Corrigendum to "Benzodiazepine use for perioperative insomnia and increased risk of post-traumatic stress disorder symptoms after cardiac surgery: A large retrospective cohort study" [General Hospital Psychiatry 100 (2026) 148-155

Benzodiazepine use for perioperative insomnia and increased risk of post-traumatic stress disorder symptoms after cardiac surgery: A large retrospective cohort study.

Cohort Studies: Design and Pitfalls

Intraoperative Transesophageal Echocardiography During Coronary Artery Bypass Graft Surgery (CABG): A Major Step Toward Improving Outcomes in Cardiac Surgery

In this article we assessed the prevalence of benzodiazepine (BZD) use in women before and during imprisonment, as well as its related factors and association with symptoms of anxiety, depression, and posttraumatic stress disorder in a quantitative, cross-sectional, analytical study of regional scope. Two female prisons in the Brazilian Prison System were included. Seventy-four women participated by completing questionnaires about their sociodemographic data, BZD use and use of other substances. These questionnaires included the Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Posttraumatic Stress Disorder Checklist–Civilian Version (PCL-C). Of the 46 women who reported no BZDs use before arrest, 29 (63%) began using BZDs during imprisonment (p < 0.001). Positive scores for PTSD, anxiety, and depression, as well as associations between BZD use during imprisonment and anxiety (p = 0.028), depression (p = 0.001) and comorbid anxiety and depression (p = 0.003) were found when a bivariate Poisson regression was performed. When a multivariate Poisson regression was performed for tobacco use, the PHQ-9 and GAD-7 scales, BZD use was associated with depression (p = p = 0.008), with tobacco use (p = 0.012), but not with anxiety (p = 0.325). Imprisonment increases the psychological suffering of women, consequently increasing BZD use. Nonpharmacological measures need to be considered in the health care of incarcerated women.

Aims: Risk and demographic factors for benzodiazepine and z-hypnotic use are incompletely understood. The aim of the paper was therefore to investigate socio-demographic, lifestyle and psychological factors predicting onset and differential pattern of prescribed benzodiazepine and z-hypnotic use in a Norwegian population sample. Methods: This retrospective cohort study obtained socio-demographic, psychological and lifestyle variables from the Nord-Trøndelag Health Study. Information about benzodiazepine prescriptions from the Norwegian prescription database were linked to epidemiological questionnaire data. Benzodiazepine use was classified into single-period, intermittent and chronic use, and high dose use was defined as being prescribed a yearly average above 180 daily defined doses. Results: Older age, sleep difficulties and smoking were positively associated with all patterns of benzodiazepine use. Male gender was related to a reduced risk of all patterns of use, whereas educational achievement was negatively associated with single-period use. Alcohol consumption, anxiety and tension were positively related to intermittent and chronic use, while exercise was negatively related to chronic use. Smoking, sleep difficulties and old age were positively associated with prescriptions of high benzodiazepine doses, while exercise was associated with lower doses. Conclusions: Patterns of prescribed benzodiazepine use are linked to demographic, lifestyle and clinical variables. Non-pharmacological treatment for sleep difficulties and smoking cessation may reduce the risk of chronic benzodiazepine use.

Growing Pains: Opportunity Knocks in the 2022 Center for Disease Control Clinical Practice Guidelines for Prescribing Opioids for Pain

The aim of this study was to describe the epidemiology of new and new persistent benzodiazepine (BZD) use following admissions to internal medicine and its relationship with patient and admission characteristics. Retrospective study that including all admissions of patients 18 years and older to Landspítali - The National University Hospital of Reykjavík, Iceland, between 2010 and 2020. BZD-naïve patients in the year preceding admission were classified into patients with new BZD use (filling one or more BZD prescriptions within 90 days of discharge), and new persistent use (filling a second prescription between 90 and 180 days). Among 54,844 eligible admissions, 6.3% (3471/54,844) initiated new use, and of those 39.4% (95% CI 37.8-41.0) developed new persistent use. Female sex and admission to several specialties, including cardiology, gastroenterology, pulmonology, neurology, rheumatology, hematology, oncology, or palliative care were associated with an increased risk of initiating new BZD use compared with general medicine (reference group). Medium and high frailty risk was associated with reduced odds of new use. Among patients who initiated new use, the risk of initiating new persistent BZD use was higher in female patients and patients with underlying COPD as well as patients admitted to cardiology, gastroenterology, pulmonology, geriatrics, hematology, or oncology services. The incidence of new BZD use following admissions to internal medicine in Iceland is high and a large portion of patients who initiate new use transition to new persistent use. This highlights the need for strategies to reduce the likelihood of new BZD use and reduce the risk of unintended transition of new persistent BZD use to ensure appropriate short-term BZD use. Further research is needed to understand the drivers of specialty-level variation in post-discharge BZD dispensing.

