Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study.

BACKGROUND: Clinicians often encounter agitated patients, and current treatment options include benzodiazepines and antipsychotics. Ketamine rapidly induces dissociation, maintains cardiovascular stability, spontaneous respirations, and airway reflexes. There are no prospective, randomized studies comparing ketamine to other agents in the initial management of acute agitation in the Emergency Department (ED). OBJECTIVE: Determine the efficacy and safety of ketamine compared to parenteral haloperidol plus lorazepam for initial control of acute agitation. METHODS: This study was a prospective, single-institution, randomized, open-label, real world, standard of care pilot study. Adult patients with combative agitation were randomized to ketamine (4 mg/kg IM or 1 mg/kg IV) or haloperidol/lorazepam (haloperidol 5-10 mg IM or IV + lorazepam 1-2 mg IM or IV). The primary outcome was sedation within 5 min, and secondary outcomes included sedation within 15 min, time to sedation, and safety. RESULTS: Ninety three patients were enrolled from January 15, 2018 to October 10, 2018. Significantly more patients who received ketamine compared to haloperidol/lorazepam were sedated within 5 min (22% vs 0%, p = 0.001) and 15 min (66% vs 7%, p < 0.001). The median time to sedation in patients who received ketamine compared to haloperidol/lorazepam was 15 vs 36 min respectively (p < 0.001). Patients who received ketamine experienced a significant, but transient tachycardia (p = 0.01) and hypertension (p = 0.01). CONCLUSION: In patients with combative agitation, ketamine was significantly more effective than haloperidol/lorazepam for initial control of acute agitation, and was not associated with any significant adverse effects.

Validation of the short form of the International Crowding Measure in Emergency Departments: an international study.

OBJECTIVE: There is little consensus on the best way to measure emergency department (ED) crowding. We have previously developed a consensus-based measure, the International Crowding Measure in Emergency Departments. We aimed to externally validate a short form of the International Crowding Measure in Emergency Department (sICMED) against emergency physician's perceptions of crowding and danger. METHODS: We performed an observational validation study in seven EDs in five different countries. We recorded sICMED observations and the most senior available emergency physician's perceptions of crowding and danger at the same time. We performed a times series regression model. RESULTS: A total of 397 measurements were analysed. The sICMED showed moderate positive correlations with emergency physician's perceptions of crowding, r = 0.4110, P < 0.05) and safety (r = 0.4566, P < 0.05). There was considerable variation in the performance of the sICMED between different EDs. The sICMED was only slightly better than measuring occupancy or ED boarding time. CONCLUSION: The sICMED has moderate face validity at predicting clinician's concerns about crowding and safety, but the strength of this validity varies between different EDs and different countries.

Improving emergency department time to provider, left-without-treatment rates, and average length of stay.

BACKGROUND: Emergency Department (ED) overcrowding and ensuing concern about patients who leave without treatment have become a mounting national concern. In addition, the Centers for Medicaid and Medicare Services released regulatory standards for EDs requiring reporting of time from initial triage to decision to admit, as well as actual time of admission. OBJECTIVES: To implement an improved ED patient flow process. METHODS: We performed a comparative, pre- and post-intervention ED redesign study evaluating three primary end points between two similar, seasonal time periods. RESULTS: Despite an 11% increase in daily patient volume in 2010, analysis of time to provider pre-ED redesign and post-ED redesign implementation revealed a mean of 126.7 min in 2009 (SD 37.03) vs. a mean of 26.3 min in 2010 (SD 1.17). The p-value was significant at <0.001. Overall ED average length of stay (ALOS) in 2009 was 5.5 h (SD 0.68) and 3.6 h (SD 1.16) in 2010, reflecting a mean reduction in ALOS of 1.9 h. The p-value was significant at <0.01. The proportion of patients who left without treatment (LWOT) also decreased. The proportion of LWOTs during the 2009 study period was 8.7% (95% confidence interval [CI] 6.14-11.26%), compared to 0.2% (95% CI 0.14-0.36%; p < 0.005) in the 2010 study period. Although the overall ED-visit Press Ganey patient-satisfaction scores improved during the 2010 study period, the results were not statistically significant (p < 0.1). CONCLUSION: Our study demonstrated that a tailored ED redesign process can dramatically decrease the time to provider, ALOS, and LWOT rates.

