Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits.

Recent progress in understanding the diversity of midbrain dopamine neurons has highlighted the importance--and the challenges--of defining mammalian neuronal cell types. Although neurons may be best categorized using inclusive criteria spanning biophysical properties, wiring of inputs, wiring of outputs, and activity during behavior, linking all of these measurements to cell types within the intact brains of living mammals has been difficult. Here, using an array of intact-brain circuit interrogation tools, including CLARITY, COLM, optogenetics, viral tracing, and fiber photometry, we explore the diversity of dopamine neurons within the substantia nigra pars compacta (SNc). We identify two parallel nigrostriatal dopamine neuron subpopulations differing in biophysical properties, input wiring, output wiring to dorsomedial striatum (DMS) versus dorsolateral striatum (DLS), and natural activity patterns during free behavior. Our results reveal independently operating nigrostriatal information streams, with implications for understanding the logic of dopaminergic feedback circuits and the diversity of mammalian neuronal cell types.

Multisystem Inflammatory Syndrome in Children - Initial Therapy and Outcomes.

BACKGROUND: The assessment of real-world effectiveness of immunomodulatory medications for multisystem inflammatory syndrome in children (MIS-C) may guide therapy. METHODS: We analyzed surveillance data on inpatients younger than 21 years of age who had MIS-C and were admitted to 1 of 58 U.S. hospitals between March 15 and October 31, 2020. The effectiveness of initial immunomodulatory therapy (day 0, indicating the first day any such therapy for MIS-C was given) with intravenous immune globulin (IVIG) plus glucocorticoids, as compared with IVIG alone, was evaluated with propensity-score matching and inverse probability weighting, with adjustment for baseline MIS-C severity and demographic characteristics. The primary outcome was cardiovascular dysfunction (a composite of left ventricular dysfunction or shock resulting in the use of vasopressors) on or after day 2. Secondary outcomes included the components of the primary outcome, the receipt of adjunctive treatment (glucocorticoids in patients not already receiving glucocorticoids on day 0, a biologic, or a second dose of IVIG) on or after day 1, and persistent or recurrent fever on or after day 2. RESULTS: A total of 518 patients with MIS-C (median age, 8.7 years) received at least one immunomodulatory therapy; 75% had been previously healthy, and 9 died. In the propensity-score-matched analysis, initial treatment with IVIG plus glucocorticoids (103 patients) was associated with a lower risk of cardiovascular dysfunction on or after day 2 than IVIG alone (103 patients) (17% vs. 31%; risk ratio, 0.56; 95% confidence interval [CI], 0.34 to 0.94). The risks of the components of the composite outcome were also lower among those who received IVIG plus glucocorticoids: left ventricular dysfunction occurred in 8% and 17% of the patients, respectively (risk ratio, 0.46; 95% CI, 0.19 to 1.15), and shock resulting in vasopressor use in 13% and 24% (risk ratio, 0.54; 95% CI, 0.29 to 1.00). The use of adjunctive therapy was lower among patients who received IVIG plus glucocorticoids than among those who received IVIG alone (34% vs. 70%; risk ratio, 0.49; 95% CI, 0.36 to 0.65), but the risk of fever was unaffected (31% and 40%, respectively; risk ratio, 0.78; 95% CI, 0.53 to 1.13). The inverse-probability-weighted analysis confirmed the results of the propensity-score-matched analysis. CONCLUSIONS: Among children and adolescents with MIS-C, initial treatment with IVIG plus glucocorticoids was associated with a lower risk of new or persistent cardiovascular dysfunction than IVIG alone. (Funded by the Centers for Disease Control and Prevention.).

Low left ventricular outflow tract velocity time integral predicts normotensive shock in patients with acute pulmonary embolism.

In this study, we found that a low LVOT VTI (<15 cm), a simple bedside point-of-care measurement, predicts normotensive shock in patients with acute intermediate-risk PE.

Shock Index is a Stronger Predictor of Outcomes in Older Compared to Younger Patients.