Objective: This study aimed to describe the pattern of benzodiazepine use in a representative sample of patients with schizophrenia in Taiwan. Methods: Data from the National Health Insurance Research Database in Taiwan were used to examine the prevalence and indices of benzodiazepine use in 2005. Demographic and clinical characteristics associated with long-term benzodiazepine use (more than 180 days of cumulated prescription in one year) were further explored by multivariate logistic regression analysis. Results: Among the 3,690 patients with schizophrenia, the one-year prevalence rate of benzodiazepine use was 79.2% (N=2,923). Among those who used benzodiazepines, 1,840 (62.9%) were long-term users. Use of benzodiazepines was associated with having a comorbid psychiatric disorder, use of concomitant psychotropic agents, and antipsychotic polypharmacy. Among benzodiazepine users, older age, longer duration of illness, and use of concomitant psychotropic agents were associated with significantly higher odds of being a long-term user. Conclusions: The study showed that benzodiazepine use was highly prevalent among patients with schizophrenia in Taiwan and that a substantial proportion of users (62.9%) were long-term users. Because long-term use was associated with longer duration of illness and with use of concomitant psychotropic medications, long-term users may be at higher risk of neurocognitive side effects caused by benzodiazepines and interactions with other psychotropic medications. Therefore, this group should be closely monitored for drug-drug interactions and the benefits and risks of benzodiazepine use. (Psychiatric Services 62:908–914, 2011)

One-third of opioid (OPI) overdose deaths involve concurrent benzodiazepine (BZD) use. Little is known about concurrent opioid and benzodiazepine use (OPI-BZD) most associated with overdose risk. We aimed to examine associations between OPI-BZD dose and duration trajectories, and subsequent OPI or BZD overdose in US Medicare. Retrospective cohort study. US Medicare. Using a 5% national Medicare data sample (2013-16) of fee-for-service beneficiaries without cancer initiating OPI prescriptions, we identified 37 879 beneficiaries (age ≥ 65 = 59.3%, female = 71.9%, white = 87.6%, having OPI overdose = 0.3%). During the 6 months following OPI initiation (i.e. trajectory period), we identified OPI-BZD dose and duration patterns using group-based multi-trajectory models, based on average daily morphine milligram equivalents (MME) for OPIs and diazepam milligram equivalents (DME) for BZDs. To label dose levels in each trajectory, we defined OPI use as very low (< 25 MME), low (25-50 MME), moderate (51-90 MME), high (91-150 MME) and very high (>150 MME) dose. Similarly, we defined BZD use as very low (< 10 DME), low (10-20 DME), moderate (21-40 DME), high (41-60 DME) and very high (> 60 DME) dose. Our primary analysis was to estimate the risk of time to first hospital or emergency department visit for OPI overdose within 6 months following the trajectory period using inverse probability of treatment-weighted Cox proportional hazards models. We identified nine distinct OPI-BZD trajectories: group A: very low OPI (early discontinuation)-very low declining BZD (n = 10 598; 28.0% of the cohort); B: very low OPI (early discontinuation)-very low stable BZD (n = 4923; 13.0%); C: very low OPI (early discontinuation)-medium BZD (n = 4997; 13.2%); D: low OPI-low BZD (n = 5083; 13.4%); E: low OPI-high BZD (n = 3906; 10.3%); F: medium OPI-low BZD (n = 3948; 10.4%); G: very high OPI-high BZD (n = 1371; 3.6%); H: very high OPI-very high BZD (n = 957; 2.5%); and I: very high OPI-low BZD (n = 2096; 5.5%). Compared with group A, five trajectories (32.3% of the study cohort) were associated with increased 6-month OPI overdose risks: E: low OPI-high BZD [hazard ratio (HR) = 3.27, 95% confidence interval (CI) = 1.61-6.63]; F: medium OPI-low BZD (HR = 4.04, 95% CI = 2.06-7.95); G: very high OPI-high BZD (HR = 6.98, 95% CI = 3.11-15.64); H: very high OPI-very high BZD (HR = 4.41, 95% CI = 1.51-12.85); and I: very high OPI-low BZD (HR = 6.50, 95% CI = 3.15-13.42). Patterns of concurrent opioid and benzodiazepine use most associated with overdose risk among fee-for-service US Medicare beneficiaries initiating opioid prescriptions include very high-dose opioid use (MME > 150), high-dose benzodiazepine use (DME > 40) or medium-dose opioid with low-dose benzodiazepine use.

