Early Beta-Blocker Utilization in Critically Ill Patients With Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: There is limited evidence that beta-blockers may provide benefit for patients with moderate-severe traumatic brain injury (TBI) during the acute injury period. Larger studies on utilization patterns and impact on outcomes in clinical practice are lacking. OBJECTIVE: The present study uses a large, national hospital claims-based dataset to examine early beta-blocker utilization patterns and its association with clinical outcomes among critically ill patients with moderate-severe TBI. METHODS: We conducted a retrospective cohort study of the administrative claims Premier Healthcare Database of adults (≥17 years) with moderate-severe TBI admitted to the intensive care unit (ICU) from 2016 to 2020. The exposure was receipt of a beta-blocker during day 1 or 2 of ICU stay (BB+). The primary outcome was hospital mortality, and secondary outcomes were: hospital length of stay (LOS), ICU LOS, discharge to home, and vasopressor utilization. In a sensitivity analysis, we explored the association of beta-blocker class (cardioselective and noncardioselective) with hospital mortality. We used propensity weighting methods to address possible confounding by treatment indication. RESULTS: A total of 109 665 participants met inclusion criteria and 39% (n = 42 489) were exposed to beta-blockers during the first 2 days of hospitalization. Of those, 42% received cardioselective only, 43% received noncardioselective only, and 14% received both. After adjustment, there was no association with hospital mortality in the BB+ group compared to the BB- group (adjusted odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94, 1.04). The BB+ group had longer hospital stays, lower chance of discharged home, and lower risk of vasopressor utilization, although these difference were clinically small. Beta-blocker class was not associated with hospital mortality. CONCLUSION: In this retrospective cohort study, we found variation in use of beta-blockers and early exposure was not associated with hospital mortality. Further research is necessary to understand the optimal type, dose, and timing of beta-blockers for this population.

Association of Early Dexmedetomidine Utilization With Clinical Outcomes After Moderate-Severe Traumatic Brain Injury: A Retrospective Cohort Study.

BACKGROUND: Traumatic brain injury (TBI) is an expensive and common public health problem. Management of TBI oftentimes includes sedation to facilitate mechanical ventilation (MV) for airway protection. Dexmedetomidine has emerged as a potential candidate for improved patient outcomes when used for early sedation after TBI due to its potential modulation of autonomic dysfunction. We examined early sedation patterns, as well as the association of dexmedetomidine exposure with clinical and functional outcomes among mechanically ventilated patients with moderate-severe TBI (msTBI) in the United States. METHODS: We conducted a retrospective cohort study using data from the Premier dataset and identified a cohort of critically ill adult patients with msTBI who required MV from January 2016 to June 2020. msTBI was defined by head-neck abbreviated injury scale (AIS) values of 3 (serious), 4 (severe), and 5 (critical). We described early continuous sedative utilization patterns. Using propensity-matched models, we examined the association of early dexmedetomidine exposure (within 2 days of intensive care unit [ICU] admission) with the primary outcome of hospital mortality and the following secondary outcomes: hospital length of stay (LOS), days on MV, vasopressor use after the first 2 days of admission, hemodialysis (HD) after the first 2 days of admission, hospital costs, and discharge disposition. All medications, treatments, and procedures were identified using date-stamped hospital charge codes. RESULTS: The study population included 19,751 subjects who required MV within 2 days of ICU admission. The patients were majority male and white. From 2016 to 2020, the annual percent utilization of dexmedetomidine increased from 4.05% to 8.60%. After propensity score matching, early dexmedetomidine exposure was associated with reduced odds of hospital mortality (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.47-0.74; P < .0001), increased risk for liberation from MV (hazard ratio [HR], 1.20; 95% CI, 1.09-1.33; P = .0003), and reduced LOS (HR, 1.11; 95% CI, 1.01-1.22; P = .033). Exposure to early dexmedetomidine was not associated with odds of HD (OR, 1.14; 95% CI, 0.73-1.78; P = .56), vasopressor utilization (OR, 1.10; 95% CI, 0.78-1.55; P = .60), or increased hospital costs (relative cost ratio, 1.98; 95% CI, 0.93-1.03; P = .66). CONCLUSIONS: Dexmedetomidine is being utilized increasingly as a sedative for mechanically ventilated patients with msTBI. Early dexmedetomidine exposure may lead to improved patient outcomes in this population.