INTRODUCTION: The shock index (SI) is a known predictor of unfavorable outcomes in trauma. This study seeks to examine and compare the SI values between geriatric patients and younger adults. METHODS: We conducted a retrospective study of the Trauma Quality Improvement Program database from 2017 to 2019. All patients≥ 25 y with injury severity score ≥ 16 were included. Age groups were defined as 25-44 y (group A), 45-64 y (group B), and ≥65 y (group C). SI was calculated for all patients. The primary outcome was mortality and secondary outcomes were need for blood transfusion and need for major surgical intervention (consisting angiography, exploratory laparotomy, and thoracotomy). RESULTS: A total of 244,943 patients were studied. The SI was highest in group A (0.82 ± 0.33) and lowest in group C (0.62 ± 0.30) (P < 0.001). Mortality rate of group C (17%) was significantly higher than group A (9.7%) and B (11.3%) (P < 0.001). In group A, each 0.1 increase in SI was associated with mortality (odds ratio [OR] = 1.079), need for blood transfusion (OR = 1.225) and need for major surgical intervention (OR = 1.347) (P < 0.001 for all). In group C, each 0.1 increase in SI was associated with mortality (OR = 1.126), need for blood transfusion (OR = 1.318), and need for major surgical intervention (OR = 1.648) (P < 0.001 for all). The area under the curve of SI was significantly higher in group C compared to other groups for needing a major surgical intervention and need for blood transfusion (P < 0.05 for both). CONCLUSIONS: These results highlight the significance of the SI as a valuable indicator in geriatric patients with severe trauma. The findings show that SI predicts outcomes in geriatrics more strongly than in younger counterparts.

Early Abnormal Vital Signs Predict Poor Outcomes in Normotensive Patients Following Penetrating Trauma.

INTRODUCTION: Because trauma patients in class II shock (blood loss of 15%-30% of total blood volume) arrive normotensive, this makes the identification of shock and subsequent prognostication of outcomes challenging. Our aim was to identify early predictive factors associated with worse outcomes in normotensive patients following penetrating trauma. We hypothesize that abnormalities in initial vital signs portend worse outcomes in normotensive patients following penetrating trauma. METHODS: A retrospective review was performed from 2006 to 2021 using our trauma database and included trauma patients presenting with penetrating trauma with initial normotensive blood pressures (systolic blood pressure ≥90 mmHg). We compared those with a narrow pulse pressure (NPP ≤25% of systolic blood pressure), tachycardia (heart rate ≥100 beats per minute), and elevated shock index (SI ≥ 0.8) to those without. Outcomes included mortality, intensive care unit admission, and ventilator use. Chi-squared, Mann-Whitney tests, and regression analyses were performed as appropriate. RESULTS: We identified 7618 patients with penetrating injuries and normotension on initial trauma bay assessment. On univariate analysis, NPP, tachycardia, and elevated SI were associated with increases in mortality compared to those without. On multivariable logistic regression, only NPP and tachycardia were independently associated with mortality. Tachycardia and an elevated SI were both independently associated with intensive care unit admission. Only an elevated SI had an independent association with ventilator requirements, while an NPP and tachycardia did not. CONCLUSIONS: Immediate trauma bay NPP and tachycardia are independently associated with mortality and adverse outcomes and may provide an opportunity for improved prognostication in normotensive patients following penetrating trauma.

Enteral nutrition in septic shock: a call for a paradigm shift.

PURPOSE OF REVIEW: The purpose of this review is to identify contemporary evidence evaluating enteral nutrition in patients with septic shock, outline risk factors for enteral feeding intolerance (EFI), describe the conundrum of initiating enteral nutrition in patients with septic shock, appraise current EFI definitions, and identify bedside monitors for guiding enteral nutrition therapy. RECENT FINDINGS: The NUTRIREA-2 and NUTRIREA-3 trial results have better informed the dose of enteral nutrition in critically ill patients with circulatory shock. In both trials, patients with predominant septic shock randomized to receive early standard-dose nutrition had more gastrointestinal complications. Compared to other contemporary RCTs that included patients with circulatory shock, patients in the NUTRIREA-2 and NUTRIREA-3 trials had higher bowel ischemia rates, were sicker, and received full-dose enteral nutrition while receiving high baseline dose of vasopressor. These findings suggest severity of illness, vasopressor dose, and enteral nutrition dose impact outcomes. SUMMARY: The provision of early enteral nutrition preserves gut barrier functions; however, these benefits are counterbalanced by potential complications of introducing luminal nutrients into a hypo-perfused gut, including bowel ischemia. Findings from the NUTRIREA2 and NUTRIREA-3 trials substantiate a 'less is more' enteral nutrition dose strategy during the early acute phase of critical illness. In the absence of bedside tools to guide the initiation and advancement of enteral nutrition in patients with septic shock, the benefit of introducing enteral nutrition on preserving gut barrier function must be weighed against the risk of harm by considering dose of vasopressor, dose of enteral nutrition, and severity of illness.