A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission. PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO. Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction. Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist. Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high methodological quality generally found benzodiazepine use to be a risk factor for the development of delirium. Five studies reported an association between benzodiazepine use and symptoms of posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction after ICU admission; five studies reported mixed findings, and in four studies, no association was found. No association was found with methodological quality and sample size for these findings. Meta-analysis was not feasible due to major differences in study methods. The majority of included studies indicated that benzodiazepine use in the ICU is associated with delirium, symptoms of posttraumatic stress disorder, anxiety, depression, and cognitive dysfunction. Future well-designed studies and randomized controlled trials are necessary to rule out confounding by indication.

Coffee Consumption and Risk of Liver Cancer: A Meta-Analysis

2010 Standard of Care for Central Nervous System Monitoring During Cardiac Surgery

Mental health disorders can occur in patients with pain conditions, and there have been reports of an increased risk of persistent pain after THA and TKA among patients who have psychological distress. Persistent pain may result in the prolonged consumption of opioids and other analgesics, which may expose patients to adverse drug events and narcotic habituation or addiction. However, the degree to which preoperative use of antidepressants or benzodiazepines is associated with prolonged analgesic use after surgery is not well quantified. (1) Is the preoperative use of antidepressants or benzodiazepine medications associated with a greater postoperative use of opioids, NSAIDs, or acetaminophen? (2) Is the proportion of patients still using opioid analgesics 1 year after arthroplasty higher among patients who were taking antidepressants or benzodiazepine medications before surgery, after controlling for relevant confounding variables? (3) Does analgesic drug use decrease after surgery in patients with a history of antidepressant or benzodiazepine use? (4) Does the proportion of patients using antidepressants or benzodiazepines change after joint arthroplasty compared with before? Of the 10,138 patients who underwent hip arthroplasty and the 9930 patients who underwent knee arthroplasty at Coxa Hospital for Joint Replacement, Tampere, Finland, between 2002 and 2013, those who had primary joint arthroplasty for primary osteoarthritis (64% [6502 of 10,138] of patients with hip surgery and 82% [8099 of 9930] who had knee surgery) were considered potentially eligible. After exclusion of another 8% (845 of 10,138) and 13% (1308 of 9930) of patients because they had revision or another joint arthroplasty within 2 years of the index surgery, 56% (5657 of 10,138) of patients with hip arthroplasty and 68% (6791 of 9930) of patients with knee arthroplasty were included in this retrospective registry study. Patients who filled prescriptions for antidepressants or benzodiazepines were identified from a nationwide drug prescription register, and information on the filled prescriptions for opioids (mild and strong), NSAIDs, and acetaminophen were extracted from the same database. For the analyses, subgroups were created according to the status of benzodiazepine and antidepressant use during the 6 months before surgery. First, the proportions of patients who used opioids and any analgesics (that is, opioids, NSAIDs, or acetaminophen) were calculated. Then, multivariable logistic regression adjusted with age, gender, joint, Charlson Comorbidity Index, BMI, laterality (unilateral/same-day bilateral), and preoperative analgesic use was performed to calculate odds ratios for any analgesic use and opioid use 1 year postoperatively. Additionally, the proportion of patients who used antidepressants and benzodiazepines was calculated for 2 years before and 2 years after surgery. At 1 year postoperatively, patients with a history of antidepressant or benzodiazepine use were more likely to fill prescriptions for any analgesics than were patients without a history of antidepressant or benzodiazepine use (adjusted odds ratios 1.9 [95% confidence interval 1.6 to 2.2]; p < 0.001 and 1.8 [95% CI 1.6 to 2.0]; p < 0.001, respectively). Similarly, patients with a history of antidepressant or benzodiazepine use were more likely to fill prescriptions for opioids than patients without a history of antidepressant or benzodiazepine use (adjusted ORs 2.1 [95% CI 1.7 to 2.7]; p < 0.001 and 2.0 [95% CI 1.6 to 2.4]; p < 0.001, respectively). Nevertheless, the proportion of patients who filled any analgesic prescription was smaller 1 year after surgery than preoperatively in patients with a history of antidepressant (42% [439 of 1038] versus 55% [568 of 1038]; p < 0.001) and/or benzodiazepine use (40% [801 of 2008] versus 55% [1098 of 2008]; p < 0.001). The proportion of patients who used antidepressants and/or benzodiazepines was essentially stable during the observation period. Surgeons should be aware of the increased risk of prolonged opioid and other analgesic use after surgery among patients who were on preoperative antidepressant and/or benzodiazepine therapy, and they should have candid discussions with patients referred for elective joint arthroplasty about this possibility. Further studies are needed to identify the most effective methods to reduce prolonged postoperative opioid use among these patients. Level III, therapeutic study.