Communication: partial polarization transfer for single-scan spectroscopy and imaging.

A method is presented to partially transfer nuclear spin polarization from one isotope S to another isotope I by the way of heteronuclear spin couplings, while minimizing the loss of spin order to other degrees of freedom. The desired I spin polarization to be detected is a design parameter, while the sequence of pulses at the two Larmor frequencies is optimized to store the greatest unused S spin longitudinal polarization for subsequent use. The unitary evolution for the case of I(N)S spin systems illustrates the potentially ideal efficiency of this strategy, which is of particular interest when the spin-lattice relaxation time of S greatly exceeds that of I. Explicit timing and pulses are tabulated for the cases for which M ≤ 10 partial transfers each result in equal final polarization of 1/M or more compared to the final I polarization expected in a single transfer for N = 1, 2, or 3 I spins. Advantages for the ratiometric study of reacting molecules and hyperpolarized initial conditions are outlined.

A selective 15N-to-(1)H polarization transfer sequence for more sensitive detection of 15N-choline.

The sensitivity and information content of heteronuclear nuclear magnetic resonance is frequently optimized by transferring spin order of spectroscopic interest to the isotope of highest detection sensitivity prior to observation. This strategy is extended to 15N-choline using the scalar couplings to transfer polarization from 15N to choline's nine methyl 1H spins in high field. A theoretical analysis of a sequence using nonselective pulses shows that the optimal efficiency of this transfer is decreased by 62% as the result of competing 15N-(1)H couplings involving choline's four methylene protons. We have therefore incorporated a frequency-selective pulse to support evolution of only the 15N-methyl 1H coupling during the transfer period. This sequence provides a 52% sensitivity enhancement over the nonselective version in in vitro experiments on a sample of thermally polarized 15N-choline in D2O. Further, the 15N T1 of choline in D2O was measured to be 217+/-38 s, the 15N-methyl 1H coupling constant was found to be 0.817+/-0.001 Hz, and the larger of choline's two 15N-methylene 1H coupling constants was found to be 3.64+/-0.0 1Hz. Possible improvements and applications to in vivo experiments using long-lived hyperpolarized heteronuclear spin order are discussed.

Fast volumetric spatial-spectral MR imaging of hyperpolarized 13C-labeled compounds using multiple echo 3D bSSFP.

PURPOSE: The goal of this work was to develop a fast 3D chemical shift imaging technique for the noninvasive measurement of hyperpolarized (13)C-labeled substrates and metabolic products at low concentration. MATERIALS AND METHODS: Multiple echo 3D balanced steady state magnetic resonance imaging (ME-3DbSSFP) was performed in vitro on a syringe containing hyperpolarized [1,3,3-2H3; 1-(13)C]2-hydroxyethylpropionate (HEP) adjacent to a (13)C-enriched acetate phantom, and in vivo on a rat before and after intravenous injection of hyperpolarized HEP at 1.5 T. Chemical shift images of the hyperpolarized HEP were derived from the multiple echo data by Fourier transformation along the echoes on a voxel by voxel basis for each slice of the 3D data set. RESULTS: ME-3DbSSFP imaging was able to provide chemical shift images of hyperpolarized HEP in vitro, and in a rat with isotropic 7-mm spatial resolution, 93 Hz spectral resolution and 16-s temporal resolution for a period greater than 45 s. CONCLUSION: Multiple echo 3D bSSFP imaging can provide chemical shift images of hyperpolarized (13)C-labeled compounds in vivo with relatively high spatial resolution and moderate spectral resolution. The increased signal-to-noise ratio of this 3D technique will enable the detection of hyperpolarized (13)C-labeled metabolites at lower concentrations as compared to a 2D technique.

Nanoscale torsional resonator for polarization and spectroscopy of nuclear spins.

We propose a torsional resonator that couples to the transverse spin dipole of an attached sample. The absence of relative motion eliminates a source of friction that would otherwise hinder nanoscale implementation. Enhanced spontaneous emission induced by the resonator relaxes the longitudinal spin dipole at a rate of ∼1 s⁻¹ in the low-temperature limit. With signal averaging, single-proton magnetic resonance spectroscopy appears feasible at ∼10 mK and a high magnetic field, while single-shot sensitivity is practical for samples with at least tens of protons in a volume of ∼5 nm³.

