Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients.

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).

Rapid Assessment and Containment of Candida auris Transmission in Postacute Care Settings-Orange County, California, 2019.

BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Endovascular Interventions for Femoropopliteal Peripheral Artery Disease: A Network Meta-Analysis of Current Technologies.

PURPOSE: To use network meta-analysis (NMA) to determine the optimal endovascular strategy for management of femoropopliteal peripheral artery disease (PAD) given the lack of multiple prospective randomized trials to guide treatment decisions. MATERIALS AND METHODS: NMA is a new meta-analytic method that permits comparisons among any 2 therapies by combining results of a collection of clinical trials conducted in the same or similar patient population. NMA was used to analyze data from 15 randomized controlled trials (RCTs) and 10 prospective, multicenter, single-arm trials (combined evidence [CE] NMA) that evaluated target lesion revascularization (TLR) for 5 endovascular strategies: bare metal stent (BMS), polymer-covered metal stent (CMS), drug-eluting stent (DES), drug-coated balloon (DCB) and percutaneous transluminal angioplasty (PTA). RESULTS: The RCT and CE NMAs included 2,912 (6,091) patients with 3,151 (6,786) person-years of follow-up. In the CE NMA, DCB provided a statistically significant 68% reduction in TLR compared with PTA and a statistically significant 53% reduction in TLR compared with BMS. BMS, CMS, and DES provided reductions in TLR of 33%, 48%, and 58% compared with PTA, with statistical significance achieved for CMS and DES. The significant reductions in TLR for DCB compared with PTA and BMS were replicated in the RCT NMA. CONCLUSIONS: This NMA demonstrated that DCB provided better reduction in TLR rates compared with PTA and BMS.

Rheolytic Pharmacomechanical Thrombectomy for the Management of Acute Limb Ischemia: Results From the PEARL Registry.

PURPOSE: To present the results of rheolytic pharmacomechanical thrombectomy (PMT) for the management of acute limb ischemia (ALI) as reported in the PEARL Registry (PEripheral Use of AngioJet Rheolytic Thrombectomy with a variety of catheter Lengths). METHODS: A total of 283 patients (mean age 65±13 years; 170 men) presenting with ALI undergoing treatment with the AngioJet System at participating institutions were enrolled in the registry. Rutherford ALI categories included 26% with viable limbs, 38% with marginally threatened limbs, 35% with immediately threatened limbs, and <1% with irreversible damage. Procedure and follow-up data were collected for the calculation of outcomes. To control for patient selection bias, propensity score matching was used to compare outcomes for patients undergoing PMT with or without catheter-directed thrombolysis (CDT). RESULTS: Procedure success was achieved in 235 (83%) of 283 patients. Half of the procedures (147, 52%) were completed without the need for adjunctive CDT. At 12-month follow-up, amputation-free survival and freedom from mortality were 81% and 91%, respectively; 12-month freedom from bleeding requiring transfusion was 91%, and freedom from renal failure was 95%. Subgroup analysis revealed significantly better outcomes in patients without infrapopliteal involvement and those who underwent PMT without CDT. In the matched cohorts, higher rates of procedure success, 12-month amputation-free survival, and 12-month freedom from amputation were observed in the PMT without CDT group (88% vs 74%, p=0.021; 87% vs 72%, p=0.028; 96% vs 81%, p=0.01, respectively). CONCLUSIONS: The results support the use of PMT as a first-line treatment for ALI, providing a rapid reperfusion to the extremity, reduced procedure time, and an acceptable risk profile without compromising limb salvage.

N-acetylcysteine plus intravenous fluids versus intravenous fluids alone to prevent contrast-induced nephropathy in emergency computed tomography.

