Pulse Oximeter Plethysmograph Variation During Hemorrhage in Beta-Blocker-Treated Swine.

BACKGROUND: Beta-blockers blunt the stress response to hemorrhage. Our aim was to investigate the feasibility of noninvasive pulse oximeter plethysmographic waveform variation (PoPV) for predicting blood volume loss in an esmolol-treated swine hemorrhagic shock model. MATERIALS AND METHODS: Controlled hemorrhage was induced in eight male domestic pigs. In four pigs, a total of 15% and 30% blood volume was drawn step-by-step over 10 min in each step (controlled hemorrhage-only pigs). In the other four pigs, the heart rate (HR) was reduced and maintained by 30% from baseline by esmolol infusion before controlled hemorrhage (esmolol-treated pigs). Diagnostic abilities of HR, pulse pressure variation (PPV), PoPV, and mean arterial pressure for 15% and 30% blood volume loss were determined by the area under the receiver operating characteristic curve (AUC). RESULTS: PoPV was well correlated with PPV in controlled hemorrhage-only pigs (r = 0.717) and esmolol-treated pigs (r = 0.532). In controlled hemorrhage-only pigs, HR (AUC = 0.841 and 0.864), PPV (0.878 and 0.843), and PoPV (0.779 and 0.793) accurately predicted 15% and 30% of blood volume loss. In esmolol-treated pigs, the diagnostic ability of HR was decreased (AUC = 0.766 and 0.733). However, diagnostic abilities of PPV (0.848 and 0.804) and PoPV (0.808 and 0.842) were not deteriorated. CONCLUSIONS: The diagnostic ability of HR for blood volume loss was blunted by esmolol. However, those of PPV and PoPV were not altered. PoPV may be considered to be a useful noninvasive tool to predict blood volume loss in injured patients taking beta-blockers.

Copeptin with high-sensitivity troponin at presentation is not inferior to serial troponin measurements for ruling out acute myocardial infarction.

OBJECTIVE: We aimed to compare the multi-marker strategy (copeptin and high-sensitivity cardiac troponin I [hs-cTnI]) with serial hs-cTnI measurements to rule out acute myocardial infarction (AMI) in patients with chest pain. METHODS: This prospective observational study was performed in a single emergency department. To test the non-inferiority margin of 4% in terms of negative predictive value (NPV) between the multi-marker strategy (0 hour) and serial hs-cTnI measurements (0 and 2 hours), 262 participants were required. Samples for copeptin and hs-cTnI assays were collected at presentation (0 hour) and after 2 hours. The measured biomarkers were considered abnormal when hs-cTnI was >26.2 ng/L and when copeptin was >10 pmol/L. RESULTS: AMI was diagnosed in 28 patients (10.7%). The NPV of the multi-marker strategy was 100% (160/160; 95% confidence interval [CI], 97.7% to 100%), which was not inferior to that of serial hs-cTnI measurements (201/201; 100%; 95% CI, 98.2% to 100%). The sensitivity, specificity, and positive predictive value of the multi-marker strategy were 100% (95% CI, 87.7% to 100%), 68.1% (95% CI, 61.7% to 74.0%), and 27.2% (95% CI, 18.9% to 36.8%), respectively. The sensitivity, specificity, and positive predictive value of serial hs-cTnI measurements were 100% (95% CI, 87.7% to 100%), 85.5% (95% CI, 80.4% to 89.8%), and 45.2% (95% CI, 32.5% to 58.3%), respectively. CONCLUSION: The multi-marker strategy (copeptin and hs-cTnI measurement) was not inferior to serial hs-cTnI measurements in terms of NPV for AMI diagnosis, with a sensitivity and NPV of 100%. Copeptin may help in the early rule-out of AMI in patients with chest pain.

Duty cycle of 33% increases cardiac output during cardiopulmonary resuscitation.

BACKGROUND: The aim of this study was to investigate whether 33% duty cycle increases end-tidal carbon dioxide (ETCO2) level, a surrogate measurement for cardiac output during cardiopulmonary resuscitation (CPR), compared with 50% duty cycle. METHODS: Six pigs were randomly assigned to the DC33 or DC50 group. After 3 min of induced ventricular fibrillation (VF), CPR was performed for 5 min with 33% duty cycle (DC33 group) or with 50% duty cycle (DC50 group) (phase I). Defibrillation was delivered until return of spontaneous circulation (ROSC) thereafter. After 30 min of stabilization, the animals were re-assigned to the opposite groups. VF was induced again, and CPR was performed (phase II). The primary outcome was ETCO2 during CPR, and the secondary outcomes were coronary perfusion pressure (CPP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and right atrial pressure (RAP). RESULTS: Mean ETCO2 was higher in the DC33 group compared with the DC50 group (22.5 mmHg vs 21.5 mmHg, P = 0.018). In a linear mixed model, 33% duty cycle increased ETCO2 by 1.0 mmHg compared with 50% duty cycle (P < 0.001). ETCO2 increased over time in the DC33 group [0.6 mmHg/min] while ETCO2 decreased in the DC50 group [-0.6 mmHg/min] (P < 0.001). Duty cycle of 33% increased SAP (6.0 mmHg, P < 0.001), DAP (8.9 mmHg, P < 0.001) RAP (2.6 mmHg, P < 0.001) and CPP (4.7 mmHg, P < 0.001) compared with the duty cycle of 50%. CONCLUSION: Duty cycle of 33% increased ETCO2, a surrogate measurement for cardiac output during CPR, compared with duty cycle of 50%. Moreover, ETCO2 increased over time during CPR with 33% duty cycle while ETCO2 decreased with 50% duty cycle.