Updates on the clinical integration of point-of-care ultrasound in pediatric emergency medicine.

PURPOSE OF REVIEW: There is expanding evidence for point-of-care ultrasound (POCUS) use in pediatric emergency medicine - this review highlights the benefits and challenges in the clinical integration of high-yield POCUS applications. Specifically, it will delve into POCUS applications during resuscitations, controversies of Focused Assessment with Sonography for Trauma (FAST) in pediatric trauma, POCUS-guided procedures, and examples of clinical pathways where POCUS can expedite definitive care. RECENT FINDINGS: POCUS can enhance diagnostic accuracy and aid in management of pediatric patients in shock and help identify reversible causes during cardiac arrest. The use of the FAST in pediatric blunt abdominal trauma remains nuanced - its proper use requires an integration with clinical findings and an appreciation of its limitations. POCUS has been shown to enhance safety and efficacy of procedures such as nerve blocks, incision & drainage, and intravenous access. Integrating POCUS into pathways for conditions such as intussusception and testicular torsion expedites downstream care. SUMMARY: POCUS enhances diagnostic efficiency and management in pediatric patients arriving at the ED with undifferentiated shock, cardiac arrest, or trauma. Additionally, POCUS improves procedural success and safety, and is integral to clinical pathways for expediting definitive care for various pediatric emergencies. Future research should continue to focus on the impact of POCUS on patient outcomes, ensuring user competency, and the expansion of POCUS into diverse settings.

ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. METHODS: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h. RESULTS: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients. CONCLUSIONS: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Venous-arterial extracorporeal membrane oxygenation for psittacosis pneumonia complicated with cardiogenic shock: case report and literature review.

INTRODUCTION: Dilated cardiomyopathy (DCM) is characterized by the enlargement of the left ventricle or biventricular, accompanied by myocardial systolic dysfunction. Chlamydia psittacosis (CP) is a zoonotic pathogen, which can cause severe pneumonia, respiratory failure, and acute organ dysfunction. The deterioration of DCM caused by CP infection is extremely rare, and few cases of successful management were reported. CASE PRESENTATION: We reported a 67-year-old male patient with DCM and chronic heart failure. Who was admitted to ICU with severe pneumonia, acute hypoxemic respiratory failure, acute decompensated heart failure, arrhythmia, and cardiogenic shock. Mechanical ventilation (MV) and venous-arterial extracorporeal membrane oxygenation (VA-ECMO) were established for respiratory and circulatory support. Broncho alveolar lavage fluid(BALF)was collected for culture and metagenomics next-generation sequencing (mNGS) test. Repeated mNGS tests indicated the high possibility of CP pneumonia, thereafter, moxifloxacin and doxycycline were prescribed. After targeted antibiotics and organ support treatment, pneumonia, respiratory and circulatory failure were gradually resolved, patient was successfully weaned from MV and VA-ECMO. Finally, the patient was recovered and discharged alive. CONCLUSIONS: Severe respiratory and circulatory failure caused by CP infection in DCM patients is a rare life-threatening clinical condition. Early accurate diagnosis, targeted antibiotic therapy, coupled with extracorporeal life support posed positive impact on the patient's disease course and outcome.