Association of Early Dexmedetomidine Utilization With Clinical and Functional Outcomes Following Moderate-Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVE: To examine early sedation patterns, as well as the association of dexmedetomidine exposure, with clinical and functional outcomes among mechanically ventilated patients with moderate-severe traumatic brain injury (msTBI). DESIGN: Retrospective cohort study with prospectively collected data. SETTING: Eighteen Level-1 Trauma Centers, United States. PATIENTS: Adult (age > 17) patients with msTBI (as defined by Glasgow Coma Scale < 13) who required mechanical ventilation from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using propensity-weighted models, we examined the association of early dexmedetomidine exposure (within the first 5 d of ICU admission) with the primary outcome of 6-month Glasgow Outcomes Scale Extended (GOS-E) and the following secondary outcomes: length of hospital stay, hospital mortality, 6-month Disability Rating Scale (DRS), and 6-month mortality. The study population included 352 subjects who required mechanical ventilation within 24 hours of admission. The initial sedative medication was propofol for 240 patients (68%), midazolam for 59 patients (17%), ketamine for 6 patients (2%), dexmedetomidine for 3 patients (1%), and 43 patients (12%) never received continuous sedation. Early dexmedetomidine was administered in 77 of the patients (22%), usually as a second-line agent. Compared with unexposed patients, early dexmedetomidine exposure was not associated with better 6-month GOS-E (weighted odds ratio [OR] = 1.48; 95% CI, 0.98-2.25). Early dexmedetomidine exposure was associated with lower DRS (weighted OR = -3.04; 95% CI, -5.88 to -0.21). In patients requiring ICP monitoring within the first 24 hours of admission, early dexmedetomidine exposure was associated with higher 6-month GOS-E score (OR 2.17; 95% CI, 1.24-3.80), lower DRS score (adjusted mean difference, -5.81; 95% CI, -9.38 to 2.25), and reduced length of hospital stay (hazard ratio = 1.50; 95% CI, 1.02-2.20). CONCLUSION: Variation exists in early sedation choice among mechanically ventilated patients with msTBI. Early dexmedetomidine exposure was not associated with improved 6-month functional outcomes in the entire population, although may have clinical benefit in patients with indications for ICP monitoring.

Association of Early Beta-Blocker Exposure and Functional Outcomes in Critically Ill Patients With Moderate to Severe Traumatic Brain Injury: A Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study.

OBJECTIVES: We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN: Retrospective cohort study. SETTING: ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS: Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of <13) were admitted to the ICU after a blunt TBI. INTERVENTIONS: None. MEASUREMENTS: Primary exposure was a beta blocker during the first 7 days in the ICU, with a primary outcome of 6-month Glasgow Outcome Scale-Extended (GOSE). Secondary outcomes included: length of hospital stay, in-hospital mortality, 6-month and 12-month mortality, 12-month GOSE score, and 6-month and 12-month measures of disability, well-being, quality of life, and life satisfaction. MAIN RESULTS: Of the 450 eligible participants, 57 (13%) received early beta blockers (BB+ group). The BB+ group was on average older, more likely to be on a preinjury beta blocker, and more likely to have a history of hypertension. In the BB+ group, 34 participants (60%) received metoprolol only, 19 participants (33%) received propranolol only, 3 participants (5%) received both, and 1 participant (2%) received atenolol only. In multivariable regression, there was no difference in the odds of a higher GOSE score at 6 months between the BB+ group and BB- group (odds ratio = 0.86; 95% CI, 0.48-1.53). There was no association between BB exposure and secondary outcomes. CONCLUSIONS: About one-sixth of subjects in our study received early beta blockers, and within this group, dose, and timing of beta-blocker administration varied substantially. No significant differences in GOSE score at 6 months were demonstrated, although our ability to draw conclusions is limited by overall low total doses administered compared with prior studies.

Predicting Early Seizures After Intracerebral Hemorrhage with Machine Learning.