Hyperpolarized (1)H NMR employing low gamma nucleus for spin polarization storage.

Here, we demonstrate the utility of low gamma nuclei for spin storage of hyperpolarization followed by proton detection, which theoretically can provide up to approximately (gamma[1H]/gamma[X])(2) gain in sensitivity in hyperpolarized biomedical MR. This is exemplified by hyperpolarized 1-(13)C sites of 2,2,3,3-tetrafluoropropyl 1-(13)C-propionate-d(3) (TFPP), (13)C T(1) = 67 s in D(2)O, and 1-(13)C-succinate-d(2), (13)C T(1) = 105 s in D(2)O, pH 11, using PASADENA. In a representative example, the spin polarization was stored on (13)C for 24 and 70 s, respectively, while the samples were transferred from a low magnetic field polarizer operating at 1.76 mT to a 4.7 T animal MR scanner. Following sample delivery, the refocused INEPT pulse sequence was used to transfer spin polarization from (13)C to protons with an efficiency of 50% for TFPP and 41% for 1-(13)C-succinate-d(2) increasing the overall NMR sensitivity by a factor of 7.9 and 6.5, respectively. The low gamma nuclei exemplified here by (13)C with a T(1) of tens of seconds acts as an efficient spin polarization storage, while J-coupled protons are better for NMR detection.

Small catheter tube thoracostomy: effective in managing chest trauma in stable patients.

BACKGROUND: Image-guided small catheter tube thoracostomy (SCTT) is not currently used as a first-line procedure in the management of patients with chest trauma. We adopted a practice recommendation to use SCTT as a less invasive alternative in the treatment of chest injuries. We reviewed our trauma registry to evaluate our change in practice and the effectiveness of SCTT. METHODS: Retrospective review of all tube thoracostomies (TT) performed in patients with chest injury at a level I trauma center from September 2002 through March 2006. Data collected included age, sex, indications and timing for TT, use of antibiotics, length of stay, complications, and outcomes. Large catheter tube thoracostomy (LCTT) not performed in the operating room or trauma room and all SCTT were deemed nonemergent. RESULTS: There were 565 TT performed in 359 patients. Emergent TT was performed in 252 (70%) and nonemergent TT in 157 (44%) patients, of which 63 (40%) received LCTT and 107 (68%) received SCTT. Although SCTT was performed later after injury than nonemergent LCTT (5.5 days vs. 2.3 days, p < 0.001), average duration of SCTT was shorter (5.5 days vs. 7 days, p < 0.05). Rates of hemothoraces were similarly low for SCTT versus nonemergent LCTT (6.1% vs. 4.2%, p = NS) and rates of residual/recurrent pneumothoraces were not significantly different (8% vs. 14%, p = NS). The rate of occurrence of fibrothorax, however, was significantly lower for SCTT compared with nonemergent LCTT (0% vs. 4.2%, p < 0.05). In patients receiving a single nonemergent TT, SCTT was performed in 55 (61%) and LCTT in 35 (39%). A comparison of these groups revealed that SCTT was performed in older patients (p < 0.05), and was associated with a lower Injury Severity Score (p < 0.05) and shorter length of stay (p = 0.05). SCTT was increasingly used in younger and more seriously injured patients as our experience grew. CONCLUSION: SCTT is effective in managing chest trauma. It is comparable with LCTT in stable trauma patients. This study supports adopting image-guided small catheter techniques in the management of chest trauma in stable patients.

Early intubation in the management of trauma patients: indications and outcomes in 1,000 consecutive patients.