Peripheral Veno-Arterial-Extracorporeal Membrane Oxygenation for Refractory Septic Shock in Children: A Multicenter Review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is utilized as a rescue therapy in the management of pediatric patients with refractory septic shock. Multiple studies support the use of a central cannulation strategy in these patients. This study aimed to assess the survival of and identify mortality risk factors in pediatric patients supported with peripheral veno-arterial (VA) ECMO in the setting of septic shock. METHODS: We retrospectively reviewed and compared clinical characteristics of 40 pediatric patients supported with peripheral VA ECMO for refractory septic shock, at two tertiary care children's hospitals from 2006 to 2020. Our hypothesis was that peripheral VA ECMO is effective in supporting cardiac function and improving tissue oxygenation in most pediatric patients with refractory septic shock. RESULTS: The overall rate of survival to discharge was 52.5%, comparable to previously reported survival for pediatric sepsis on ECMO. With the exclusion of patients with an oncologic process, the survival rate rose to 62.5%. There was a statistically significant difference in mean pump flow rates within 2 hours of initiation of ECMO between survivors and non-survivors (98 mL/kg/min vs 76 mL/kg/min, P = .050). There was no significant difference between pre-ECMO vasoactive inotropic score (VIS) in survivors and non-survivors. A faster decrease in VIS in the first 24 hours was associated with lower mortality. CONCLUSIONS: From this large case series, we conclude that peripheral VA ECMO is a safe and effective modality to support pediatric patients with refractory septic shock, provided there is establishment of high ECMO pump flows in the first few hours after cannulation and improvement in the VIS.

Early Autocalibrated Arterial Waveform Analysis for the Management of Burn Shock-A Cohort Study.

Adequate fluid therapy is crucial for resuscitation after major burns. To adapt this to individual patient demands, standard is adjustment of volume to laboratory parameters and values of enhanced hemodynamic monitoring. To implement calibrated parameters, patients must have reached the intensive care unit (ICU). The aim of this study was, to evaluate the use of an auto-calibrated enhanced hemodynamic monitoring device to improve fluid management before admission to ICU. We used PulsioflexProAqt® (Getinge) during initial treatment and burn shock resuscitation. Analysis was performed regarding time of measurement, volume management, organ dysfunction, and mortality. We conducted a monocentre, prospective cohort study of 20 severely burned patients, >20% total body surface area (TBSA), receiving monitoring immediately after admission. We compared to 57 patients, matched in terms of TBSA, age, sex, and existence of inhalation injury out of a retrospective control group, who received standard care. Hemodynamic measurement with autocalibrated monitoring started significantly earlier: 3.75(2.67-6.0) hours (h) after trauma in the study group versus 13.6(8.1-17.5) h in the control group (P < .001). Study group received less fluid after 6 h: 1.7(1.2-2.2) versus 2.3(1.6-2.8) ml/TBSA%/kg, P = .043 and 12 h: 3.0(2.5-4.0) versus 4.2(3.1-5.0) ml/TBSA%/kg, P = .047. Dosage of norepinephrine was higher after 18 h in the study group: 0.20(0.12-0.3) versus 0.08(0.02-0.18) µg/kg/min, P = .014. The study group showed no adult respiratory distress syndrome versus 21% in the control group, P = .031. There was no difference in other organ failures, organ replacement therapy, and mortality. The use of auto-calibrated enhanced hemodynamic monitoring is a fast and feasible way to guide early fluid therapy after burn trauma. It reduces the time to reach information about patient's volume capacity. Management of fluid application changed to a more restrictive fluid use in the early period of burn shock and led to a reduction of pulmonary complications.

Abnormal obstetric shock index and associated factors among immediate postpartum women following vaginal delivery at a tertiary hospital in southwestern Uganda.