BACKGROUND: Seizures are a harmful complication of acute intracerebral hemorrhage (ICH). "Early" seizures in the first week after ICH are a risk factor for deterioration, later seizures, and herniation. Ideally, seizure medications after ICH would only be administered to patients with a high likelihood to have seizures. We developed and validated machine learning (ML) models to predict early seizures after ICH. METHODS: We used two large datasets to train and then validate our models in an entirely independent test set. The first model ("CAV") predicted early seizures from a subset of variables of the CAVE score (a prediction rule for later seizures)-cortical hematoma location, age less than 65 years, and hematoma volume greater than 10 mL-whereas early seizure was the dependent variable. We attempted to improve on the "CAV" model by adding anticoagulant use, antiplatelet use, Glasgow Coma Scale, international normalized ratio, and systolic blood pressure ("CAV + "). For each model we used logistic regression, lasso regression, support vector machines, boosted trees (Xgboost), and random forest models. Final model performance was reported as the area under the receiver operating characteristic curve (AUC) using receiver operating characteristic models for the test data. The setting of the study was two large academic institutions: institution 1, 634 patients; institution 2, 230 patients. There were no interventions. RESULTS: Early seizures were predicted across the ML models by the CAV score in test data, (AUC 0.72, 95% confidence interval 0.62-0.82). The ML model that predicted early seizure better in the test data was Xgboost (AUC 0.79, 95% confidence interval 0.71-0.87, p = 0.04) compared with the CAV model AUC. CONCLUSIONS: Early seizures after ICH are predictable. Models using cortical hematoma location, age less than 65 years, and hematoma volume greater than 10 mL had a good accuracy rate, and performance improved with more independent variables. Additional methods to predict seizures could improve patient selection for monitoring and prophylactic seizure medications.

Simulation-Based Mastery Learning Improves Ultrasound-Guided Peripheral Intravenous Catheter Insertion Skills of Practicing Nurses.

INTRODUCTION: Difficult intravenous (IV) access (DIVA) is frequently encountered in the hospital setting. Ultrasound-guided peripheral IV catheter (USGPIV) insertion has emerged as an effective procedure to establish access in patients with DIVA. Despite the increased use of USGPIV, little is known about the optimal training paradigms for bedside nurses. Therefore, we developed and evaluated a novel, sustainable, USGPIV simulation-based mastery learning (SBML) curriculum for nurses. METHODS: This is a prospective cohort study of an USGPIV SBML training program for bedside nurses over a 12-month period. We evaluated skills and self-confidence before and after training and measured the proportion of the nurses achieving independent, proctor, and instructor status. Procedure logs and surveys were used to explore the nurse experience and utilization of USGPIV on real patients with DIVA 3 months after the intervention. RESULTS: Two hundred thirty-eight nurses enrolled in the study. The USGPIV skill checklist scores increased from median of 6.0 [interquartile range = 4.0-9.0 (pretest) to 29.0, interquartile range = 28-30 (posttest), P < 0.001]. The USGPIV confidence improved from before (mean = 2.32, SD = 1.17) to after (mean = 3.85, SD = 0.73, P < 0.001) training (5-point Likert scale). Sixty-two percent of the nurses enrolled achieved independent status, 47.5% became proctors, and 11.3% course trainers. At 3-month posttraining, the nurses had attempted a mean of 35.6 USGPIV insertions with an 89.5% success rate. CONCLUSIONS: This novel USGPIV SBML curriculum improves nurses' insertion skills, self-confidence, and progresses patient care through USGPIV insertions on hospitalized patients with DIVA.

Transcranial Doppler Ultrasound Evidence of Active Cerebral Embolization in COVID-19.