STUDY OBJECTIVE: We test the hypothesis that N-acetylcysteine plus normal saline solution is more effective than normal saline solution alone in the prevention of contrast-induced nephropathy. METHODS: The design was a randomized, double blind, 2-center, placebo-controlled interventional trial. Inclusion criteria were patients undergoing chest, abdominal, or pelvic computed tomography (CT) scan with intravenous contrast, older than 18 years, and at least one contrast-induced nephropathy risk factor. Exclusion criteria were end-stage renal disease, pregnancy, N-acetylcysteine allergy, or clinical instability. Intervention for the treatment group was N-acetylcysteine 3 g in 500 mL normal saline solution as an intravenous bolus and then 200 mg/hour (67 mL/hour) for up to 24 hours; and for the placebo group was 500 mL normal saline solution and then 67 mL/hour for up to 24 hours. The primary outcome was contrast-induced nephropathy, defined as an increase in creatinine level of 25% or 0.5 mg/dL, measured 48 to 72 hours after CT. RESULTS: The data safety and monitoring board terminated the study early for futility. Of 399 patients enrolled, 357 (89%) completed follow-up and were included. The N-acetylcysteine plus saline solution group contrast-induced nephropathy rate was 14 of 185 (7.6%) versus 12 of 172 (7.0%) in the normal saline solution only group (absolute risk difference 0.6%; 95% confidence interval -4.8% to 6.0%). The contrast-induced nephropathy rate in patients receiving less than 1 L intravenous fluids in the emergency department (ED) was 19 of 147 (12.9%) versus 7 of 210 (3.3%) for greater than 1 L intravenous fluids (difference 9.6%; 95% confidence interval 3.7% to 15.5%), a 69% risk reduction (odds ratio 0.41; 95% confidence interval 0.21 to 0.80) per liter of intravenous fluids. CONCLUSION: We did not find evidence of a benefit for N-acetylcysteine administration to our ED patients undergoing contrast-enhanced CT. However, we did find a significant association between volume of intravenous fluids administered and reduction in contrast-induced nephropathy.

Meta-analysis of clinical efficacy of pulsed radio frequency energy treatment.

OBJECTIVE: To statistically evaluate published clinical efficacy data related to the use of pulsed radio frequency energy (PRFE) therapy in 3 clinical applications. BACKGROUND: Numerous clinical studies have reported efficacy outcomes for PRFE therapy use in the palliative treatment of both postoperative and nonpostoperative pain and edema, and for its use as an adjunctive wound-healing (WH) therapeutic. Although diverse in design and endpoint, these studies are amenable to systematic review using both a vote-counting and P-value combination meta-analytic technique. METHODS: A meta-analysis of efficacy outcomes reported in clinical trials was performed using a vote-counting procedure. In addition, when possible, the sum of logs method of P-value combination was used to determine a significance level for the combined evidence within each endpoint and clinical area. RESULTS: Of the 186 clinical articles identified after application of selection criteria, there were 25 controlled trials that met criteria for inclusion in vote-counting and P-value combination methods and were used for formal statistical analysis. In total, 1332 patients receiving PRFE treatment were studied. Vote-counting procedure applied to clinical outcomes from controlled studies resulted in a greater number of positive outcomes than neutral outcomes, and zero negative outcomes, for each of the clinical application groups evaluated. The sum of logs P-value method found statistically significant improvement in pain, reduction in edema, and improvement in WH outcomes. CONCLUSIONS: On the basis of statistical evaluation of published clinical efficacy data, there is strong statistical evidence that PRFE therapy is effective in the treatment of postoperative and nonpostoperative pain and edema and in WH applications.

Diaphragm pacing improves sleep in patients with amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) patients, respiratory insufficiency is a major burden. Diaphragm conditioning by electrical stimulation could interfere with lung function decline by promoting the development of type 1 muscle fibres. We describe an ancillary study to a prospective, non-randomized trial (NCT00420719) assessing the effects of diaphragm pacing on forced vital capacity (FVC). Sleep-related disturbances being early clues to diaphragmatic dysfunction, we postulated that they would provide a sensitive marker. Stimulators were implanted laparoscopically in the diaphragm close to the phrenic motor point in 18 ALS patients for daily conditioning. ALS functioning score (ALSFRS), FVC, sniff nasal inspiratory pressure (SNIP), and polysomnographic recordings (PSG, performed with the stimulator turned off) were assessed before implantation and after four months of conditioning (n = 14). Sleep efficiency improved (69 ± 15% to 75 ± 11%, p = 0.0394) with fewer arousals and micro-arousals. This occurred against a background of deterioration as ALSFRS-R, FVC, and SNIP declined. There was, however, no change in NIV status or the ALSFRS respiratory subscore, and the FVC decline was mostly due to impaired expiration. Supporting a better diaphragm function, apnoeas and hypopnoeas during REM sleep decreased. In conclusion, in these severe patients not expected to experience spontaneous improvements, diaphragm conditioning improved sleep and there were hints at diaphragm function changes.

