen. There were no significant differences between the two groups with respect to sedation duration (mean 48.0 vs. 45.7 minutes for the midazolam and diazepam groups, respectively; P = 0.68), nadir SBP (mean 97.0 vs. 101.6 mmHg; P = 0.06), nadir oxygen saturation (mean 94.6 vs. 94.8%; P = 0.72) or rate of abnormal cardiac rhythm (11.4 vs. 19.7%; P = 0.18). More patients in the midazolam group experienced a depressed level of consciousness (91% vs. 74% in the diazepam group; P = 0.0075), but no patient required reversal of sedation or became unresponsive. We did not find evidence that patients who received midazolam for procedural sedation had clinical outcomes statistically different from those who received diazepam. These findings should be confirmed in prospective studies or in a randomized controlled trial.

A rare cause of neonatal hydrocephalus

AbstractA term male infant was delivered by normal vaginal delivery following an uneventful pregnancy. He presented at 3 days of age with jaundice, weight loss, and poor feeding. He rapidly deteriorated with hypotonia, seizures, a tense fontanelle, and depressed conscious level. A cranial ultrasound scan showed moderate lateral and third ventricular dilatation, with no visible fourth ventricle. Doppler measurements showed absent diastolic flow, confirming markedly raised intracranial pressure. Cerebrospinal fluid pressure was markedly elevated and coagulation profile showed a specific prolongation of the activated partial thromboplastin time. Factor VIII assay confirmed haemophilia and a computed tomography scan showed a posterior fossa haemorrhage that was effacing the fourth ventricle and causing an acute hydrocephalus. He was managed with cerebrospinal fluid drainage and recombinant factor VIII concentrate. Posterior fossa haemorrhage is an unusual cause of acute high pressure hydrocephalus in the term neonate. Haemophilia should be considered as a cause of unusual intracranial haemorrhage in term neonates.

A prospective cohort study of stroke characteristics, care, and mortality in a hospital stroke registry in Vietnam.

BackgroundAs low and middle-income countries such as Vietnam experience the health transition from infectious to chronic diseases, the morbidity and mortality from stroke will rise. In line with the recommendation of the Institute of Medicine’s report on “Promoting Cardiovascular Health in the Developing World” to “improve local data”, we sought to investigate patient characteristics and clinical predictors of mortality among stroke inpatients at Da Nang Hospital in Vietnam.MethodsA stroke registry was developed and implemented at Da Nang Hospital utilizing the World Health Organization’s Stroke STEPS instrument for data collection.Results754 patients were hospitalized for stroke from March 2010 through February 2011 and admitted to either the intensive care unit or cardiology ward. Mean age was 65 years, and 39% were female. Nearly 50% of strokes were hemorrhagic. At 28-day follow-up, 51.0% of patients with hemorrhagic stroke died whereas 20.3% of patients with ischemic stroke died. A number of factors were independently associated with 28-day mortality; the two strongest independent predictors were depressed level of consciousness on presentation and hemorrhagic stroke type. While virtually all patients completed a CT during the admission, evidence-based processes of care such as anti-thrombotic therapy and carotid ultrasound for ischemic stroke patients were underutilized.ConclusionsThis cohort study highlights the high mortality due in part to the large proportion of hemorrhagic strokes in Vietnam. Lack of hypertension awareness and standards of care exacerbated clinical outcomes. Numerous opportunities for simple, inexpensive interventions to improve outcomes or reduce recurrent stroke have been identified.

Results From the Phase II Dose Expansion of Cyclophosphamide, Carfilzomib, Thalidomide and Dexamethasone (CYCLONE) in Patients with Newly Diagnosed Multiple Myeloma