Benzodiazepines are excluded from prescription drug coverage under Medicare Part D. The objectives of this study were twofold: to provide national estimates of benzodiazepine utilization and expenditure patterns and to examine the impact of drug coverage and other factors associated with utilization of benzodiazepines and potential benzodiazepine substitute classes. The 2002 Medicare Current Beneficiary Survey provided national estimates of benzodiazepine use and expenditures among Medicare beneficiaries. Multivariate logistic regression was conducted to assess the relationships between independent variables and use of benzodiazepines and potential substitute classes. The independent variable of interest was drug coverage, assessed by payer source. Other covariates included in the models were chronic conditions associated with benzodiazepine use, age, sex, race, and income. In 2002, 13.7% of Medicare beneficiaries received at least one benzodiazepine fill, with an average of 5.8 benzodiazepine prescriptions filled at an annual cost of 190 dollars. Specific sources of prescription drug coverage were not significantly associated with benzodiazepine use. Female gender, chronic mental illness, age under 65, and lower income were significantly positively associated with benzodiazepine use in the Medicare population, whereas black and other races were significantly negatively associated with benzodiazepine use in this population. Compared with Medicare beneficiaries without supplemental drug coverage, beneficiaries with supplemental drug coverage were more likely to use potential benzodiazepine substitute classes than benzodiazepines. Benzodiazepines were widely used by Medicare beneficiaries. Drug coverage influences access to benzodiazepines and potential substitute classes. These findings have important implications for identifying beneficiaries potentially affected by the exclusion of benzodiazepine coverage under Medicare Part D.

