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

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

10 Years of Implementation of the "Glasgow 7" Quality Guarantee Program in the Mendoza Central Hospital: Epidemiology and Evolution of Neurocrytic Patients.

INTRODUCTION: In 2003, the Glasgow 7 Quality Guarantee Program was put into effect in Argentina with the objective of standardizing the donation and transplant process throughout the country, establishing the observation and registration of all neurocritical patients with a score on the Glasgow Coma Scale of 7 of 15 or less admitted to critical beds of selected establishments. MATERIALS AND METHODS: The following study is retrospective, observational, and cohort-based. It was developed in the Central Hospital of Mendoza, in the critical units, including guard, coronary, cardiovascular surgery recovery, and intensive care therapy. The inclusion criteria were admission to the institution with a score on the Glasgow Coma Scale of 7 or less with a structural cause of coma. Data collection was carried out in the national online database SINTRA. RESULTS: From January 1, 2008, to December 31, 2018, 1757 patients were enrolled at the Central Hospital of Mendoza, Argentina with Glasgow scores of 7 or less. The most frequent cause of coma was brain trauma (934 patients; 53%), followed by stroke (614 patients; 35%). Of those who scored 3 of 15 in the GCS upon admission, 65% progressed to brain death, whereas 72% of those who scored 7 were discharged. Of all these patients, 270 became donors, accounting for 43% of all brain deaths, whereas 187 had refused to become organ donors (30.6%). Of the total real donors, 55% were multiorganic (150 donors).

Early prediction of neurological outcome after barbiturate coma therapy in patients undergoing brain tumor surgery.

After a difficult brain tumor surgery, refractory intracranial hypertension (RICH) may occur due to residual tumor or post-operative complications such as hemorrhage, infarction, and aggravated brain edema. We investigated which predictors are associated with prognosis when using barbiturate coma therapy (BCT) as a second-tier therapy to control RICH after brain tumor surgery. The study included adult patients who underwent BCT after brain tumor surgery between January 2010 and December 2016. The primary outcome was neurological status upon hospital discharge, which was assessed using the Glasgow Outcome Scale (GOS). In the study period, 4,296 patients underwent brain tumor surgery in total. Of these patients, BCT was performed in 73 patients (1.7%). Among these 73 patients, 56 (76.7%) survived to discharge and 25 (34.2%) showed favorable neurological outcomes (GOS scores of 4 and 5). Invasive monitoring of intracranial pressure (ICP) was performed in 60 (82.2%) patients, and revealed that the maximal ICP within 6 h after BCT was significantly lower in patients with favorable neurological outcome as well as in survivors (p = 0.008 and p = 0.028, respectively). Uncontrolled RICH (ICP ≥ 22 mm Hg within 6 h of BCT) was an important predictor of mortality after BCT (adjusted hazard ratio 12.91, 95% confidence interval [CI] 2.788-59.749), and in particular, ICP ≥ 15 mm Hg within 6 h of BCT was associated with poor neurological outcome (adjusted odds ratio 9.36, 95% CI 1.664-52.614). Therefore, early-controlled ICP after BCT was associated with clinical prognosis. There were no significant differences in the complications associated with BCT between the two neurological outcome groups. No BCT-induced death was observed. The active and timely control of RICH may be beneficial for clinical outcomes in patients with RICH after brain tumor surgery.

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.

[Thyroid emergencies : Thyroid storm and myxedema coma]. / Schilddrüsennotfälle : Thyreotoxische Krise und Myxödemkoma.

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of a long-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (ß-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

[Severity assessment strategies based on administrative data using stroke as an example]. / Möglichkeiten zur Einschätzung des Schweregrades einer Erkrankung auf der Basis von Routinedaten am Beispiel des Schlaganfalls.