BACKGROUND: Early recognition of haemodynamic instability after birth and prompt interventions are necessary to reduce adverse maternal outcomes due to postpartum haemorrhage. Obstetric shock Index (OSI) has been recommended as a simple, accurate, reliable, and low-cost early diagnostic measure that identifies hemodynamically unstable women. OBJECTIVES: We determined the prevalence of abnormal obstetric shock index and associated factors among women in the immediate postpartum period following vaginal delivery at Mbarara Regional Referral Hospital (MRRH) in southwestern Uganda. METHODS: We conducted a cross-sectional study at the labour suite and postnatal ward of MRRH from January 2022 to April 2022. We systematically sampled women who had delivered vaginally, and measured their blood pressures and pulse rates at 1 h postpartum. We excluded mothers with hypertensive disorders of pregnancy. Sociodemographic, medical and obstetric data were obtained through interviewer-administered questionnaires. The prevalence of abnormal OSI was the proportion of participants with an OSI ≥ 0.9 (calculated as the pulse rate divided by the systolic BP). Logistic regression analysis was used to determine associations between abnormal OSI and independent variables. RESULTS: We enrolled 427 women with a mean age of 25.66 ± 5.30 years. Of these, 83 (19.44%), 95% CI (15.79-23.52) had an abnormal obstetric shock index. Being referred [aPR 1.94, 95% CI (1.31-2.88), p = 0.001], having had antepartum haemorrhage [aPR 2.63, 95% CI (1.26-5.73), p = 0.010] and having a visually estimated blood loss > 200 mls [aPR 1.59, 95% CI (1.08-2.33), p = 0.018] were significantly associated with abnormal OSI. CONCLUSION: Approximately one in every five women who delivered vaginally at MRRH during the study period had an abnormal OSI. We recommend that clinicians have a high index of suspicion for haemodynamic instability among women in the immediate postpartum period. Mothers who are referred in from other facilities, those that get antepartum haemorrhage and those with estimated blood loss > 200mls should be prioritized for close monitoring. It should be noted that the study was not powered to study the factors associated with AOSI and therefore the analysis for factors associated should be considered exploratory.

Performance of Tools and Measures to Predict Fluid Responsiveness in Pediatric Shock and Critical Illness: A Systematic Review and Meta-Analysis.

OBJECTIVES: In this systematic review and meta-analysis we asked: Do predictors of fluid responsiveness in children perform comparably: 1) in the PICU as in non-PICU settings? 2) in shock states compared with nonshock states? Additionally, 3) is there an association between preload responsiveness and clinical response? DATA SOURCES: Ovid Medline, PubMed, and Embase databases were searched from inception through May 2022. STUDY SELECTION: Included studies reported physiological response to IV fluid administration in humans less than 18 years. Only studies reporting an area under the receiver operating characteristic curve (AUROC) were included for descriptive analysis. Only studies for which a se could be estimated were included for meta-analysis. DATA EXTRACTION: Title, abstract, full text screening, and extraction were completed by two authors (S.B.W., J.M.W.). Variables extracted included predictors ("tools") and outcome measures ("reference tests") of fluid responsiveness, demographic, and clinical variables. DATA SYNTHESIS: We identified 62 articles containing 204 AUROCs for 55 tools, primarily describing mechanically ventilated children in an operating room or PICU. Meta-analysis across all tools showed poor predictive performance (AUROC, 0.66; 95% CI, 0.63-0.69), although individual performance varied greatly (range, 0.49-0.87). After controlling for PICU setting and shock state, PICU setting was associated with decreased predictive performance (coefficient, -0.56; p = 0.0007), while shock state was associated with increased performance (0.54; p = 0.0006). Effect of PICU setting and shock state on each tool was not statistically significant but analysis was limited by sample size. The association between preload responsiveness and clinical response was rarely studied but results did not suggest an association. Ultrasound measurements were prone to inherent test review and incorporation biases. CONCLUSIONS: We suggest three opportunities for further research in fluid responsiveness in children: 1) assessing predictive performance of tools during resuscitation in shock states; 2) separating predictive tool from reference test when using ultrasound techniques; and 3) targeting decreasing time in a shock state, rather than just increase in preload.

Resuscitation With Vitamin C, Hydrocortisone, and Thiamin in Children With Septic Shock: A Multicenter Randomized Pilot Study.