J. Lance Lichtor, M.D., and Joseph F. Antognini, M.D., Editors Joint arthroplasty is becoming a more common procedure and is currently offered to older patients, who are at greater risk of stroke. Therefore, although the rate of stroke after general surgery is low (0.2%), the overall risk of stroke after joint arthroplasty is increasing and may result in increased mortality.Using a case-controlled retrospective study from a prospective database, this study analyzed the incidence of perioperative stroke at a single institution among patients undergoing total joint arthroplasty during an 8-yr study period. Discharge abstracts and daily complication forms were used to identify patients diagnosed with cerebrovascular accident or stroke. Patients who had a stroke after hospital discharge were also included through evaluation of electronic medical records.Of 18,745 patients who underwent primary or revision total knee or total hip arthroplasty, 36 patients (0.2%) had a stroke during hospital stay or within 30 days of surgery. The mean age of patients having a stroke was 68.2 yr. The majority (94%) were ischemic and two were hemorrhagic. The rate of mortality at 1 yr was 25%, with four patients dying during hospital stay. A history of coronary artery disease, cerebrovascular disease, atherosclerotic disease, or noncoronary cardiac disease were significantly associated with stroke. Independent predictors of stroke included history of noncoronary cardiac disease (odds ratio = 4.13), urgent versus elective surgery (odds ratio = 5.89), general anesthesia (odds ratio = 3.54), and intraoperative arrhythmia or changes in mean heart rate during surgery (odds ratio = 1.06). Stroke occurred most often on postoperative day 1.In an analysis of perioperative stroke at a single institution for patients undergoing total joint arthroplasty, the authors found the incidence to be 0.2–0.4% in patients aged 75 yr or older. As expected, patients who suffered a stroke had a greater incidence of in-hospital mortality, discharge to a medical or chronic care facility versus home, and a longer hospital length of stay.Perioperative respiratory adverse events are a major cause of morbidity and mortality in pediatric patients receiving anesthesia. With increasing rates of pediatric asthma and a rising incidence of upper respiratory tract infections, the rates and risk of perioperative respiratory adverse events have also increased. To help reduce the rate of this complication, introduction of an appropriate risk-assessment questionnaire would be helpful.Using a large cohort (N = 9,297) prospective study of children undergoing general anesthesia for surgical or medical interventions at a single institution, family medical history and perioperative respiratory adverse event data were collected. A modified form of the International Study of Asthma and Allergies in Childhood questionnaire was used by anesthetists on the day of surgery. Information about passive or active smoking was also included.Mean patient age was 6.21 yr, 60% were boys, and most (65%) were undergoing elective procedures. Baseline respiratory factors were low in the majority of patients: 66% had never had an upper respiratory tract infection, 85% had not had a wheezing attack within 12 months, 69% did not have a family history of asthma, and 76% did not have a family history of rhinitis. Overall, 15% of patients had perioperative respiratory adverse events, including oxygen desaturation (10%), coughing (7%), laryngospasm (4%), airway obstruction (4%), bronchospasm (2%), and stridor (1%). The rate of adverse events was higher among patients who had urgent versus elective procedures (17 vs. 14%; P = 0.001).In a large, prospective study of children who underwent general anesthesia, increased occurrence of perioperative respiratory symptoms and events were found among those with the following characteristics: eczema, family history of asthma, upper respiratory infection within 2 weeks of the procedure, rhinitis, exposure to tobacco smoke, and induction with propofol rather than sevoflurane. Laryngospasm frequency decreased with increasing age. An accompanying editorial notes that this large study adds significantly to our understanding of perioperative respiratory adverse events in a cross-section of children undergoing surgery.Maintenance of glucose concentrations is a highly regulated process that may be altered or impaired as a result of traumatic injury. Hyperglycemia has been associated with increased intensive care and hospital length of stay, infection, and mortality.To evaluate a computational and graded algorithmic model to predict infection and outcomes among critically injured trauma patients, a large, prospective study was conducted with intensive care unit patients. After glucose stabilization (48 h with no significant change), daily monitoring for acute glucose elevation was conducted.The majority of patients were men (77%) admitted for blunt injury (85%). Of the 2,200 patients observed, only 1,236 achieved glucose normalization and stabilization and were included in the study. Twenty-six percent of patients experienced infections within the first 2 weeks of hospitalization. When stratified by acute glucose elevation classification class I-IV, the most common infections were bloodstream and catheter-related (33%), respiratory (28%), intraabdominal (16%), or genitourinary (16%). The algorithm demonstrated specificity and sensitivity with positive predictive value for infection in the acute glucose elevation class IV group. Mortality was highest in the class III and IV groups (P &lt; 0.001). The number of ventilator days, intensive care unit length of stay, and hospital length of stay were also significantly greater among patients with class III and IV acute glucose elevation (P &lt; 0.001).Hyperglycemia can have adverse effects on trauma patients during the postoperative