OBJECTIVE: To report six consecutive patients with confirmed coronavirus disease-2019 (COVID-19) who underwent Transcranial Doppler (TCD) ultrasonography evaluation for cerebral microemboli in the setting of suspected or confirmed acute ischemic stroke. METHODS: Patient data were obtained from medical records from Northwestern Memorial Hospital, Chicago, IL between May and June 2020. All patients with confirmed COVID-19 who underwent clinical TCD ultrasonography for microemboli detection were included. RESULTS: A total of eight TCD studies were performed in six patients with COVID-19 (4 men and 2 women, median age 65±5), four with confirmed ischemic stroke and two with refractory encephalopathy. Microemboli were detected in three male patients, two patients had suffered a confirmed ischemic stroke and one who developed prolonged encephalopathy. Microemboli of varying intensity were identified in multiple vascular territories in two patients, and microemboli persisted despite therapeutic anticoagulation in a third patient. Of the three patients without evidence of microemboli on TCD ultrasonography, two patients had suffered a confirmed ischemic stroke, while one remained with refractory encephalopathy. CONCLUSIONS: TCD ultrasonography for microemboli detection identified three patients with confirmed COVID-19 with evidence of cerebral arterial microemboli, including one who was therapeutically anticoagulated. TCD ultrasonography provides a non-invasive method for evaluating cerebral microemboli in patients with COVID-19 and may be useful in assessing response to treatment in cases with suspected or confirmed disorders of hypercoagulability. Further studies investigating the prevalence of cerebral microemboli and associated risk factors are needed to characterize their pathogenic mechanism and guide therapeutic interventions in hospitalized COVID-19 patients.

Difficult intravenous access in the emergency department: Performance and impact of ultrasound-guided IV insertion performed by nurses.

BACKGROUND: Difficult intravenous access (DIVA) is a common problem in Emergency Departments (EDs), yet the prevalence and clinical impact of this condition is poorly understood. Ultrasound-guided peripheral intravenous catheter (USGPIV) insertion is a successful modality for obtaining intravenous (IV) access in patients with DIVA. OBJECTIVES: We aimed to describe the prevalence of DIVA, explore how DIVA affects delivery of care, and determine if nurse insertion of USGPIV improves care delays among patients with DIVA. METHODS: We retrospectively queried the electronic medical record for all ED patients who had a peripheral IV (PIV) inserted at a tertiary academic medical center from 2015 to 2017. We categorized patients as having DIVA if they required ≥3 PIV attempts or an USGPIV. We compared metrics for care delivery including time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED length of stay (LOS) between patients with and without DIVA. We also compared these metrics in patients with DIVA with a physician-inserted USGPIV versus those with a nurse-inserted USGPIV. RESULTS: A total of 147,260 patients were evaluated during the study period. Of these, 13,192 (8.9%) met criteria for DIVA. Patients with DIVA encountered statistically significant delays in time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED LOS compared to patients without DIVA (all p < 0.001). Patients with nurse-inserted USGPIVs also had statistically significant improvements in time-to-IV-access, time-to-laboratory-results, time-to-IV-analgesia, and ED LOS compared to patients with physician-inserted USGPIVs (all p < 0.001). CONCLUSION: DIVA affects many ED patients and leads to delays in PIV access-related care. Nurse insertion of USGPIVs improves care in patients with DIVA.

Early Stroke Recognition and Time-based Emergency Care Performance Metrics for Intracerebral Hemorrhage.

BACKGROUND AND AIM: Performance measures have been extensively studied for acute ischemic stroke, leading to guideline-established benchmarks. Factors influencing care efficiency for intracerebral hemorrhage (ICH) are not well delineated. We sought to identify factors associated with early recognition of ICH and to assess the association between early recognition and completion of emergency care tasks. METHODS: Consecutive patients with spontaneous ICH were enrolled in an observational cohort study conducted from 2009 to 2017 at an urban comprehensive stroke center, excluding patient transferred from other hospitals. We used stroke team activation as the indicator of early recognition and measured completion times for multiple ICH-relevant performance metrics including door to computed tomography (CT) acquisition and door to hemostatic medication initiation. RESULTS: We studied 204 cases. All stroke-related performance times were faster in patients managed with stroke team activation compared to no activation, including quicker door to CT acquisition (median 24 versus 48 minutes, P < .001) and door to hemostatic medication initiation (63 versus 99 minutes, P = .005). These associations were confirmed in adjusted models. Stroke codes were activated in 43% of cases and were more likely in patients with shorter onset-to-arrival times, higher National Institutes of Health Stroke Scale scores, and higher Glasgow Coma Scale scores. CONCLUSIONS: Stroke team activation was associated with more rapid diagnostic and therapeutic interventions for patients with ICH, but activation did not occur in the majority of cases, implying absence of early recognition. A stroke team activation process improves care performance, but leveraging the advantages of existing systems will require improved triage tools to identify ICH in the acute setting.