OBJECTIVES: Adjunctive therapy with vitamin C, hydrocortisone, and thiamin has been evaluated in adults, but randomized controlled trial (RCT) data in children are lacking. We aimed to test the feasibility of vitamin C, hydrocortisone, and thiamin in PICU patients with septic shock; and to explore whether the intervention is associated with increased survival free of organ dysfunction. DESIGN: Open-label parallel, pilot RCT multicenter study. The primary endpoint was feasibility. Clinical endpoints included survival free of organ dysfunction censored at 28 days and nine secondary outcomes, shock reversal, and two proxy measures of intervention efficacy. SETTING: Six PICUs in Australia and New Zealand. PATIENTS: Children of age between 28 days and 18 years requiring vasoactive drugs for septic shock between August 2019 and March 2021. INTERVENTIONS: Patients were assigned 1:1 to receive 1 mg/kg hydrocortisone every 6 hours (q6h), 30 mg/kg ascorbic acid q6h, and 4 mg/kg thiamin every 12 hours (n = 27), or standard septic shock management (n = 33). MEASUREMENTS AND MAIN RESULTS: Sixty of 77 (78%) eligible patients consented with 91% of approached parents providing consent. The median time from randomization to intervention was 44 (interquartile range [IQR] 29-120) min. Seventy of seventy-seven (28%) patients had received IV steroids before randomization. Median survival alive and free of organ dysfunction was 20.0 (0.0-26.0) days in the intervention and 21.0 (0.0-25.0) days in the standard care group. Median PICU length of stay was 5.3 (2.5-11.3) days in the intervention group versus 6.9 (3.0-11.5) days in the control group. Shock reversal occurred at a median of 35.2 (14.6-101.2) hours in the intervention group versus 47.3 (22.4-106.8) hours in the standard care group (median difference -12 hr; 95% CI, -56.8 to 32.7 hr). CONCLUSIONS: In children requiring vasopressors for septic shock, a protocol comparing adjunctive treatment with high-dose vitamin C, hydrocortisone, and thiamin versus standard care was feasible. These findings assist in making modifications to the trial protocol to enable a better-designed larger RCT.

Effect of decreasing PEEP on hyperinflation and collapse in COVID-19: A computed tomography study.

BACKGROUND: High positive end-expiratory pressure (PEEP>10 cmH2O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH2O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19. METHODS: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH2O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative. RESULTS: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO2:FiO2) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL. CONCLUSION: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse.

Prehospital Administration of Norepinephrine and Epinephrine for Shock after Resuscitation from Cardiac Arrest.

INTRODUCTION: Shock after resuscitation from out-of-hospital cardiac arrest (OHCA) is often treated with vasopressors. We examined whether infusion of epinephrine versus norepinephrine was associated with prehospital rearrest and neurologically favorable survival among OHCA patients. METHODS: This retrospective study included OHCA cases in Seattle, Washington from 2014-2021 who had return of spontaneous circulation (ROSC) followed by vasopressor infusion. Our primary exposure was infusion of epinephrine or norepinephrine. Our primary outcome was prehospital rearrest. Secondary outcomes included survival and neurologically favorable outcome (Cerebral Performance Category score of 1 or 2). We used multivariable logistic regression to test associations between exposures and outcomes adjusting for key covariates. RESULTS: Of 451 OHCA patients with ROSC followed by vasopressor infusion, 253 (56%) received norepinephrine and 198 (44%) received epinephrine infusions. Those who received epinephrine were older (median 66 [interquartile ranges {IQR} 53-79] vs 63 [IQR 47-75] years), but otherwise had similar baseline characteristics. Patients who received epinephrine were twice as likely to rearrest (55% vs 25%). After adjustment, the difference in rearrest rates between epinephrine and norepinephrine persisted (OR 3.28, 95%CI 2.25-5.08), and the odds of pulses at hospital arrival were lower in the epinephrine group (OR 0.52 95%CI 0.32-0.83). After adjustment, there was no difference in neurologically favorable survival, survival to hospital admission, or survival to discharge. CONCLUSION: Patients who received epinephrine infusions after ROSC suffered prehospital rearrest more frequently than those who received norepinephrine. Survival and neurological status at hospital discharge were similar. Future trials should examine the optimal approach to hemodynamic management for post-OHCA shock.