Emergency physician-based intensive care unit for critically ill patients visiting emergency department.

BACKGROUND: To provide a prompt and optimal intensive care to critically ill patients visiting our emergency department (ED), we set up and ran a specific type of emergency intensive care unit (EICU) managed by emergency physician (EP) intensivists. We investigated whether this EICU reduced the time interval from ED arrival to ICU transfer (ED-ICU interval) without altering mortality. METHODS: This was a retrospective study conducted in a tertiary referral hospital. We collected data from ED patients who were admitted to the EICU (EICU group) and other ICUs including medical, surgical, and cardiopulmonary ICUs (other ICUs group), from August 2014 to July 2017. We compared these two groups with respect to demographic findings, including the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, ED-ICU interval, ICU mortality, and hospital mortality. RESULTS: Among the 3440 critically ill patients who visited ED, 1815 (52.8%) were admitted to the EICU during the study period. The ED-ICU interval for the EICU group was significantly shorter than that for the other ICUs group by 27.5% (5.0 ±â€¯4.9 vs. 6.9 ±â€¯5.4 h, p < 0.001). In multivariable analysis, the ICU mortality (odds ratio = 1.062, 95% confidence interval 0.862-1.308, p = 0.571) and hospital mortality (odds ratio = 1.093, 95% confidence interval 0.892-1.338, p = 0.391) of the EICU group were not inferior to those of the other ICUs group. CONCLUSIONS: The EICU run by EP intensivists reduced the time interval from ED arrival to ICU transfer without altering hospital mortality.

Delayed endoscopy is associated with increased mortality in upper gastrointestinal hemorrhage.

OBJECTIVES: To determine the association between delayed (>24 h) endoscopy and hospital mortality in patients with upper gastrointestinal hemorrhage (UGIH). METHODS: We retrospectively analyzed all adult patients with UGIH who underwent endoscopy in a single emergency room for 2 years. The primary exposure was defined as >24 h from the ED visit to the first endoscopy. The primary outcome was defined as all cause hospital mortality. Secondary outcomes were intensive care unit admission rate, ED length of stay, and hospital length of stay. RESULTS: Among 1101 patients enrolled, 898 received endoscopy within 24 h (early group) and 203 received endoscopy after 24 h (delayed group). The hospital mortality of early and delayed group was 2.8% and 6.4%, respectively (unadjusted relative risk [RR] 2.30: 95% CI, 1.20-4.42, p = 0.012). This was significant after adjusting covariates including AIMS65 and Glasgow-Blatchford score (adjusted RR 2.23: 95% CI, 1.18-4.20, p = 0.013). Intensive care unit admission rate was not different between two groups. ED and hospital length of stay were significantly longer in delayed group. CONCLUSIONS: Endoscopy performed after 24 h was associated with increased hospital mortality in UGIH. Patients in the delayed group stayed longer in the ED and in the hospital.

Relative tachycardia is associated with poor outcomes in post-cardiac arrest patients regardless of therapeutic hypothermia.

BACKGROUND: To investigate whether the relationship between heart rate and neurological outcome is independent of therapeutic hypothermia (TH) and whether heart rate is related to hemodynamic instability post-cardiac arrest. METHODS: Retrospective review of an out-of-hospital cardiac arrest registry was performed. The primary exposure was heart rate quartiles at 24 h post-cardiac arrest. The primary outcome was a poor neurological outcome, which was defined as having a cerebral performance category (CPC) of 3-5 at 28 days. Secondary outcomes were mean blood pressure and serum lactate at 24 h and Sequential Organ Failure Assessment (SOFA) scores at admission. RESULTS: In total, 155 patients were enrolled. The proportion of patients with a poor CPC was significantly greater in higher heart rate quartiles; similar results were observed in patients who did and did not undergo TH. Serum lactate levels at 24 h were significantly higher in the 3rd and 4th quartile groups than in the 1st quartile group. Additionally, SOFA scores were significantly higher in the 4th quartile group than in the 1st and 3rd quartile groups. CONCLUSIONS: Relative tachycardia is associated with poor neurological outcomes in post-cardiac arrest patients, independent of TH, and with higher serum lactate levels and admission SOFA scores.