The association of near-infrared spectroscopy-derived tissue oxygenation measurements with sepsis syndromes, organ dysfunction and mortality in emergency department patients with sepsis.

INTRODUCTION: Near-infrared spectroscopy (NIRS) noninvasively measures peripheral tissue oxygen saturation (StO2). NIRS may be utilized along with a vascular occlusion test, in which limb blood flow is temporarily occluded and released, to quantify a tissue bed's rate of oxygen exchange during ischemia and recovery. The objective of this study was to test the hypothesis that NIRS-derived StO2 measures (StO2 initial, StO2 occlusion and StO2 recovery) identify patients who are in shock and at increased risk of organ dysfunction (Sequential Organ Failure Assessment (SOFA) score ≥ 2 at 24 hours) and dying in the hospital. METHODS: This prospective, observational study comprised a convenience sample of three cohorts of adult patients (age > 17 years) at three urban university emergency departments: (1) a septic shock cohort (systolic blood pressure < 90 after fluid challenge; the "SHOCK" cohort, n = 58), (2) a sepsis without shock cohort (the "SEPSIS" cohort, n = 60) and emergency department patients without infection (n = 50). We measured the StO2 initial, StO2 occlusion and StO2 recovery slopes for all patients. Outcomes were sepsis syndrome severity, organ dysfunction (SOFA score at 24 hours) and in-hospital mortality. RESULTS: Among the 168 patients enrolled, mean initial StO2 was lower in the SHOCK cohort than in the SEPSIS cohort (76% vs 81%), with an impaired occlusion slope (-10.2 and 5.2%/minute vs -13.1 and 4.4%/minute) and an impaired recovery slope (2.4 and 1.6%/second vs 3.9 and 1.7%/second) (P < 0.001 for all). The recovery slope was well-correlated with SOFA score at 24 hours (-0.35; P < 0.001), with a promising area under the curve (AUC) for mortality of 0.81. The occlusion slope correlation with SOFA score at 24 hours was 0.21 (P < 0.02), with a fair mortality AUC of 0.70. The initial StO2 was significantly but less strongly correlated with SOFA score at 24 hours (-0.18; P < 0.04), with a poor mortality AUC of 0.56. CONCLUSIONS: NIRS measurements for the StO2 initial, StO2 occlusion and StO2 recovery slope were abnormal in patients with septic shock compared to sepsis patients. The recovery slope was most strongly associated with organ dysfunction and mortality. Further validation is warranted. TRIAL REGISTRATION: NCT01062685.

Continuous noninvasive tissue oximetry in the early evaluation of the combat casualty: a prospective study.