BACKGROUND AND OBJECTIVES: Information on disease severity is relevant for many studies with claims data in health service research, but only limited information is available in routine data. Stroke serves as an example to analyse whether the combination of different information in claims data can provide insight into the severity of a disease. METHOD: As a first step, a literature search was conducted. Strategies to assess the severity of a disease by means of routine data were examined with regard to approval and applicability to German sickness fund data. In order to apply and extend the identified procedures, the statutory health insurance sample AOK Hessen/KV Hessen (VSH) served as data source. It is an 18.75 % random sample of persons insured by the AOK Hessen, with 2013 being the most recent year. Stroke patients were identified by the ICD-10 GM code I63 and I64. Patients with said diagnoses being coded as a hospital discharge diagnosis in 2012 were included due to an acute event in 2012 (n=944). The follow-up time was one year. RESULTS: Ten studies covering seven different methods to assess stroke severity were identified. Codes for coma (4.2 % of stroke patients in the SHI sample) as well as coma and/or the application of a PEG tube (9.8 % of the stroke patients) were applied as a proxy for disease severity of acute cases. Taking age, sex and comorbidity into consideration, patients in a coma show a significantly increased risk of mortality compared to those without coma. Three operationalisations were chosen as possible proxies for disease severity of stroke in the further course of disease: i) sequelae (hemiplegia, neurological neglect), ii) duration of the index inpatient stay, and iii) nursing care/ care level 3 for the first time after stroke. The latter proxy has the highest explanatory value for SHI costs. CONCLUSION: The studies identified use many variables mainly based on hospital information in order to describe disease severity. With the exception of coma, these proxies were neither validated nor did the authors provide more detailed grounds for their use. An identified score for stroke severity could not be applied to SHI data. To develop a comparable score requires a linkage of clinical and administrative data. Since routine data include information from all sectors of care, it should be explored whether these data (for example, the patients' care needs) are suitable to assess disease severity. For validation, separate databases and, optimally, primary patient data are necessary.

Coma of unknown origin in the emergency department: implementation of an in-house management routine.

BACKGROUND: Coma of unknown origin is an emergency caused by a variety of possibly life-threatening pathologies. Although lethality is high, there are currently no generally accepted management guidelines. METHODS: We implemented a new interdisciplinary standard operating procedure (SOP) for patients presenting with non-traumatic coma of unknown origin. It includes a new in-house triage process, a new alert call, a new composition of the clinical response team and a new management algorithm (altogether termed "coma alarm"). It is triggered by two simple criteria to be checked with out-of-hospital emergency response teams before the patient arrives. A neurologist in collaboration with an internal specialist leads the in-hospital team. Collaboration with anaesthesiology, trauma surgery and neurosurgery is organised along structured pathways that include standardised laboratory tests and imaging. Patients were prospectively enrolled. We calculated response times as well as sensitivity and false positive rates, thus proportions of over- and undertriaged patients, as quality measures for the implementation in the SOP. RESULTS: During 24 months after implementation, we identified 325 eligible patients. Sensitivity was 60 % initially (months 1-4), then fluctuated between 84 and 94 % (months 5-24). Overtriage never exceeded 15 % and undertriage could be kept low at a maximum of 11 % after a learning period. We achieved a median door-to-CT time of 20 minutes. 85 % of patients needed subsequent ICU treatment, 40 % of which required specialised neuro-ICUs. DISCUSSION: Our results indicate that our new simple in-house triage criteria may be sufficient to identify eligible patients before arrival. We aimed at ensuring the fastest possible proceedings given high portions of underlying time-sensitive neurological and medical pathologies while using all available resources as purposefully as possible. CONCLUSIONS: Our SOP may provide an appropriate tool for efficient management of patients with non-traumatic coma. Our results justify the assignment of the initial diagnostic workup to neurologists and internal specialists in collaboration with anaesthesiologists.

The impact of lymphopenia on delirium in ICU patients.

BACKGROUND: Immunosuppressed states may predispose patients to development of acute brain injury during times of critical illness. Lymphopenia is a non-specific yet commonly used bedside marker of immunosuppressed states. METHODS: We examined whether lymphopenia would predict development of acute brain dysfunction (delirium and/or coma) in 518 patients enrolled in the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study in medical and surgical ICUs of a tertiary care, university-based medical center. Utilizing proportional odds logistic regression and Cox proportional hazards survival analysis, we assessed the relationship between pre-enrollment lymphocytes and subsequent cognitive outcomes including delirium- and coma-free days (DCFDs) and 30-day mortality. RESULTS: There were no statistically significant associations between lymphocytes and DCFDs (p = 0.17); additionally, the relationship between lymphocytes and mortality was not statistically significant (p = 0.71). Among 259 patients without history of cancer or diabetes, there was no statistically significant association between lymphocytes and DCFDs (p = 0.07). CONCLUSION: lymphopenia, a commonly used bedside marker of immunosuppression, does not appear to be a marker of risk for acute brain injury (delirium/coma) or 30-day mortality in general medical/surgical ICU patients.