AbstractAbstract 445 Background:Carfilzomib is a proteasome inhibitor that irreversibly binds its target and has a favorable toxicity profile that has shown significant activity in relapsed multiple myeloma (MM), leading to recent FDA accelerated approval. To achieve rapid and deep response in patients eligible for stem cell transplant, we combined carfilzomib with the regimen of cyclophosphamide-thalidomide-dexamethasone (CTD). We recently reported the results of the Phase I component of the trial (in which no MTD was reached) followed by the initial Phase II trial; however, with increasing evidence for the safe and effective use of higher doses of carfilzomib, we now report results from dose escalation extension of the Phase II trial. Methods:Newly diagnosed myeloma patients intended for stem cell transplant were eligible. All patients were treated on a 28 day cycle with Carfilzomib IV Days 1,2,8,9,15,16 (see Table 1 below for dosing per cohort) along with Cyclophosphamide 300 mg/m2 PO Days 1,8,15, Thalidomide 100 mg PO Days 1–28 and Dexamethasone 40 mg PO Days 1,8,15,22.We initially conducted a Phase I run in trial of 6 patients with no DLT observed before expanding to the Phase II portion of the study. The initial phase II regimen is shown below – as no DLTs were observed, we have now fully accrued to the Phase II dose level +1. Treatment was for 4 cycles with expected SCT post induction. The primary endpoint of the trial is the proportion of patients who have ≥very good partial response (VGPR) to treatment. All patients received herpes zoster prophylaxis and ASA daily.Table 1:Dose Levels and Accrual for CYCLONEDose LevelNumberCycle 1Cycle 2 and beyond*-1 (initial Phase I)315 mg/m220 mg/m20 (initial Phase II - completed)3+ 21 = 2420 mg/m227 mg/m21 (completed, no DLTs)420 mg/m236 mg/m22 (accruing)720 mg/m245 mg/m2*At dose level 1 and 2, pts can initiate this dose starting on Day 8 of Cycle 1. Results:A total of 38 patients have been accrued to the trial, 6 in the initial Phase 1, 21 in the initial Phase II, and the remaining at dose escalated cohorts. We are reporting the 27 patients who have completed therapy and will update with the dose escalated cohorts. Median age was 65 (range 27–74) and 52% were female. ISS Stage was advanced (II-III) in 56%. Best overall response rate during 4 cycles of CYCLONE at dose level 0 is 96%: CR 29%, VGPR 46%, PR 21% (1 pt achieved MR).Adverse events of grade 3 or higher at least possibly related to CYCLONE occurred in 12 (44%). Most commonly reported non hematological toxicities (all grades) included fatigue (67%), constipation (56%), lethargy (41%) somnolence (37%), malaise (30%) depressed level of consciousness (22%); however, grade 3/4 toxicities occurring in >5% were uncommon: thromboembolic event 11%) and muscle weakness (7%). Two cases of pneumonia required hospitalization. Eight patients (30%) developed grade 1 sensory neuropathy; no higher grade or painful neuropathy was evident. There were no cardiac events seen in greater than 5% of patients. Grade 3/4 hematological toxicities included neutropenia (15%) and lymphopenia (7%). All patients advancing to SCT successfully collected stem cells. One patient died on study from pneumonia. Conclusion:The 4 drug CYCLONE regimen is highly efficaceous with a response rate after only 4 cycles of 96% (75% ≥VGPR, 29% CR) at the current dosing level of carfilzomib IV 20/27 mg/m2 in newly diagnosed myeloma. Toxicities are manageable, with only grade 1 neuropathy and minimal cardiac or pulmonary toxicity. Increasing the dose of carfilzomib is feasible and updated results of dose escalated cohorts will be reported at 20/36 and 20/45 mg/m2. Disclosures:Bergsagel:onyx: Membership on an entity's Board of Directors or advisory committees. Stewart:Millennium Pharmaceuticals: Consultancy, Honoraria, Research Funding; Onyx: Consultancy; Celgene: Consultancy.

Nosocomial myiasis in a patient with diabetes

This report describes a case of nosocomial myiasis caused by larvae of Sarcophaga (Bercaea) africa. The parasitosis developed in an ulcer on the heel of a patient with type 2 diabetes. The ulcer was dressed when the deposition occurred. An experiment was performed in order to demonstrate the ability of Sarcophaga larvae to move through bandages and reach purulent wounds. This report highlights the need for particular attention, education and specific protocols in hospitals in order to avoid myiasis, which can compromise the organization's reputation for hygienic standards with possible legal consequences.

Gender Differences in Patients with Intracerebral Hemorrhage: A Hospital-Based Multicenter Prospective Study