BACKGROUND: We hypothesized that near-infrared spectroscopy (NIRS)-derived tissue oxygenation saturation (StO2) could assist in identifying shock in casualties arriving to a combat support hospital and predict the need for life-saving interventions (LSIs) and blood transfusions. METHODS: We performed a prospective observational trial at a single US Army combat support hospital in Iraq from August to December 2007. Arriving casualties had NIRS-derived StO2 recorded in the emergency department. Minimum (StO2 min) and initial 2-minute averaged StO2 and tissue hemoglobin index readings were used as end points. Outcomes measured were requirement for LSIs, any blood transfusion, massive transfusion (>10 units in 24 hours), and early mortality. The data were subjected to univariate and multivariate logistic regression modeling. RESULTS: Of the 147 combat casualties enrolled in the trial, 72 (49%) required an LSI, 42 (29%) required blood transfusion, and 10 (7%) required massive transfusion. On multivariate logistic regression analysis of the whole study group, systolic blood pressure (SBP), international normalized ratio, tissue hemoglobin index, and hematocrit predicted blood transfusion with an area under the curve of 0.90 (0.84-0.96), with a confidence interval of 95%. When just the group with an SBP >90 was analyzed, independent predictors of patients requiring blood transfusion on logistic regression analysis were StO2 min (odds ratio of 1.35) and hematocrit (odds ratio of 2.66) for an area under the curve of 0.84 (0.76-0.92). CONCLUSIONS: NIRS-derived StO2 obtained on arrival predicts the need for blood transfusion in casualties who initially seem to be hemodynamically stable (SBP >90). Further study of this technology for use in the resuscitation of trauma patients is warranted.

Early hypothermia in severely injured trauma patients is a significant risk factor for multiple organ dysfunction syndrome but not mortality.

OBJECTIVE: To evaluate the relationship of early hypothermia to multiple organ failure and mortality in a prospectively-collected database of severely injured trauma patients. METHODS: This prospective observational study was performed at 7 level I trauma centers over a 16-month period. Severely injured trauma patients with signs of hypoperfusion (eg, base deficit, hypotension) and need for blood transfusion during their early hospital course were followed for 24 hours with near infrared spectroscopy-derived tissue oxygen saturation (StO2) and other variables for 28 days to evaluate outcomes including multiple organ dysfunction syndrome (MODS) and death. Early hypothermia was defined as the presence of a temperature <35°C [corrected] anytime within the first 6 hours of hospitalization. Comparisons between groups were made using the Wilcoxon Two-Sample test for continuous variables and either the Fisher exact or chi2 test for categorical variables. Multivariate logistic regression was utilized to understand the effect of hypothermia on outcome (MODS and mortality). RESULTS: Hypothermia was very common in this cohort of patients, present in 43% of patients enrolled (155/359). Hypothermic patients were 3 times more likely than normothermic patients to develop MODS (21% vs. 9%, P = 0.003). Hypothermic patients did not have an increased incidence of mortality (16% vs. 12%, P= 0.2826). Base deficit in hypothermic patients did not discriminate between patients who did or did not develop MODS (9.8 +/- 4.6 mEq/L vs. 9.4 +/- 4.4 mEq/L). In contrast, base deficit in hypothermic patients discriminated with respect to mortality (14.6 +/- 7.2 mEq/L versus 9.5 +/- 4.5 mEq/L; P 0.0021), but this effect was not observed in normothermic patients [corrected]. Significant predictors of MODS using multivariate analysis included minimum StO2 (P= 0.0014) and hypothermia (P = 0.0371). Predictors for mortality using multivariate analysis included minimum StO2 (P= 0.0021) and base deficit (P= 0.0454), but not hypothermia (P= 0.5289). Hypothermia remained a significant risk factor for MODS when systolic blood pressure, volume of fluid, and volume of blood infused were included in the multivariate model. CONCLUSION: Hypothermia is common in severely injured trauma patients (nearly half of patients in this series) and is a significant risk factor for MODS but not mortality. The predictive value of base deficit for development of MODS is blunted in the presence of hypothermia. A low StO2 value predicts MODS and mortality in trauma patients and is a durable measure in both normothermic and hypothermic patient groups.

Propensity Score-Adjusted Comparison of Long-Term Outcomes Among Revascularization Strategies for Critical Limb Ischemia.