period. These data show that hyperglycemia was associated with increased incidence of infection, need for ventilation, and mortality in trauma patients. Therefore, glucose elevation should be monitored to help predict and improve patient outcomes.The second most common cause of death as a result of blunt trauma is blunt thoracic aortic injury. The mortality rate for these patients using standard-of-care open repair of blunt thoracic aortic injury is 5–28%. Endovascular stent grafts may provide a faster way to treat injury and improve mortality.In a retrospective analysis of 24 consecutive patients, the efficacy of thoracic endovascular aortic repair was assessed during a 7-yr study period. Imaging (chest roentgenogram and computed tomography scan) was used to identify the extent of injury and measure proximal and distal neck length and aortic diameter. Patients underwent follow-up imaging studies at 1, 7, 12, and 24 months, and then every 2–3 yr after aortic repair.Of 24 patients, 71% were men with a mean age of 41 yr. The majority of these patients had been injured in motor vehicle crashes. Mean injury severity score was 43. In 75% of patients, thoracic endovascular aortic repair was performed within 24 h of injury. Based on angiography and computed tomography results at the time of intervention, thoracic endovascular aortic repair was successful in all patients. One patient died of multisystem organ failure as a result of other associated injuries. Overall 30-day mortality was 4%. Access site complications occurred in two patients (8%) and one patient required a second intervention because of a collapsed device. One death was reported from unrelated causes after a mean follow-up time of 21 months. To date, there have been no additional device failures or complications.Thoracic aorta injury after blunt trauma carries high rates of mortality. Open repair is the usual manner in which these injuries are treated. However, this small study showed that endovascular repair is a potential alternative that is effective and does not increase complications. Future larger, prospective trials are warranted.At least 30% of patients with severe symptomatic aortic stenosis do not undergo surgery because of high surgical risk. However, among untreated patients, the rate of death is 50% within the first 2 yr of symptoms. Transcatheter aortic-valve implantation (TAVI) is a new procedure that may benefit patients at high surgical risk.The PARTNER (Placement of AoRTic TraNscathetER Valves) Trial is a multicenter study that compared TAVI with standard therapy in patients with severe aortic stenosis. Trial investigators noted patients who were not suitable candidates for surgery. Patients had an aortic-valve area of less than 0.8 cm2, a mean aortic valve gradient of at least 40 mmHg, a peak aortic jet velocity of at least 4.0 m/s, and class II-IV symptoms on the New York Heart Association functional classification system. Patients deemed to be not good candidates for surgery were randomly assigned to TAVI or standard therapy.Overall, 358 patients at 21 sites were randomly assigned to TAVI (n = 179) or standard therapy (n = 179). Thirty-day mortality rates were 5.0% and 2.8% (P = 0.41) whereas 1-yr mortality was 30.7% and 50.7% (P &lt; 0.001), respectively. The rate of death as a result of cardiovascular causes was also lower at 1 yr in the TAVI group (20.5 vs. 44.6%; P &lt; 0.001). However, more patients in the TAVI group experienced major strokes (5.0 vs. 1.1%; P = 0.06) at both 30-day and 1-yr follow-up. Similarly, the frequency of major vascular complications and bleeding were also higher in the TAVI group.Aortic stenosis is one of the most serious valvular diseases, but operative repair can be dangerous in critically ill patients. In this study, transcatheter aortic valve implantation was used to treat severe aortic stenosis in patients with coexisting disease. Although TAVI patients had lower mortality and better cardiac function than standard-care patients, their incidence of stroke was higher.Jean Mantz, M.D., Ph.D., Editor Critically ill patients with traumatic brain injury are at higher risk for pulmonary complications and poor outcomes. Despite the high frequency of these events, relatively little is known regarding the relationship between brain tissue oxygen tension (PbtO2) and lung function. A large cohort study was conducted to analyze the association between brain tissue and systemic oxygenation.A retrospective study of a prospective observational database of patients with traumatic brain injury admitted to a level I trauma center was conducted. All patients were intubated and mechanically ventilated and were monitored for PbtO2and intracranial pressure.Of 78 patients, the majority (78%) were men. Median Acute Physiology and Chronic Health Evaluation II score was 20, and 55% had a favorable outcome at 30 days. PbtO2was less than 20 mmHg in 23% of patients with an unfavorable outcome, compared with only 8% of patients with a favorable outcome (P &lt; 0.001). Lower PaO2/FIO2ratios were also significantly associated with reduced PbtO2values. Overall, there was a linear correlation among PbtO2and PaO2/FIO2(P &lt; 0.01), PaO2(P &lt; 0.01), and SaO2(P &lt; 0.03). Acute lung injury was observed in 60% of patients, and of these 85% had compromised PbtO2values compared with 54% of patients without acute lung injury. A PaO2/FIO2ratio lower than 300 was an independent risk factor for compromised PbtO2in patients with traumatic brain injury (odds ratio = 2.13).This retrospective observational study suggests that PbtO2strongly correlates with systemic oxygenation in patients with severe, nonpenetrating brain injury. Patients with severe brain injury who also had acute lung injury had decreased brain tissue oxygenation. These results support the use of lung-protective strategies aimed at improving oxygenation to limit