Gender differences are well described for patients with ischemic stroke. Conversely, sex disparities in stroke presentation, risk factors, treatment, and outcomes for intracerebral hemorrhage (ICH) were not previously studied. Our objective was to compare the frequency of risk factors, management patterns, symptoms at presentation, complication rates, and outcomes between genders in patients with ICH in Fortaleza, Brazil. Methods: Data were prospectively collected from patients admitted to 19 hospitals in Fortaleza with a diagnosis of ICH by trained research coordinators from June 2009 to October 2010. Daily visits to the selected hospitals were performed, and all patients admitted with a diagnosis of ICH were prospectively evaluated. Results: We evaluated 364 patients, 47.5% of whom were women. Men were younger (59.3 ± 14.58 years vs. 66.3 ± 14.6 years, p < 0.001), more frequently smokers (33.1 vs. 16.6%, p < 0.01) and had a higher frequency of alcohol abuse (48.5 vs. 8.2%, p < 0.01) than women. Women had a trend to have more dyslipidemia (41.1 vs. 31.3%, p = 0.12). Clinical presentation was similar between genders including the presence of motor and sensory deficits, headache, and depressed level of consciousness at presentation. Men had more speech disturbances than women (63.6 vs. 52.7%, p = 0.04). The time interval from symptoms onset to hospital admission was longer in women (25.1 ± 82.4 h vs. 7.9 ± 50.3 h, p = 0.08). Complication rates including pneumonia and deep vein thrombosis were not different between genders. Mortality was similar in both sexes (females: 35.8% vs. males: 33%, p = 0.66). Men were more frequently independent at discharge when evaluated by the modified Rankin Scale (mRS) score (mRS ≤2: 19.7% in men and 8.1% in women, p < 0.01). In the multivariate logistic regression analysis, older age, pre-stroke disability, depressed consciousness at admission, and female gender were independent predictors of poor outcome at discharge. Conclusion: Overall risk factors for ICH in men and women were similar in our series. Men had a higher frequency of alcohol abuse and smoking. Women were older, had an increased time length from symptoms onset to hospital admission and had a worse prognosis at discharge. A better understanding of the gender disparities in patients with ICH will hopefully lead to better outcomes in both sexes in the future.

Precipitating factors of hepatic encephalopathy in patients with chronic liver disease at Civil Hospital Karachi.

Patients with chronic liver disease (CLD) constitute a significant burden on the economy of the country. Approximately 3% of global population is estimated to be chronically infected with hepatitis C virus with an annual incidence of 3 to 4 million new cases globally. 1 Patients with CLD frequently experience episodes of exacerbations including hepatic encephalopathy precipitated by variety of established precipitants. 2 Hepatic encephalopathy is defined as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction, after exclusion of other known brain disease.2 It is characterized by personality changes, intellectual impairment, and a depressed level of consciousness. Identification of the precipitants and their prevention and/or immediate seeking of tertiary care facility may have significant impact on morbidity and mortality of patients presenting with hepatic encephalopathy. The objective of this study was to determine the frequency of factors likely to precipitate the hepatic encephalopathy in patients with CLD presenting to the Medical Wards of Civil Hospital, Karachi.

The safety of ethanol infusions for the treatment of methanol or ethylene glycol intoxication: an observational study

Methanol or ethylene glycol ingestion may result in significant morbidity or death without prompt treatment. Despite traditional and widespread use of intravenous ethanol as an antidote, its safety is not well described. An evaluation of the safety and ease of titrating ethanol infusions is necessary given the availability of an alternative antidote. To evaluate the safety and ease of titrating ethanol infusions for the treatment of methanol or ethylene glycol ingestion. We reviewed the hospital records of adults treated with ethanol at The Ottawa Hospital for methanol or ethylene glycol ingestion over a 9-year period. Using a standardized case report form, a single reviewer identified prespecified adverse events that developed after the start of ethanol therapy and classified dose adjustments during ethanol therapy as appropriate or inappropriate based on a priori criteria. Forty-nine cases of methanol or ethylene glycol ingestion treated with ethanol were included in the analysis, of which 45 underwent hemodialysis, 38 were admitted to the intensive care unit, and 4 died. At least one adverse event was identified in 45 (92%) cases, including 35 (71%) with agitation requiring chemical or physical restraints and 10 (20%) with a depressed level of consciousness treated with intubation. The median number of ethanol concentration measurements per treatment course was 6 (range 0-24), of which only 27% were within the target range of 22 to 30 mmol/L and 47% were below. When measured concentrations were outside the target, the adjustment in ethanol dosing (or lack thereof) was deemed inappropriate 59% of the time, including 69% of the time during hemodialysis. Based on actual practice in a large academic centre, adverse events occur frequently with intravenous ethanol infusions, and ethanol titration is inefficient. The safety profile and therapeutic drug monitoring considerations for ethanol should be considered when choosing an antidote for methanol or ethylene glycol ingestion.