BACKGROUND: Few studies have compared long-term outcomes among specific treatment modalities for critical limb ischemia. The aim of this study was to compare long-term outcomes with percutaneous transluminal angioplasty (PTA), stent placement, atherectomy, or surgical bypass in patients diagnosed with critical limb ischemia. METHODS: In this observational study using Medicare claims data, we identified incident cases with a primary critical limb ischemia diagnosis who received PTA, stent placement, atherectomy, or surgical bypass. We used propensity score weighting to determine the association of treatment type with all-cause mortality and major (above ankle) amputation over 4 years follow-up. RESULTS: Among 36 860 patients (10 904 PTA; 11 295 stent placement; 4422 atherectomy; 10 239 surgical bypass), all-cause mortality over 4 years was 49.3% with atherectomy, 51.4% with surgical bypass, 53.7% with stent placement, and 54.7% with PTA (P<0.05 for all pairwise comparisons). Major amputation rates over 4 years were 6.8% with atherectomy, 7.8% with stent placement, 8.1% with PTA, and 10.8% with surgical bypass (P<0.05 for all pairwise comparison except PTA versus stent). CONCLUSIONS: Among Medicare beneficiaries who received PTA, stent placement, atherectomy, or surgical bypass for critical limb ischemia, high mortality and major amputation rates were observed with minor differences among treatment groups. Statistically significant group differences of uncertain clinical importance were observed for several comparisons. Results from observational research may be susceptible to bias because of unmeasured confounders and, therefore, these comparative results should be interpreted with caution.

Temporary transvenous diaphragm pacing vs. standard of care for weaning from mechanical ventilation: study protocol for a randomized trial.

BACKGROUND: Mechanical ventilation (MV) is a life-saving technology that restores or assists breathing. Like any treatment, MV has side effects. In some patients it can cause diaphragmatic atrophy, injury, and dysfunction (ventilator-induced diaphragmatic dysfunction, VIDD). Accumulating evidence suggests that VIDD makes weaning from MV difficult, which involves increased morbidity and mortality. METHODS AND ANALYSIS: This paper describes the protocol of a randomized, controlled, open-label, multicenter trial that is designed to investigate the safety and effectiveness of a novel therapy, temporary transvenous diaphragm pacing (TTVDP), to improve weaning from MV in up to 88 mechanically ventilated adult patients who have failed at least two spontaneous breathing trials over at least 7 days. Patients will be randomized (1:1) to TTVDP (treatment) or standard of care (control) groups. The primary efficacy endpoint is time to successful extubation with no reintubation within 48 h. Secondary endpoints include maximal inspiratory pressure and ultrasound-measured changes in diaphragm thickness and diaphragm thickening fraction over time. In addition, observational data will be collected and analyzed, including 30-day mortality and time to discharge from the intensive care unit and from the hospital. The hypothesis to be tested postulates that more TTVDP patients than control patients will be successfully weaned from MV within the 30 days following randomization. DISCUSSION: This study is the first large-scale clinical trial of a novel technology (TTVDP) aimed at accelerating difficult weaning from MV. The technology tested provides the first therapy directed specifically at VIDD, an important cause of delayed weaning from MV. Its results will help delineate the place of this therapeutic approach in clinical practice and help design future studies aimed at defining the indications and benefits of TTVDP. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03096639 . Registered on 30 March 2017.

A Bayesian meta-analysis comparing AngioJet thrombectomy to percutaneous coronary intervention alone in acute myocardial infarction.

OBJECTIVE: The purpose of this meta-analysis was to compare outcomes for AngioJet thrombectomy versus percutaneous coronary intervention (PCI) without thrombectomy in acute myocardial infarction (AMI) patients. BACKGROUND: PCI is the preferred treatment for revascularizing the infarct-related artery in patients with AMI. There is controversy about the benefits of thrombectomy as an adjunct to PCI. METHODS: AMI studies published between January 1, 1999, and March 1, 2007, were used to compare AngioJet thrombectomy plus PCI to PCI alone. Bayesian meta-analytic estimates were used to estimate the odds ratios (95% CI) for short-term mortality, major adverse cardiac events (MACE), and final TIMI 3 flow. RESULTS: The AngioJet data included 11 studies and 1,018 patients. The PCI data included 81 studies and 24,076 patients. The AngioJet group included more patients with large thrombus burden, rescue PCI after failed thrombolytic therapy, and longer symptom duration compared to the PCI group. Despite the higher risk profile of AngioJet patients, the groups had similar odds of short-term mortality, 0.98 (0.53, 1.50), MACE, 1.25 (0.54, 2.40), and final TIMI 3 flow, 1.12 (0.70, 2.27). CONCLUSION: AngioJet thrombectomy results in clinical and angiographic outcomes that are similar to PCI in lower risk AMI patients. These observations suggest that AngioJet thrombectomy may reduce the additional risk associated with visible thrombus in the infarct-related lesion.