Pharmacologic Treatment Reduces Pressure Times Time Dose and Relative Duration of Intracranial Hypertension.

INTRODUCTION: Past work has shown the importance of the "pressure times time dose" (PTD) of intracranial hypertension (intracranial pressure [ICP] > 19 mm Hg) in predicting outcome after severe traumatic brain injury. We used automated data collection to measure the effect of common medications on the duration and dose of intracranial hypertension. METHODS: Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a single, large urban tertiary care facility, were retrospectively enrolled. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. The ICP data were collected automatically at 6-second intervals and averaged over 5 minutes. The percentage of time of intracranial hypertension (PTI) and PTD (mm Hg h) were calculated. RESULTS: A total of 98 patients with 664 treatment instances were identified. Baseline PTD ranged from 27 (before administration of propofol and fentanyl) to 150 mm Hg h (before mannitol). A "small" dose of hypertonic saline (HTS; ≤250 mL 3%) reduced PTD by 38% in the first hour and 37% in the second hour and reduced the time with ICP >19 by 38% and 39% after 1 and 2 hours, respectively. A "large" dose of HTS reduced PTD by 40% in the first hour and 63% in the second (PTI reduction of 36% and 50%, respectively). An increased dose of propofol or fentanyl infusion failed to decrease PTD but reduced PTI between 14% (propofol alone) and 30% (combined increase in propofol and fentanyl, after 2 hours). Barbiturates failed to decrease PTD but decreased PTI by 30% up to 2 hours after administration. All reductions reported are significantly changed from baseline, P < .05. CONCLUSION: Baseline PTD values before drug administration reflects varied patient criticality, with much higher values seen before the use of mannitol or barbiturates. Treatment with HTS reduced PTD and PTI burden significantly more than escalation of sedation or pain management, and this effect remained significant at 2 hours after administration.

Indirect signs of blunt duodenal injury on computed tomography: Is non-operative management safe?

INTRODUCTION: Clear signs of duodenal injury (DI) such as pneumoperitoneum and/or oral contrast extravasation mandate laparotomy. Management when computed tomography (CT) reveals indirect evidence of DI namely duodenal hematoma or periduodenal fluid is unclear. We evaluated the utility of indirect signs to identify DI and the success of expected management, hypothesizing patients with indirect evidence of DI on CT can be safely managed non-operatively. METHODS: We retrospectively reviewed patients with a computed tomography (CT) scan with periduodenal hematoma or periduodenal fluid treated between January 2003 and January 2013 at a level 1 Trauma Center. Demographics, injury characteristics, laboratory values, injury severity scores (ISS), and outcome measures were recorded. Patients having immediate laparotomy were compared to those initially managed nonoperatively. RESULTS: We identified 74 patients with indirect signs of DI, with 35 patients (47%) undergoing immediate operative exploration and 39 (53%) initially managed non-operatively. Lactate (4.5 mg/dL, standard deviation (SD) 2.1 vs 3.1 mg/dL, SD 1.4, p<0.001), ISS (median (IQR) 34 (27-44) vs. 24 (17-34), p=0.002) and abdominal AIS (3 (3-4) vs 2 (2-3), p<0.001) were higher in those with immediate operation. The incidence of DI requiring operative repair was 11% (8 of 74). Six of 35 (17%) explored urgently had a DI requiring repair while 29 of 35 (83%) had no DI or minor injury not requiring surgical therapy. Of those managed non-operatively, 7 of 39 (18%) failed observation but only two (5%) required duodenal repair. There was no significant difference in intensive care unit (ICU) (10.2 days, standard error [SE] 2.1 vs 9.7 days, SE 4.8, p=0.93) or hospital (22.5 days, SE 3.8 vs 23.6 days, SE 8.5, p=0.91) length of stay between those operated on immediately and those that failed non-operative management when adjusted for age, sex, and ISS. There was no mortality in the non-operative group related to an intra-abdominal injury. CONCLUSION: Observation of patients with indirect sign of DI fails in about 20% of patients, but failure rate due to DI is low at 5%. Conservative management in appropriately selected patients is reasonable with close observation.