Validation of non-invasive brain temperature estimation models during swine therapeutic hypothermia.

OBJECTIVES: This paper introduces a mathematical model that can estimate deep brain temperature during therapeutic hypothermia (TH) based on a double sensor method (DSM). Although the cerebral temperature is more important than the non-cerebral core temperature during TH, pulmonary artery (PA), rectal, and esophageal measurements (i.e. the typical core temperature measurement locations) have all been used for target temperature management. This is because there is no safe means of measuring the exact brain temperature. APPROACH: We applied a double sensor thermometer to the subject's forehead to measure the cerebral temperature non-invasively. Invasive and non-invasive brain temperature readings were acquired for 11 pigs, seven of which were used to develop an optimal model using jackknife resampling and four of which were used to test the model. MAIN RESULTS: The logit model exhibited the best performance of 0.134 °C root mean square error and a 0.993 Lin's concordance correlation coefficient (CCC). Each test dataset had acceptable results in that each 95% limit of agreement was within the range of clinical acceptance of [-0.5 °C, 0.5 °C]. Three of the four datasets yielded an 'almost perfect' score for Lin's CCC. SIGNIFICANCE: Only a small number of studies have compared invasively and non-invasively measured brain temperatures, while most previous studies have concentrated on comparison with the core temperature. Furthermore, the possibility of measuring the exact brain temperature safely during TH using a DSM is shown in this work.

Association between the simultaneous decrease in the levels of soluble vascular cell adhesion molecule-1 and S100 protein and good neurological outcomes in cardiac arrest survivors.

OBJECTIVE: This study aimed to determine whether simultaneous decreases in the serum levels of cell adhesion molecules (intracellular cell adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin) and S100 proteins within the first 24 hours after the return of spontaneous circulation were associated with good neurological outcomes in cardiac arrest survivors. METHODS: This retrospective observational study was based on prospectively collected data from a single emergency intensive care unit (ICU). Twenty-nine out-of-hospital cardiac arrest survivors who were admitted to the ICU for post-resuscitation care were enrolled. Blood samples were collected at 0 and 24 hours after ICU admission. According to the 6-month cerebral performance category (CPC) scale, the patients were divided into good (CPC 1 and 2, n=12) and poor (CPC 3 to 5, n=17) outcome groups. RESULTS: No difference was observed between the two groups in terms of the serum levels of ICAM-1, VCAM-1, E-selectin, and S100 at 0 and 24 hours. A simultaneous decrease in the serum levels of VCAM-1 and S100 as well as E-selectin and S100 was associated with good neurological outcomes. When other variables were adjusted, a simultaneous decrease in the serum levels of VCAM-1 and S100 was independently associated with good neurological outcomes (odds ratio, 9.285; 95% confidence interval, 1.073 to 80.318; P=0.043). CONCLUSION: A simultaneous decrease in the serum levels of soluble VCAM-1 and S100 within the first 24 hours after the return of spontaneous circulation was associated with a good neurological outcome in out-of-hospital cardiac arrest survivors.

Prediction of neurological outcomes following the return of spontaneous circulation in patients with out-of-hospital cardiac arrest: Retrospective fast-and-frugal tree analysis.

AIM: Although various quantitative methods have been developed for predicting neurological prognosis in patients with out-of-hospital cardiac arrest (OHCA), they are too complex for use in clinical practice. We aimed to develop a simple decision rule for predicting neurological outcomes following the return of spontaneous circulation (ROSC) in patients with OHCA using fast-and-frugal tree (FFT) analysis. METHODS: We performed a retrospective analysis of prospectively collected data archived in a multi-centre registry. Good neurological outcomes were defined as cerebral performance category (CPC) values of 1 or 2 at 28-day. Variables used for FFT analysis included age, sex, witnessed cardiac arrest, bystander cardiopulmonary resuscitation, initial shockable rhythm, prehospital defibrillation, prehospital ROSC, no flow time, low flow time, cause of arrest (cardiac or non-cardiac), pupillary light reflex, and Glasgow Coma Scale score after ROSC. RESULTS: Among the 456 patients enrolled, 86 (18.9%) experienced good neurological outcomes. Prehospital ROSC (true = good), prompt or sluggish light reflex response after ROSC (true = good), and presumed cardiac cause (true = good, false = poor) were selected as nodes for the decision tree. Sensitivity, specificity, positive predictive value, and negative predictive value of the decision tree for predicting good neurological outcomes were 100% (42/42), 64.0% (119/186), 38.5% (42/109), and 100% (119/119) in the training set and 95.5% (42/44), 57.6% (106/184), 35.0% (42/120), and 98.1% (106/108) in the test set, respectively. CONCLUSION: A simple decision rule developed via FFT analysis can aid clinicians in predicting neurological outcomes following ROSC in patients with OHCA.