Massive transfusion in trauma patients: tissue hemoglobin oxygen saturation predicts poor outcome.

BACKGROUND: Severely bleeding trauma patients requiring massive transfusion (MT) often experience poor outcomes. Our purpose was to determine the potential role of near infrared spectrometry derived tissue hemoglobin oxygen saturation (StO2) monitoring in early prediction of MT, and in the identification of those MT patients who will have poor outcomes. METHODS: Data from a prospective multi-institution StO2 monitoring study were analyzed to determine the current epidemiology of MT (defined as transfusion volume >/=10 units packed red blood cells in 24 hours of hospitalization). Multivariate logistic regression was used to develop prediction models. RESULTS: Seven US level I trauma centers (TC) enrolled 383 patients. 114 (30%) required MT. MT progressed rapidly (40% exceeded MT threshold 2 hours after TC arrival, 80% after 6 hours). One third of MT patients died. Two thirds of deaths were due to early exsanguination and two thirds of early exsanguination patients died within 6 hours. One third of the early MT survivors developed multiple organ dysfunction syndrome. MT could be predicted with standard, readily available clinical data within 30 minutes and 60 minutes of TC arrival (area under the receiver operating characteristic curve = 0.78 and 0.80). In patients who required MT, StO2 was the only consistent predictor of poor outcome (multiple organ dysfunction syndrome or death). CONCLUSION: MT progresses rapidly to significant morbidity and mortality despite level I TC care. Patients who require MT can be predicted early, and persistent low StO2 identifies those MT patients destined to have poor outcome. The ultimate goal is to identify these high risk patients as early as possible to test new strategies to improve outcome. Further validation studies are needed to analyze appropriate allocation and study appropriate use of damage control interventions.

The diagnostic value of intracompartmental pressure measurement, magnetic resonance imaging, and near-infrared spectroscopy in chronic exertional compartment syndrome: a prospective study in 50 patients.

BACKGROUND: Patients with chronic exertional compartment syndrome have pain during exercise that usually subsides at rest. History and physical examination may raise suspicion of the syndrome; diagnosis is usually confirmed with intracompartmental pressure measurement after exercise. Studies have shown that magnetic resonance imaging and near-infrared spectroscopy have diagnostic ability in this syndrome. HYPOTHESIS: Magnetic resonance imaging and near-infrared spectroscopy can be used to diagnose chronic exertional compartment syndrome. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 2. METHODS: Patients were enrolled if there was clinical suspicion of chronic exertional compartment syndrome, and a fasciotomy was performed based on this suspicion. Before fasciotomy, intracompartmental pressure, near-infrared spectroscopy, and magnetic resonance imaging data were collected during and after exercise on a treadmill. Near-infrared spectroscopy and intracompartmental pressure values were recorded in the same manner after fasciotomy. Retrospective proof that diagnosis of the syndrome had been correct was the absence of exertional complaints from the preoperative examination during exercise at postfasciotomy visit. RESULTS: Fifty patients (100 legs) participated in the prefasciotomy visit; 3 refused fasciotomy; 2 were lost to follow-up. Of 45 patients who completed the postfasciotomy visit, the diagnosis of chronic exertional compartment syndrome was retrospectively confirmed in 42 patients and discarded in 3 patients. The sensitivity for intracompartmental pressure (cutoff point, 35 mmHg) found in this study was 77% (67%-86%, exact 95% confidence interval), lower than estimates from the literature (93%). The sensitivity (previously defined cutoff) for near-infrared spectroscopy was 85% (76%-92%, exact 95% confidence interval), validating the estimate found in the literature (85%). Sensitivity of magnetic resonance imaging was comparable to that of intracompartmental pressure and near-infrared spectroscopy; associated specificity at a given sensitivity appeared to be lower with magnetic resonance imaging. CONCLUSION: This study validates the sensitivity of near-infrared spectroscopy and provides estimates for the sensitivity and specificity of magnetic resonance imaging in chronic exertional compartment syndrome in a large group of patients. The sensitivity of noninvasive near-infrared spectroscopy is clinically equivalent to that of invasive intracompartmental pressure measurements.