Shock Index as a Predictor of Mortality and Hospital Admission in Prehospital Gastrointestinal Bleeding: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the Shock Index (SI) as a predictive tool for triage of gastrointestinal bleeding (GI) in the prehospital setting, assessing its correlation with mortality, admission rates, and hospital length of stay. METHODS: In this retrospective cohort study, we analyzed data from the ESO Data Collaborative encompassing EMS records from the year 2022, focusing on 1525 patients with a primary GI bleeding diagnosis. The primary measure was the SI, calculated at initial contact and highest recorded prior to ED arrival. Statistical analysis included t-tests, linear regression, and ROC curves, performed using SPSS v29. RESULTS: A significantly higher mean SI was observed in patients who died (mean SI 0.997) compared to survivors (mean SI 0.795), p < 0.001. Admission rates also correlated with higher SI values, p < 0.001. However, SI was not predictive of the hospital length of stay. ROC analysis for mortality prediction yielded an AUC of 0.656 for the initial SI and 0.739 for the highest SI. The standard SI cutoff of 0.9 predicted mortality with a sensitivity of 74.14% and specificity of 55.35% for the highest SI. CONCLUSION: The SI is a valuable predictive tool for mortality among prehospital patients with GI bleeding. Its application may improve the triage process, potentially influencing transport decisions and initial hospital care. Despite its predictive capability for mortality, the SI should be supplemented with other clinical assessments to make comprehensive prehospital care decisions. Further research into SI as part of a comprehensive assessment which includes end-title CO2, mentation, and heaviness of bleeding.

Prehospital Shock Index Multiplied by the Alert/Verbal/Painful/Unresponsive Score as a Predictor of Clinical Outcomes in Traumatic Injury.

OBJECTIVE: Various prediction scores have been developed to predict mortality in trauma patients, such as the shock index (SI), modified SI (mSI), age-adjusted SI (aSI), and the shock index (SI) multiplied by the alert/verbal/painful/unresponsive (AVPU) score (SIAVPU). The SIAVPU is a novel scoring system but its prediction accuracy for trauma outcomes remains in need of further validation. Therefore, we investigated the accuracy of four scoring systems, including SI, mSI, aSI, and SIAVPU, in predicting mortality, admission to the intensive care unit (ICU), and prolonged hospital length of stay ≥ 30 days (LOS). METHODS: This retrospective multicenter study used data from the Tzu Chi Hospital trauma database. The area under the receiver operating characteristic curve (AUROC) was determined for each outcome to assess their discrimination capabilities and comparing by Delong's test. Subgroup analyses were conducted to investigate the prediction accuracy of the SIAVPU in different patient populations. RESULTS: In total, 5355 patients were included in the analysis. The median of SIAVPU were significantly higher among patients at those with major injury (1.47 vs 0.63), those admitted to the ICU (0.73 vs 0.62), those with prolonged hospital LOS≥ 30 days (0.83 vs 0.64), and those with mortality (1.08 vs 0.64). The AUROC of the SIAVPU was significantly higher than that of the SI, mSI, and aSI for 24-h mortality (AUROC: 0.845 vs 0.533, 0.540, and 0.678), 3-day mortality (AUROC: 0.803 vs 0.513, 0.524, and 0.688), 7-day mortality (AUROC: 0.755 vs 0.494, 0.505, and 0.648), in-hospital mortality (AUROC: 0.722 vs 0.510, 0.524, and 0.667), ICU admission (AUROC: 0.635 vs 0.547, 0.551, and 0.563). At the optimal cutoff value of 0.9, the SIAVPU had an accuracy of 82.2% for predicting 24-h mortality, 82.8% for predicting 3-day mortality, of 82.8% for predicting 7-day mortality, of 82.5% for predicting in-hospital mortality, of 73.9% for predicting Intensive Care Unit (ICU) admission, and of 81.7% for predicting prolonged hospital LOS ≥30 days. CONCLUSIONS: Our results reveal that SIAVPU has better accuracy than the SI, mSI, and aSI for predicting 24-h, 3-day, 7-day, and in-hospital mortality; ICU admission; and prolonged hospital LOS ≥30 days among patients with traumatic injury.