secondary hypoxic insults to the brain.Constipation is a common gastrointestinal complication of mechanical ventilation. Despite the known associations of constipation with prolonged intensive care unit (ICU) length of stay and increased mortality, constipation has not been widely studied in patients.Using a prospective observational design, this study aimed to characterize the causes of constipation in patients in the ICU receiving mechanical ventilation for more than 6 days. Patients admitted to the ICU during the 41-month study period were observed for stool passage. Management of constipation was not protocolized.Of 609 patients admitted to the ICU and included in the study, approximately half (42%) had “early” (less than 6 days) passage of stools and 58% had “late” (6 days or more) passage of stools. Baseline characteristics and time to enteral feeding were not significantly different between these two study groups. Length of ICU stay (15 vs. 17 days), duration of mechanical ventilation (11 vs. 14 days), central venous catheter use (10 vs. 12 days), and mortality rates (47 vs. 107%) were significantly different in the early versus late passage of stool groups. Overall, the median time until the first passage of stools was 6 days. A PaO2/FIO2ratio lower than 150 mmHg (hazard ratio = 1.40) and systolic blood pressure of 70–89 mmHg (hazard ratio = 1.48) or less than 69 mmHg (hazard ratio = 1.29) were associated with delayed defecation.This paper highlights a frequent and potentially harmful adverse event in ICU patients, constipation. Whether constipation is a surrogate marker of severity of illness or a predictor of poor outcome cannot be established from this study. However, an association between constipation lasting more than 6 days and worsened ICU outcome, including mortality, is suggested.Surgical patients receiving large volumes of infusions for fluid management are at risk for serum sodium imbalances. Although often studied in medical intensive care units (ICU), hypernatremia in surgical ICU patients has not been studied as widely.To identify the incidence of hypernatremia (serum sodium concentration higher than 145 mM) after major cardiac surgery and to determine whether its development is associated with adverse outcomes, a retrospective analysis of a prospectively collected database was performed. During the 8-yr study period, data were collected from 2,314 patients scheduled for any of the following procedures: cardiac surgery with cardiopulmonary bypass, coronary artery bypass grafting with or without cardiopulmonary bypass, thoracic aortic surgery with cardiopulmonary bypass, heart or lung transplant surgery, scheduled insertion of a cardiac assist device, operation on the descending aorta, or thromboendarterectomy of the pulmonary arteries. Only patients without hypernatremia or hyponatremia at ICU admission were included.The average age of ICU patients was 62 yr, most (64%) were male, and had undergone either coronary artery (30%) or valve (26%) surgery. Ten percent of patients acquired hypernatremia during ICU stay, with the first incident occurring on day 4 of ICU stay. Patients who died in the ICU (n = 200) had higher Simplified Acute Physiology Score II and euroSCORE totals, lower body mass indexes, longer surgery duration, higher preoperative sodium concentrations and ICU-acquired hypernatremia, and higher postoperative lactate concentration.In this retrospective, large cohort study, hypernatremia was present in 10% of patients and was identified as a predictor of mortality at 28 days. Although this study has limitations, it suggests that treatments aimed at maintaining serum sodium concentrations below 145 mM should be considered in surgical ICU patients.Acute respiratory distress syndrome occurs in critically ill patients and may be fatal in as many as 60% of patients. Although current guidelines recommend the use of neuromuscular blocking agents in mechanically ventilated patients, further investigation of outcomes (including mortality) are needed.A multicenter, randomized, placebo-controlled, double-blind trial was conducted to assess the effects of a shorter period of treatment with cisatracurium besylate (a neuromuscular blocking agent) early in the course of severe acute respiratory distress syndrome. At 20 intensive care units in France, patients with endotracheal mechanical ventilation for acute hypoxemic respiratory failure received an intravenous infusion of either cisatracurium besylate (15 mg bolus, then 37.5 mg continuous infusion for 48 h) or placebo.Compared with the placebo group—and after adjustments for PaO2/FIO2ratio, Simplified Acute Physiology Score II, and plateau pressure—the hazard ratio for death at 90 days was 0.68 in the cisatracurium group (P = 0.04). In patients with PaO2/FIO2ratios lower than 120, 90-day mortality was lower in the cisatracurium versus placebo group (30.8 vs. 44.6%; P = 0.04). Likewise, 28-day mortality was lower in the cisatracurium versus placebo group (23.7 vs. 33.3%; P = 0.05) as were the number of ventilator-free days (53.1 vs. 44.6 days; P = 0.03).In this prospective, randomized, double-blind, multicenter, placebo-controlled trial, early administration of cisatracurium for 48 h after severe acute respiratory distress syndrome improved survival at 90 days and decreased ventilator time without increasing muscular weakness. This study should encourage the use of muscle relaxants in intensive care unit patients at the early stage of severe acute respiratory distress syndrome.Timothy J. Brennan, Ph.D., M.D., Editor There is a need for improved therapies with a better side-effect profiles for patients with osteoarthritis of the knee. Tanezumab, a humanized immunoglobulin G2 monoclonal antibody directed against nerve growth factor (NGF), has shown potential in phase I clinical trials.This randomized, placebo-controlled, proof-of-concept study