Cost-effectiveness of three treatment strategies for lumbar spinal stenosis: Conservative care, laminectomy, and the Superion interspinous spacer.

BACKGROUND: Lumbar spinal stenosis is a painful and debilitating condition resulting in healthcare costs totaling tens of billions of dollars annually. Initial treatment consists of conservative care modalities such as physical therapy, NSAIDs, opioids, and steroid injections. Patients refractory to these therapies can undergo decompressive surgery, which has good long-term efficacy but is more traumatic and can be associated with high post-operative adverse event (AE) rates. Interspinous spacers have been developed to offer a less-invasive alternative. The objective of this study was to compare the costs and quality adjusted life years (QALYs) gained of conservative care (CC) and decompressive surgery (DS) to a new minimally-invasive interspinous spacer. METHODS: A Markov model was developed evaluating 3 strategies of care for lumbar spinal stenosis. If initial therapies failed, the model moved patients to more invasive therapies. Data from the Superion FDA clinical trial, a prospective spinal registry, and the literature were used to populate the model. Direct medical care costs were modeled from 2014 Medicare reimbursements for healthcare services. QALYs came from the SF-12 PCS and MCS components. The analysis used a 2-year time horizon with a 3% discount rate. RESULTS: CC had the lowest cost at $10,540, while Spacers and DS were nearly identical at about $13,950. CC also had the lowest QALY increase (0.06), while Spacers and DS were again nearly identical (.28). The incremental cost-effectiveness ratios (ICER) for Spacers compared to CC was $16,300 and for DS was $15,200. CONCLUSIONS: Both the Spacer and DS strategies are far below the commonly cited $50,000/QALY threshold and produced several times the QALY increase versus CC, suggesting that surgical care provides superior value (cost / effectiveness) versus sustained conservative care in the treatment of lumbar spinal stenosis.

Low StO2 measurements in surgical intensive care unit patients is associated with poor outcomes.

BACKGROUND: Near-infrared spectroscopy-derived tissue hemoglobin saturation (StO2) is a noninvasive measurement that reflects changes in microcirculatory tissue perfusion. Previous studies in trauma patients have shown a correlation between low StO2 levels and mortality, organ failure, and severity of injury. The goals of this study were to identify the incidence of low StO2 in the critically ill patient population of a surgical intensive care unit (SICU) and evaluate the relationship of low StO2 and clinical outcomes. METHODS: We conducted a prospective cohort study at the University of Minnesota Medical Center. After institutional review board approval, 620 patients admitted to the SICU between July 2010 and July 2011 were screened for enrollment. Patients with an expected ICU length of stay of less than 24 hours were excluded. In the 490 patients who met inclusion criteria, StO2 measurements were obtained from the thenar eminence one to three times daily for the length of the ICU stay, up to 14 days. Outcome data included 28-day hospital mortality; ICU readmission; ventilator-free, ICU-free, and hospital-free days; and the need for lifesaving interventions. RESULTS: The overall incidence of low StO2 (<70%) was 11% of the patients per day. Patients with at least 1 day in the SICU with an StO2 measurement of less than 70% had higher rates of ICU readmission and fewer ventilator-free, ICU-free, and hospital-free days compared with those who did not. Mortality (28-day in-hospital) trended higher for these patients but was not statistically significant. An increase in the number of days with StO2 less than 70% was also associated with fewer ventilator-free, ICU-free, and hospital-free days. CONCLUSION: Low StO2 (<70%) is common and associated with poor outcomes in SICU patients. Near-infrared spectroscopy represents a potentially useful, noninvasive adjunct to monitoring of critically ill patients. LEVEL OF EVIDENCE: Prognostic study, level II.