Two cases of systemic capillary leak syndrome associated with COVID-19 in Japan.

Systemic Capillary Leak Syndrome (SCLS) is a rare disease that causes severe distributive shock provoked by infection or vaccination. SCLS is clinically diagnosed by a triad of distributive shock, paradoxical hemoconcentration, and hypoalbuminemia. SCLS associated with coronavirus disease (COVID-19) in adults has not been reported yet in Japan. Case 1: A 61-year-old woman with fever, sore throat, headache, and muscle pain was admitted to our emergency department with suspected COVID-19. She had been diagnosed with SCLS 3 years earlier. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen and polymerase chain reaction (PCR) tests were negative at admission. She went into shock in the emergency department and was treated for septic shock. The following day, the SARS-CoV-2 PCR test was positive. She did not respond to fluid resuscitation and catecholamine and finally died. Case 2: A 58-year-old man was admitted to our hospital for de-saturation due to COVID-19. He got into shock on day 3. SCLS was suspected, and 5 g of intravenous immunoglobulin and 5% albumin were administered for sepsis treatment. He responded to the aggressive fluid therapy within 48 h and was finally discharged. COVID-19 can trigger SCLS, and early recognition of SCLS is crucial for survival. Primary care physicians should consider SCLS when they observe distributive shock and paradoxical hemoconcentration deviations from the natural course of COVID-19.

Centiles for the shock index among injured children in the prehospital setting.

OBJECTIVE: The shock index (SI), the ratio of heart rate to systolic blood pressure, is a clinical tool for assessing injury severity. Age-adjusted SI models may improve predictive value for injured children in the out-of-hospital setting. We sought to characterize the proportion of children in the prehospital setting with an abnormal SI using established criteria, describe the age-based distribution of SI among injured children, and determine prehospital interventions by SI. METHODS: We performed a multi-agency retrospective cross-sectional study of children (<18 years) in the prehospital setting with a scene encounter for suspected trauma and transported to the hospital between 2018 and 2022 using the National Emergency Medical Services (EMS) Information System datasets. Our exposure of interest was the first calculated SI. We identified the proportion of children with an abnormal SI when using the SI, pediatric age-adjusted (SIPA); and the pediatric SI (PSI) criteria. We developed and internally validated an age-based distributional model for the SI using generalized additive models for location, scale, and shape to describe the age-based distribution of the SI as a centile or Z-score. We evaluated EMS interventions (basic airway interventions, advanced airway interventions, cardiac interventions, vascular access, intravenous fluids, and vasopressor use) in relation to both the SIPA, PSI, and distributional SI values. RESULTS: We analyzed 1,007,863 pediatric EMS trauma encounters (55.0% male, median age 13 years [IQR, 8-16 years]). The most common dispatch complaint was for traffic/transport related injury (32.9%). When using the PSI and SIPA, 13.1% and 16.3% were classified as having an abnormal SI, respectively. There were broad differences in the percentage of encounters classified as having an abnormal SI across the age range, varying from 5.1 to 22.8% for SIPA and 3.7-20.1% for PSI. The SIPA values ranged from the 75th to 95th centiles, while the PSI corresponded to an SI greater than the 90th centile, except in older children. The centile distribution for SI declined during early childhood and stabilized during adolescence and demonstrated a difference of <0.1% at cutoff values. An abnormal PSI, SIPA and higher SI centiles (>90th centile and >95th centiles) were associated with interventions related to basic and advanced airway management, cardiac procedures, vascular access, and provision of intravenous fluids occurred with greater frequency at higher SI centiles. Some procedures, including airway management and vascular access, had a smaller peak at lower (<10th) centiles. DISCUSSION: We describe the empiric distribution of the pediatric SI across the age range, which may overcome limitations of extant criteria in identifying patients with shock in the prehospital setting. Both high and low SI values were associated with important, potentially lifesaving EMS interventions. Future work may allow for more precise identification of children with significant injury using cutpoint analysis paired to outcome-based criteria. These may additionally be combined with other physiologic and mechanistic criteria to assist in triage decisions.