Predictive value of hyperthermia and intracranial hypertension on neurological outcomes in patients with severe traumatic brain injury.

BACKGROUND: Intracranial hypertension (ICH) and hyperthermia are common after traumatic brain injury (TBI) and associated with worse neurological outcomes. This study sets out to determine the combined power of temperature and intracranial pressure (ICP) for predicting neurologic outcomes and prolonged length of stay (LOS) following severe TBI. METHODS: High resolution (every 6 seconds) temperature and ICP data were collected in adults with severe TBI from 2008-2010. Temperatures were plotted against concurrent ICP and divided based on breakpoints (Temperature: <36, 36-38.5 or >38.5 °C, ICP: <20, 20-30 or >30 mmHg). The percentage of time spent in each section, as well as several pooled unfavourable conditions (hyperthermia ± ICH), were then evaluated for predictive value for ICU-LOS > 7 days and short-term (<6 months) vs. long-term (>6 months) dichotomized neurologic outcomes. RESULTS: Fifty patients were included for analysis with severe TBI. Evaluation of the area under the operating receiver curve (AUC) showed significant periods of fever and high ICP (<30 mmHg) had a strong association with poor long-term neurological outcomes (Day 3, AUC = 0.71, p = 0.04) and were higher than either condition alone. ICU-LOS > 7 days was increased when hyperthermia and/or ICH remained uncontrolled by Day 5 (AUC = 0.82, p = 0.02). SUMMARY: Hyperthermia combined with ICH were shown to be significant prognostic indicators of future poor neurologic outcomes in patients with severe traumatic brain injury.

Origin, Incidence, and Management of Nongynecologic Pelvic Masses Seen on Cross-sectional Imaging.

OBJECTIVE: To characterize the origin of nongynecologic pelvic masses. STUDY DESIGN: Using a radiology database, women who underwent transvaginal ultrasound, CT scan, or MRI for the indication of pelvic mass or pelvic fullness were identified. Demographic information, radiologic data, and outcomes were reviewed. RESULTS: A total of 450 women underwent imaging for the above indications been 2002 and 2012. Of those women, 347 had at least 1 pelvic mass; 3 women had both gynecologic and nongynecologic masses, and 13 women had 2 gynecologic masses. Forty women (12%) had nongynecologic pathology. Of the nongynecologic masses 13 were gastrointestinal in origin, 9 were urologic, and 9 were neuromuscular. Other etiologies included metastatic cancers, iatrogenic masses, and hematologic masses. Seventy-four women had malignant pathology (21%): 17/40 (43%) of nongynecologic pelvic masses and 57/320 (18%) of gynecologic masses (p < 0.05). CONCLUSION: Compared to pelvic masses of gynecologic origin, nongynecologic pelvic masses are more likely to be malignant.

Intracranial pressure response after pharmacologic treatment of intracranial hypertension.

BACKGROUND: The accepted treatment of increased intracranial pressure (ICP) in patients experiencing severe traumatic brain injury is multimodal and algorithmic, obscuring individual effects of treatment. Using continuous vital signs monitoring, we sought to measure treatment effect and ascertain the accuracy of manual data recording. METHODS: Patients older than 17 years, admitted and requiring ICP monitoring between 2008 and 2010 at a high-volume urban trauma center, were retrospectively evaluated. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. ICP data were collected automatically at 6-second intervals and from manual charts. A statistical mixed model was applied to all data to account for multiple sampling. RESULTS: A total of 117 patients met inclusion criteria; 450 treatments were administered when nursing records indicate an ICP greater than 20 mm Hg, while 968 treatments were given when ICP was greater than 20 mm Hg by automated data. Pharmacologic treatments identified include hypertonic saline (HTS), mannitol, barbiturates, and dose escalations of propofol or fentanyl infusions. Treatment with HTS resulted in the largest ICP decrease of the treatments examined, with a 1-hour ICP reduction of 8.8/9.9 mm Hg (for a small/large dose) according to manual data and a reduction of 3.0/2.4 mm Hg according to automated data. Propofol and fentanyl escalations resulted in smaller but significant ICP reductions. Mannitol (n = 8) resulted in statistically insignificant trends down in the first hour but rebounded by the second hour after administration. The average ICP in the hour before medication administration was higher for barbiturates (27 mm Hg) and mannitol (32 mm Hg) than for the other interventions (18-19 mm Hg). CONCLUSION: ICP fell after administration of HTS, mannitol, or barbiturates and showed continued improvement after 2 hours. ICP fell initially after treatment with short-acting propofol and fentanyl but trended back up after 2 hours. Manually recorded data consistently overestimated treatment effectiveness. Automated data collection gives a more accurate assessment of patient status and responsiveness to treatment. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Full of sound and fury, signifying nothing: burden of transient noncritical monitor alarms in a trauma resuscitation unit.