The association of near infrared spectroscopy-derived StO2 measurements and biomarkers of endothelial activation in sepsis.

Near infrared spectroscopy (NIRS) may be utilized in conjunction with a vascular occlusion test to quantify a tissue bed's ability to re-oxygenate by measuring continuous tissue oxygen saturation recovery rate. We hypothesize that NIRS recovery slope will be associated with expression of endothelial biomarkers, thus, making it a feasible bedside surrogate for assessing endothelial activation/dysfunction in patients with sepsis. A secondary analysis of a prospective, multicenter, observational study was done on a convenience sample of adult patients at four university emergency departments consisting of patients with septic shock, sepsis without shock and patients without infection. At enrollment we measured the NIRS-derived measurements and collected plasma to assay biomarkers of endothelial activation. 186 patients were enrolled in the study. The mean age was 63 (± 16) years with 60 % male gender. Univariate analysis assessing the linear relationship between the recovery slope with endothelial biomarkers, found a weak but statistical significant association between NIRS recovery slope and soluble fms-like tyrosine kinase-1 (sFLT-1) and tPAI-1 (r = -0.08, p < 0.0001 and r = -0.06, p = 0.002). When adjusting for diabetes, age and sequential organ failure assessment score at enrollment, only sFLT-1 persisted having a statistically significant association (r = -0.04, p = 0.01). We found a weak, but statistically significant relationship between NIRS-derived measurements and biomarkers of endothelial activation/dysfunction in patients with sepsis. This study fails to support the use of NIRS-derived measurements as a clinical or research tool to identify patients with endothelial cell activation/dysfunction and informs researchers that this is not a robust option for identifying this lesion at the bedside.

Is there a role for aggressive use of fresh frozen plasma in massive transfusion of civilian trauma patients?

BACKGROUND: Damage control resuscitation (DCR) with early plasma in combat casualties requiring massive transfusion (MT) decreases early deaths from bleeding. METHODS: To ascertain the potential role of early plasma DCR in civilian MT, we queried a prospective traumatic shock database of 383 civilians. RESULTS: Ninety-three (24%) of the traumatic shock civilians received a MT, of which 26 (28%) died early, predominantly from bleeding within 6 hours. Comparatively, this early MT death cohort arrived in more severe shock and were coagulopathic (mean INR 2.4). In the critical period of MT (ie, the first 3 hours), these patients received 20 U of packed red blood cells (PRBCs) but only 4 U of fresh frozen plasma (FFP). They remained severely acidotic and their coagulopathy worsened as they exsanquinated. CONCLUSION: Civilians who arrived in traumatic shock, required a MT, and died early had worsening coagulopathy, which was not treated. DCR with FFP may have a role in civilian trauma.

Tolerability and infusion time of an accelerated infusion dobutamine echocardiography protocol.

OBJECTIVES: A new, accelerated dobutamine-atropine stress echocardiography (DASE) protocol (baseline 20 mcg/kg/min; 40 mcg/kg/min) was compared with a standard protocol in patients with suspected coronary artery disease (CAD) to evaluate tolerability, length of infusion, and overall test times, as well as safety. METHODS: Patients received the DASE or the standard protocol on an alternating basis (n = 164). RESULTS: Total test time, including patient recovery (HR < 100 bpm), dropped from an average of 19:23-12:12 min (p < 0.0001). Average symptom duration decreased from 5:50 to 3:17 min (p < 0.01). Women had shorter total test times in both accelerated and standard protocols compared to that of men. CONCLUSIONS: The accelerated DASE protocol is a well tolerated alternative to standard dobutamine stress testing allowing practitioners to reduce test times without increasing the incidence of arrhythmias. Patients in the accelerated arm also had shorter duration of symptoms.