Long-term outcomes after immediate aortic repair for acute type A aortic dissection complicated by coma.

OBJECTIVES: The management of acute type A aortic dissection complicated by coma remains controversial. We previously reported an excellent rate of recovery of consciousness provided aortic repair was performed within 5 hours of the onset of symptoms. This study evaluates the early and long-term outcomes using this approach. METHODS: Between August 2003 and July 2013, of the 241 patients with acute type A aortic dissection brought to the Japanese Red Cross Kobe Hospital and Hyogo Emergency Medical Center, 30 (12.4%) presented with coma; Glasgow Coma Scale was less than 11 on arrival. Surgery was performed in 186 patients, including 27 (14.5%) who were comatose. Twenty-four comatose patients underwent successful aortic repair immediately (immediate group). Their mean age was 71.0 ± 11.1 years, Glasgow Coma Scale was 6.5 ± 2.4, and prevalence of carotid dissection was 79%. For brain protection, deep hypothermia with antegrade cerebral perfusion was used, and postoperative induced hypothermia was performed. Neurologic evaluations were performed using the Glasgow Coma Scale, National Institutes of Health Stroke Scale, and modified Rankin Scale. RESULTS: In the immediate group, the time from the onset of symptoms to arrival in the operating theater was 222 ± 86 minutes. Hospital mortality was 12.5%. Full recovery of consciousness was achieved in 79% of patients in up to 30 days. Postoperative Glasgow Coma Scale and National Institutes of Health Stroke Scale improved significantly when compared with the preoperative score (P < .05), and postoperative activities of daily living independence (modified Rankin Scale <3) was achieved in 50% of patients. The mean follow-up period was 56.5 months, and the cumulative survival was 48.2% after 10 years. Cox proportional hazards regression analysis indicated that immediate repair (hazard ratio, 4.3; P = .007) was the only significant predictor of postoperative survival over a 5-year period. CONCLUSIONS: The early and long-term outcomes as a result of immediate aortic repair for acute type A aortic dissection complicated by coma were satisfactory.

Morbidity and mortality after massive transfusion in patients undergoing non-cardiac surgery.

BACKGROUND: Massive transfusion is associated with high morbidity and mortality, yet existing reports of massive transfusion are limited. Our primary aim was to determine the incidence of complications and 30-day mortality among patients who received massive transfusions and to explore risk factors associated with 30-day mortality. METHODS: We evaluated 971,455 patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. We assessed the associations between 30-day mortality and baseline, intraoperative, and postoperative factors among 5,143 patients who received massive transfusions and for whom complete data were available. RESULTS: The crude 30-day postoperative mortality of the non-transfused, low transfusion (1-4 units), and massive transfusion (≥ 5 units) patients in the NSQIP was 1.2%, 8.9%, and 21.5%, respectively. Of the 5,143 massive transfusion patients with non-missing covariable data, 17% (95% confidence interval [CI] 16% to 18%) died within 30 days of surgery, while 54% (95% CI 53% to 56%) had at least one non-fatal major complication. The following baseline and intraoperative variables were independently associated with 30-day mortality after adjusting for multiple testing: age, American Society of Anesthesiologists (ASA) physical status, emergency case, surgical types, coma > 24 hr before surgery, systemic sepsis, preoperative international normalized ratio of prothrombin time, the number of intraoperative transfusions, and requirement of postoperative transfusion. CONCLUSION: Massive transfusion is associated with substantial risk for respiratory and infectious complications and for mortality. Patients who died within 30 days of a massive perioperative transfusion were generally older, more likely to have vascular surgical procedure and abnormal international normalized ratio of prothrombin time, higher ASA physical status, preoperative coma and sepsis, and higher postoperative bleeding requiring transfusion, and they were likely given more intraoperative red cell units.

Medicine versus religion in the surgical intensive care unit: who is in charge?