BACKGROUND: The Eastern Association for the Surgery of Trauma Practice Management Guidelines identify indications (EI) for early intubation. However, EI have not been clinically validated. Many intubations are performed for other discretionary indications (DI). We evaluated early intubation to assess the incidence and outcomes of those performed for both EI and DI. METHODS: One thousand consecutive intubations performed in the first 2 hours after arrival at our Level I trauma center were reviewed. Indications, outcomes, and trauma surgeon (TS) intubation rates were evaluated. RESULTS: During a 56-month period, 1,000 (9.9%) of 10,137 trauma patients were intubated within 2 hours of arrival. DI were present in 444 (44.4%) and EI in 556 (55.6%). DI were combativeness or altered mental status in 375 (84.5%), airway or respiratory problems in 21 (4.7%), and preoperative management in 48 (10.8%). Injury Severity Score was 14.6 in DI patients and 22.7 in EI patients (p < 0.001). Predicted versus observed survival was 96.6% versus 95.9% in DI patients and 75.2% versus 75.0% in EI patients (p < 0.001). Head Abbreviated Injury Scale score of >or=3 occurred in 32.7% with DI and 52.0% with EI (p < 0.001). Seven (0.7%) surgical airways were performed; two for DI (0.2%). Eleven (1.1%) patients aspirated during intubation and five (0.5%) suffered oral trauma. There were no other significant complications of intubation for either DI or EI and complication rates were similar in the two groups. Delayed intubation (early intubation after leaving the trauma bay) was required in 67 (6.7%) patients and 59 (88.1%) were for combativeness, neurologic deterioration, or respiratory distress or airway problems. Intubation rates varied among TS from 7.6% to 15.3% (p < 0.001) and rates for DI ranged from 3.3% to 7.4% (p < 0.001). There was a statistically insignificant trend among TS with higher intubation rates to perform fewer delayed intubations. CONCLUSIONS: Early intubation for EI as well as DI was safe and effective. One third of the DI patients had significant head injury. Surgical airways were rarely needed and delayed intubations were uncommon. The intubation rates for EI and DI varied significantly among TSs. The Eastern Association for the Surgery of Trauma Guidelines may not identify all patients who would benefit from early intubation after injury.

PASADENA hyperpolarization of succinic acid for MRI and NMR spectroscopy.

We use the PASADENA (parahydrogen and synthesis allow dramatically enhanced nuclear alignment) method to achieve 13C polarization of approximately 20% in seconds in 1-13C-succinic-d2 acid. The high-field 13C multiplets are observed as a function of pH, and the line broadening of C1 is pronounced in the region of the pK values. The 2JCH, 3JCH, and 3JHH couplings needed for spin order transfer vary with pH and are best resolved at low pH leading to our use of pH approximately 3 for both the molecular addition of parahydrogen to 1-13C-fumaric acid-d2 and the subsequent transfer of spin order from the nascent protons to C1 of the succinic acid product. The methods described here may generalize to hyperpolarization of other carboxylic acids. The C1 spin-lattice relaxation time at neutral pH and 4.7 T is measured as 27 s in H2O and 56 s in D2O. Together with known rates of succinate uptake in kidneys, this allows an estimate of the prospects for the molecular spectroscopy of metabolism.

Towards hyperpolarized (13)C-succinate imaging of brain cancer.

We describe a novel (13)C enriched precursor molecule, sodium 1-(13)C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized (13)C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized (13)C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized (13)C sodium succinate, contained significant concentrations of the injected substrate, (13)C sodium succinate, together with (13)C maleate and succinate metabolites 1-(13)C-glutamate, 5-(13)C-glutamate, 1-(13)C-glutamine and 5-(13)C-glutamine. The (13)C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized (13)C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in (13)C MR spectral-spatial images.

Epidemiology of blunt head injury victims undergoing ED cranial computed tomographic scanning.

STUDY OBJECTIVE: We sought to describe the epidemiology of emergency department (ED) patients with blunt head injury undergoing cranial computed tomography (CT) scanning for the evaluation of possible traumatic brain injury (TBI). METHODS: Prospective, multicenter, observational study of ED patients undergoing cranial CT after blunt head injury. Patient's date of birth, sex, and race/ethnicity were documented before CT scanning. Individual patients were considered to have "significant" TBI if the official radiographic interpretation at the end of all imaging studies associated with the trauma was consistent with any of a set of predefined diagnoses. The relative prevalence of TBI among various prespecified groups from those undergoing cranial CT scanning was also calculated. RESULTS: Of 13728 patients who were enrolled, 8988 (65%) were men and 1193 (8.7%) had a significant acute TBI. Demographic findings associated with increased risk of TBI, among patients selected for scanning, included the following: age below 10 years (relative risk [RR] = 1.44, 95% confidence interval [CI], 1.19-1.77); age above 65 years (RR = 1.59; 95% CI, 1.40-1.80), and male sex (RR = 1.27; 95% CI, 1.30-1.43). CONCLUSION: Among patients selected for cranial CT scanning after blunt head injury, men, patients younger than 10 years, and those older than 65 years have an increased likelihood of significant TBI.