Death due to extensive cervicomedullary infarction following iatrogenic vertebral artery occlusion

An 85 year old female with a medical history of hypertension and hyperlipidemia was newly diagnosed with carcinoma of the right breast with metastasis to the spine, resulting in a pathological fracture at the level of the second cervical vertebra. She underwent operative stabilization of the cervical spine. The operation was carried out under general anesthesia via the posterior approach. Occipital-cervical spine stabilization was established with the aid of an occipital plate, C1 lateral mass screws, C2 pars interarticularis screws, C3 lateral mass screws and C4 pedicle screws, with a connecting rod applied across the levels on each side. Immediately after the operation, the anesthetist observed the patient had prolonged apnea, depressed conscious level and a lack of gag reflex, despite cessation of all sedatives for more than an hour and the administration of intravenous naloxone. Her blood pressure started to drift downwards. She was conveyed to the intensive care unit for ventilatory and inotropic support. Postoperative MRI and MR angiogram revealed bilateral dorsolateral medullary infarcts extending to the upper cervical cord. The C2 pars interarticularis screws appeared to have been inserted/positioned close to the transverse foramina. The overall findings were suggestive of bilateral posterior spinal infarcts related to bilateral vertebral artery occlusions due to malpositioning of the surgical screws. Her condition gradually deteriorated and she died 5 days later.

Pulmonary Complications in Patients with Severe Brain Injury

Pulmonary complications are prevalent in the critically ill neurological population. Respiratory failure, pneumonia, acute lung injury and the acute respiratory distress syndrome (ALI/ARDS), pulmonary edema, pulmonary contusions and pneumo/hemothorax, and pulmonary embolism are frequently encountered in the setting of severe brain injury. Direct brain injury, depressed level of consciousness and inability to protect the airway, disruption of natural defense barriers, decreased mobility, and secondary neurological insults inherent to severe brain injury are the main cause of pulmonary complications in critically ill neurological patients. Prevention strategies and current and future therapies need to be implemented to avoid and treat the development of these life-threatening medical complications.

Behavioral and biochemical characterization of rats treated chronically with thioacetamide: proposal of an animal model for hepatic encephalopathy associated with cirrhosis

Hepatic encephalopathy (HE) is a syndrome observed in patients with liver dysfunction such as hepatitis and cirrhosis, and is characterized by cognitive impairment, personality changes, and a depressed level of consciousness. The detailed mechanism underlying the pathogenesis of HE remains unclear. In the present study, our aim was to establish an animal model for HE with cirrhosis. Therefore, we carried out behavioral and biochemical analysis of cirrhotic rats after treatment with thioacetamide (TAA) for 20 weeks. The rats subjected to chronic TAA treatment (TAA rats) showed reduction of cognitive scores in the novel object recognition test (NOR), and a decrease in immobility and an increase in swimming in the forced swim test (FST). In biochemical analyses, the TAA rats exhibited elevated blood levels of ammonia, and increased metabolic activities of serotonergic and noradrenergic neurons in the brain, while the levels of Glu and GABA were not affected. Post-oral treatment of lactulose, a clinically utilized drug for HE, effectively reduced the elevated blood ammonia levels, and restored the reduced cognitive scores and the decreased immobility, without any effects on neurotransmitter contents in the brain, compared with the control. These results indicated lactulose-restorable memory disturbance and irritated mood in the TAA rats. In other words, rats treated chronically with TAA are a potential model for cirrhosis-HE, and the combination of NOR and FST in TAA rats may be useful as a simple assay system for the screening and development of anti-HE agents.

Stroke Epidemiology, Patterns of Management, and Outcomes in Fortaleza, Brazil

Little information exists on the epidemiology and patterns of treatment of patients admitted to Brazilian hospitals with stroke. Our objective was to describe the frequency of risk factors, patterns of management, and outcome of patients admitted with stroke in Fortaleza, the fifth largest city in Brazil. Data were prospectively collected from consecutive patients admitted to 19 hospitals in Fortaleza with a diagnosis of stroke or transient ischemic attack from June 2009 to October 2010. We evaluated 2407 consecutive patients (mean age, 67.7±14.4 years; 51.8% females). Ischemic stroke was the most frequent subtype (72.9%) followed by intraparenchymal hemorrhage (15.2%), subarachnoid hemorrhage (6.0%), transient ischemic attack (3%), and undetermined stroke (2.9%). The median time from symptoms onset to hospital admission was 12.9 (3.8-32.5) hours. Hypertension was the most common risk factor. Only 1.1% of the patients with ischemic stroke received thrombolysis. The median time from hospital admission to neuroimaging was 3.4 (1.2-26.5) hours. In-hospital mortality was 20.9% and the frequency of modified Rankin Scale score≤2 at discharge was less than 30%. Older age, prestroke disability, and having a depressed level of consciousness at admission were independent predictors of poor outcome; conversely, male gender was a predictor of good outcome. The prevalence of stroke risk factors and clinical presentation in our cohort were similar to previous series. Treatment with thrombolysis and functional independency after a stroke admission were infrequent. We also found long delays in hospital admission and in evaluation with neuroimaging and high in-hospital mortality.