The chief of surgery at a large academic medical center is approached by a vascular surgical faculty member. After a repair of an aortic dissection, an elderly man has remained comatose and has worsened over several weeks, developing multiple system organ failure. Statistically, his chance of leaving the hospital alive is <1%. The family is deeply religious, and the minister and various elders, deacons, and members of their church have been vigilant in constant prayerful attendance. The attending's tactful suggestions that the time is coming when nature should be allowed to take its course was not well received. The family and their support group are convinced that their fervor will summon a miracle. A large group complained to patient affairs and was taken to the medical center director's office. Today, the director told the attending that the hospital would absorb the overall cost until the patient dies and that the unfavorable press from stopping care is unacceptable. The chief of surgery should:

Patients with type A acute aortic dissection presenting with major brain injury: should we operate on them?

OBJECTIVES: The management strategy remains controversial for patients presenting with type A acute aortic dissection with cerebrovascular accident or coma. The present study aimed to help guide surgeons treating these high-risk patients. METHODS: Of 1873 patients with type A acute aortic dissection enrolled in the International Registry for Acute Dissection, 87 (4.7%) presented with cerebrovascular accident and 54 (2.9%) with coma. The hospital and 5-year results were stratified by the presence and type of brain injury (no injury vs stroke vs coma) and management type (medical vs surgical). Independent predictors of short- and mid-term survival were identified. RESULTS: Presentation with shock, hypotension, or tamponade (46.8% vs 25.2%; P < .001) and arch vessel involvement (55.0% vs 36.1%; P < .001) was more likely in patients with brain injury. Surgical management was avoided more often in patients with coma (33.3%) or cerebrovascular accident (24.1%) than in those without brain injury (11.1%; P < .001). The overall hospital mortality was 22.7% without brain injury, 40.2% with cerebrovascular accident, and 63.0% with coma (P < .001). Mortality varied among the management types for both cerebrovascular accident (76.2% medical vs 27.0% surgical; P < .001) and coma (100% medical vs 44.4% surgical; P < .001). Postoperatively, cerebrovascular accident and coma resolved in 84.3% and 78.8% of cases, respectively. On logistic regression analysis, surgery was protective against mortality in patients presenting with brain injury (odds ratio 0.058; P < .001). The 5-year survival of patients presenting with cerebrovascular accident and coma was 23.8% and 0% after medical management versus 67.1% and 57.1% after surgery (log rank, P < .001), respectively. CONCLUSIONS: Brain injury at presentation adversely affects hospital survival of patients with type A acute aortic dissection. In the present observational study, the patients selected to undergo surgery demonstrated improved late survival and frequent reversal of neurologic deficits.

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.

Incidence, predictors and outcomes of postoperative coma: an observational study of 858,606 patients.

CONTEXT: Coma is a state of profound unresponsiveness that can occur as a serious perioperative complication. The study of risk factors for, and sequelae of, postoperative coma has been limited due to the rarity of the event. OBJECTIVE: To determine the incidence, risk factors and impact of postoperative coma in a large patient population. DESIGN: Observational study using a prospectively gathered national dataset. PATIENTS: Data from 858 606 patients were analysed. MAIN OUTCOME MEASURES: The incidence of postoperative coma of more than 24-h duration was identified. Logistic regression was used to identify independent predictors and develop a risk model of postoperative coma in derivation and validation cohorts; 30-day mortality was also analysed. RESULTS: The incidence of postoperative coma was 0.06%. Multivariate analysis revealed the following independent predictors: liver disease, systemic sepsis, age at least 63 years, renal disease, emergency operation, cardiac disease, hypertension, prior neurological disease, diabetes mellitus and BMI 25 to 29.99 kg m (protective). These predictors were incorporated into a risk index classification; odds ratios for postoperative coma increased from 2.5 with one risk factor to 18.4 with three. Coma was associated with 74.2% all-cause mortality; coma associated with cardiac arrest had a 1.9-fold higher mortality. CONCLUSION: This is the largest study of postoperative coma ever reported and will be useful for determining risk of coma of more than 24 h duration when evaluating an unresponsive patient following surgery. Data on prognosis will aid medical and ethical decision-making for the comatose surgical patient.

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.

Prognosis in patients presenting with non-traumatic coma.