We examined the types of patient monitor alarms encountered in the trauma resuscitation unit of a major level 1 trauma center. Over a 1-year period, 316688 alarms were recorded for 6701 trauma patients (47 alarms/patient). Alarms were more frequent among patients with a Glasgow Coma Scale of 8 or less. Only 2.4% of all alarms were classified as "patient crisis," with the rest in the presumably less critical categories "patient advisory," "patient warning," and "system warning." Nearly half of alarms were ≤5 seconds in duration. In this patient population, a 2-second delay would reduce alarms by 25%, and a delay of 5 seconds would reduce all alarms by 49%.

Pericyte requirement for anti-leak action of angiopoietin-1 and vascular remodeling in sustained inflammation.

Blood vessel leakiness is an early, transient event in acute inflammation but can also persist as vessels undergo remodeling in sustained inflammation. Angiopoietin/Tie2 signaling can reduce the leakiness through changes in endothelial cells. The role of pericytes in this action has been unknown. We used the selective PDGF-B-blocking oligonucleotide aptamer AX102 to determine whether disruption of pericyte-endothelial crosstalk alters vascular leakiness or remodeling in the airways of mice under four different conditions: i) baseline, ii) acute inflammation induced by bradykinin, iii) sustained inflammation after 7-day infection by the respiratory pathogen Mycoplasma pulmonis, or iv) leakage after bradykinin challenge in the presence of vascular stabilization by the angiopoietin-1 (Ang1) mimic COMP-Ang1 for 7 days. AX102 reduced pericyte coverage but did not alter the leakage of microspheres from tracheal blood vessels at baseline or after bradykinin; however, AX102 exaggerated leakage at 7 days after M. pulmonis infection and increased vascular remodeling and disease severity at 14 days. AX102 also abolished the antileakage effect of COMP-Ang1 at 7 days. Together, these findings show that pericyte contributions to endothelial stability have greater dependence on PDGF-B during the development of sustained inflammation, when pericyte dynamics accompany vascular remodeling, than under baseline conditions or in acute inflammation. The findings also show that the antileakage action of Ang1 requires PDGF-dependent actions of pericytes in maintaining endothelial stability.

Angiopoietin-2-driven vascular remodeling in airway inflammation.

Vascular remodeling is a feature of chronic inflammation during which capillaries transform into venules that expand the region of the vasculature in which leakage and leukocyte emigration both occur. Recently, we found that angiopoietin/Tie2 receptor signaling drives the transformation of capillaries into venules at an early stage of the sustained inflammatory response in the airways of mice infected with Mycoplasma pulmonis. However, the precise contributions of both angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) are not clear. In this study, we sought to determine the contribution of Ang2 to this vascular remodeling. Ang2 mRNA expression levels increased and phosphorylated Tie2 immunoreactivity in mucosal blood vessels decreased, indicative of diminished receptor signaling after infection. Selective inhibition of Ang2 throughout the infection by administration of either of two distinct function-blocking antibodies reduced the suppression of Tie2 phosphorylation and decreased the remodeling of mucosal capillaries into venules, the amount of leukocyte influx, and disease severity. These findings are consistent with Ang2 acting as an antagonist of Tie2 receptors and the reduction of Tie2 phosphorylation in endothelial cells rendering the vasculature more responsive to cytokines that promote both vascular remodeling and the consequences of inflammation after M. pulmonis infection. By blocking such changes, Ang2 inhibitors may prove beneficial in the treatment of sustained inflammation in which vascular remodeling, leakage, and leukocyte influx contribute to its pathophysiology.