Lower serum kallistatin level is associated with 28-day mortality in patients with septic shock.

PURPOSE: Investigation for whether serum levels of kallistatin, vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are associated with outcomes in patients with septic shock MATERIAL AND METHODS: Biomarker levels were measured using blood samples from patients with septic shock at admission, 24 h, and 72 h and from healthy volunteers. The primary outcome was 28-day mortality. RESULTS: Fifty-eight survivors, fourteen non-survivors, and six healthy volunteers were enrolled. Serum kallistatin level was lower and serum VCAM-1 and E-selectin levels were higher in patients at admission compared with healthy volunteers. Serum kallistatin levels were higher in survivors compared with non-survivors at all time points (4.4 µg/mL [2.9-6.1] vs. 2.5 µg/mL [2.1-5.0], P = 0.019 at admission; 4.3 µg/mL [3.3-5.2] vs. 3.2 µg/mL [2.2-3.8], P = 0.004 at 24 h; 3.1 µg/mL [2.5-4.2] vs. 2.3 µg/mL [1.7-3.1], P = 0.012 at 72 h), while VCAM-1 and E-selectin levels showed no difference. In the multivariable analysis, serum kallistatin level at 24 h was independently associated with 28-day mortality (OR, 0.29; 95% CI, 0.08-0.69, P = 0.024). CONCLUSIONS: Lower serum kallistatin level at 24 h was independently associated with 28-day mortality in patients with septic shock.

End-tidal CO2-guided automated robot CPR system in the pig. Preliminary communication.

BACKGROUND: Our aim was to compare the efficacy of the end-tidal CO2-guided automated robot CPR (robot CPR) system with manual CPR and mechanical device CPR. METHODS: We developed the algorithm of the robot CPR system which automatically finds the optimal compression position under the guidance of end-tidal CO2 feedback in swine models of cardiac arrest. Then, 18 pigs after 11 min of cardiac arrest were randomly assigned to one of three groups, robot CPR, LUCAS CPR, and manual CPR groups (n = 6 each group). Return of spontaneous circulation (ROSC) and Neurological Deficit Score 48 h after ROSC were compared. RESULTS: A ROSC was achieved in 5 pigs, 4 pigs, and 3 pigs in the robot CPR, LUCAS CPR, and manual CPR groups, respectively (p = 0.47). Robot CPR showed a significant difference in Neurological Deficit Score 48 h after ROSC compared to manual CPR, whereas LUCAS CPR showed no significant difference over manual CPR. (p = 0.01; Robot versus Manual adjusted p = 0.04, Robot versus LUCAS adjusted p = 0.07, Manual versus LUCAS adjusted p = 1.00). CONCLUSIONS: The end-tidal CO2-guided automated robot CPR system did not significantly improve ROSC rate in a swine model of cardiac arrest. However, robot CPR showed significant improvement of Neurological Deficit Score 48 h after ROSC compared to Manual CPR while LUCAS CPR showed no significant improvement compared to Manual CPR.

Prognostic performance of Emergency Severity Index (ESI) combined with qSOFA score.

OBJECTIVE: We conducted this study to investigate whether ESI combined with qSOFA score (ESI+qSOFA) predicts hospital outcome better than ESI alone in the emergency department (ED). METHODS: This was a retrospective study for patients aged over 15years who visited an ED of a tertiary referral hospital from January 1st, 2015 to December 31st, 2015. We calculated and compared predictive performances of ESI alone and ESI+qSOFA for prespecified outcomes. The primary outcome was hospital mortality, and the secondary outcome was composite outcome of in-hospital mortality and ICU admission. We calculated in-hospital mortality rates by positive qSOFA in each subgroup divided according to ESI levels (1, 2, 3, 4+5). RESULTS: 43,748 patients were enrolled. The area under receiver-operating characteristics curves were higher in ESI+qSOFA than in ESI alone for both mortality and composite outcome (0.786 vs. 0.777, P<.001 for mortality; 0.778 vs. 0.774, P<.001 for composite outcome). In each subgroup divided by ESI levels, patients with positive qSOFA had significantly higher in-hospital mortality rate compared to those with negative qSOFA (20.4% vs. 14.7%, P=.117 in ESI level 1 subgroup; 11.3% vs. 2.7%, P=.001 in ESI level 2 subgroup; 2.3% vs. 0.4%, P<.001 in ESI level 3 subgroup; 0.0% vs. 0.0% in ESI level 4 or 5 subgroup). CONCLUSION: The prognostic performance of ESI+qSOFA for in-hospital mortality was significantly higher than that of ESI alone. Within each subgroup, patients with positive qSOFA had higher in-hospital mortality compared to those with negative qSOFA.