BACKGROUND: Studies of patients presenting with coma are limited, and little is known about the prognosis of these cases. OBJECTIVE: The aim of this study was to investigate the acute and long-term prognosis after an episode of non-traumatic coma. METHODS: Adults admitted consecutively to an emergency department in Stockholm, Sweden between February 2003 and May 2005 with a Glasgow Coma Scale (GCS) score of 10 or below were enrolled prospectively. All available data were used to explore the cause of the impaired consciousness on admission. Patients surviving hospitalization were followed-up for 2 years regarding survival. RESULTS: The final study population of 865 patients had the following eight different coma etiologies: poisoning (n = 329), stroke (n = 213), epilepsy (n = 113), circulatory failure (n = 60), infection (n = 56), metabolic disorder (n = 44), respiratory insufficiency (n = 33), and intracranial malignancy (n = 17). The hospital mortality rate among the 865 patients was 26.5%, varying from 0.9% for epilepsy to 71.7% for circulatory failure. The accumulated total 2-year mortality rate was 43.0%, varying from 13.7% for poisoning to 88.2% for malignancy. The level of consciousness on admission also influenced the prognosis: a GCS score of 3-6 was associated with a significantly higher hospital mortality rate than a GCS score of 7-10. CONCLUSION: The prognosis in patients presenting with non-traumatic coma is serious and depends largely on both the level of consciousness on admission and the etiology of the coma. Adding the suspected coma etiology to the routine coma grading of these emergencies may more accurately predict their prognosis.

Short-term and long-term mortality following pediatric intensive care.

BACKGROUND: The aim of the present study was to examine short-term and long-term mortality following discharge from the pediatric intensive care unit (PICU). METHODS: This was a prospective observational study. Data collected consisted of demographics, severity scores, procedures, treatment, need for and duration of mechanical ventilation (MV), length of PICU and hospital stay, and mortality at PICU and hospital discharge, at 3 and 6 months and at 1 and 2 years. RESULTS: A total of 300 patients (196 boys and 104 girls), aged 54.26 ± 49.93 months, were included in the study. Median (interquartile range) Pediatric Risk of Mortality (PRISM III-24) score was 7 (3-11) and predicted mortality rate was 11.16%. MV rate was 67.3% (58.3% at admission) for 6.54 ± 14.15 days, and length of PICU and hospital stay was 8.85 ± 23.28 days and 20.69 ± 28.64 days, respectively. Mortality rate at discharge was 9.7% and cumulative mortality rate thereafter was 12.7%, 15.0%, 16.7%, 19.0%, and 19.0% at hospital discharge, 3 months, 6 months, 1 year and 2 years, respectively. Significant risk factors of PICU mortality were inotrope use, PRISM III-24 score >8, MV, arterial and central venous catheterization, nosocomial infection, complications, and cancer. Independent predictors of mortality at discharge were inotrope use and PRISM III-24 score, whereas predictors of mortality at 2 years were comorbidity and cancer. CONCLUSIONS: A 2 year follow-up period seems sufficient for a comprehensive mortality analysis of PICU patients. Severity of critical illness is the key factor of short-term mortality, whereas comorbidity is the major determinant of long-term mortality.

Comparing acute toxicity of first- and second-generation antipsychotic drugs: a 10-year, retrospective cohort study.

OBJECTIVE: Second-generation antipsychotics (SGAs) are far more commonly used in the United States compared to first-generation antipsychotics (FGAs), but the relative safety of SGAs compared to FGAs following acute toxic ingestions has not been studied. METHOD: A retrospective cohort study was performed by chart review of the California Poison Control System electronic database of 1975 cases from the 10-year period 1997 to 2006 involving patients aged 18 to 65 years who ingested a single SGA or FGA. Cases were coded for overall severity of adverse outcome as defined by the American Association of Poison Control Centers criteria and for presence of specific symptoms and treatments. Odds ratios were calculated between SGAs and FGAs for various symptoms, treatments, and outcome severity. RESULTS: Odds of a major adverse outcome or death were significantly higher for SGAs than FGAs (OR = 1.71, 95% CI = 1.09 to 2.71). Patients taking SGAs had higher odds of respiratory depression (OR = 2.39, 95% CI = 1.09 to 5.26), coma (OR = 2.18, 95% CI = 1.30 to 3.65), and hypotension (OR = 1.80, 95% CI = 1.23 to 2.63) compared to those taking FGAs but lower odds of dystonia (OR = 0.12, 95% CI = 0.08 to 0.19) or rigidity (OR = 0.30, 95% CI = 0.10 to 0.90). CONCLUSION: SGAs appear no safer than FGAs in acute overdose. While neuromuscular symptoms appear less frequently with SGAs compared to FGAs, the relatively greater rates of central nervous system depression associated with SGA overdose may be more dangerous.