assessed the safety, side-effect profile, and efficacy of repeated doses of tanezumab in patients with advanced osteoarthritis of the knee. Adult patients with radiographically confirmed osteoarthritis were randomized to receive placebo or tanezumab (10, 25, 50, 100, or 200 μg/kg) intravenously on days 1 and 56 if they were (1) willing to take nonopiate pain medications, or (2) had unsatisfactory pain response to opiates. The primary study endpoints were the average change from baseline in pain while walking and the patient's global assessment of response to therapy.Patients (N = 444) were aged 57–60 yr and had similar baseline pain characteristics across all six study groups. All doses of tanezumab were associated with an improvement in pain response. Mean pain reduction from baseline ranged from 31.0 to 45.2 points in the tanezumab groups, compared with 15.5 points in the placebo group (P &lt; 0.001). Increase in patient global assessment of response to therapy also favored the tanezumab groups (16.3–23.7 vs. 9.2 points, respectively; P ≤ 0.001). Improvements were seen as early as 1 week after initiation of therapy. Reductions in overall knee pain were also observed (43–62 vs. 23%, respectively; P &lt; 0.001). Headache (8.9%), upper respiratory infection (7.3%), and paresthesia (6.5%) were the most common adverse events in the tanezumab groups. The highest dose of tanezumab (200 μg/kg) was associated with the most adverse events.Antitumor necrosis factor therapy has produced remarkable benefits in several disease states. This is the first clinical study of anti-NGF therapy in patients. Anti-NGF showed remarkable efficacy against osteoarthritis pain. In general, adverse events were small. The article also notes the recent findings of osteonecrosis in some patients treated with anti-NGF therapy. Although it is possible anti-NGF therapy may have beneficial effects in other clinical pain conditions, concerns regarding adverse events are noted.Chronic migraine is a disabling disorder. For many patients, migraine pain remains refractory to standard treatments, despite recent progress. Subcutaneous occipital nerve stimulation has demonstrated efficacy in patients with headache disorders, including chronic migraines.A prospective, multicenter, randomized, blinded, placebo-controlled feasibility study was conducted to assess preliminary safety and efficacy for occipital nerve stimulation treatment of patients with chronic migraines. Patients were randomly assigned (2:1:1) to receive adjustable stimulation (n = 28), preset stimulation (n = 16), or medical management (n = 17). Patients in the adjustable stimulation group were instructed to keep the stimulator “on” and adjust it as necessary to minimize pain. The preset stimulation group was a control group who received preset stimulation rather than adjustable stimulation. Outcomes were assessed 3 months after implantation.Patients were aged 41–50 yr, with a migraine history of at least 18 yr, and an average chronic migraine headache history of 10 yr. Compared with baseline, all three groups demonstrated reductions in the number of headache days per month (1–9 days) and duration of prolonged severe headaches per month (1–5 days). Overall, pain intensity was also reduced for the adjustable stimulation (1.5 days), preset stimulation (0.5 days), and medical management (0.6 days) groups. Of the 51 patients who had successful implant procedures, 56 adverse effects were observed in 36 patients. There were three serious adverse effects that required hospitalization. Lead migration occurred in 24% of patients.Occipital nerve stimulation, like spinal cord stimulation, has been used to manage chronic headache. This preliminary study demonstrated efficacy of occipital nerve stimulation for chronic migraine headache. An accompanying editorial noted the difficulties in clinical trials and proper controls in these populations and suggests that, based on the positive results from this trial, further studies are needed.Many surgical patients experience chronic postoperative pain. Postoperative pain can be influenced by psychological factors, such as attentional bias for pain-related information. However, this factor has only been studied with acute postoperative pain.A prospective study was conducted to determine whether attentional and emotional mechanisms of pain processing predict long-term postoperative pain in patients undergoing chest malformation corrective surgeries. Men with congenital malformations of the thorax and without a history of chronic pain conditions, major surgery, or psychological disorders were included (N = 84). Outcomes were assessed at baseline and at 3 and 6 months after surgery.Twenty-five percent of patients had postoperative pain at 3 months and 14% at 6 months. High pain-related disability was found in 54% of patients at 3 months and 13% at 6 months. Positive words, assessed in the dot-probe task (d = 0.5074 and 0.6475, respectively), and morning cortisol concentration (d = 0.6615 and 0.5074, respectively) were potent predictors of pain intensity. Multivariate analysis confirmed that attentional preference for positive words (6 months; P = 0.031), temporal summation of heat pain (3 months; P = 0.025), and heat pain thresholds (3 months; P = 0.028) were significant predictors for pain intensity after surgery. The Pain Vigilance and Awareness Questionnaire was also found to be a predictor for pain-related disability at 3 and 6 months (d = 0.7131 and 0.5237, respectively).Chronic pain after surgery is receiving greater attention. In this prospective study of young men undergoing pectus repair, a variable in the Pain Vigilance and Awareness Questionnaire predicted those with persistent pain. Other factors measured before surgery that predicted chronic pain were an attentional bias towards positive stimuli, and low pressure and high cold pain thresholds.