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.

Acupuncture-Induced Hemothorax with Hypovolemic Shock: A Case Report.

This report describes a very rare but life-threatening complication that occurred in a 43-year-old woman after an acupuncture (AC) for lumbago. The patient presented to the emergency department displaying symptoms indicative of shock. Physical examination revealed the absence of breath sounds on the right thoracic side, further investigations indicated the presence of a hemothorax. Emergency surgery was performed to evacuate the hemothorax and control bleeding from two intercostal veins. Although AC is often considered a gentle form of medicine, it is important to recognize that it can occasionally result in severe complications, especially when acupoints are used on the thorax.

Treatment of refractory shock with vitamin B12 : A narrative review.

High-dose vitamin B12 is a potential treatment for patients with vasodilatory shock that is refractory to other therapies. Vasodilatory shock is characterized by low blood pressure and low systemic vascular resistance. Nitric oxide and hydrogen sulfide, two potential targets of high-dose vitamin B12 given as hydroxocobalamin, facilitate this syndrome. This review explores the relationship between high-dose vitamin B12 and hemodynamic outcomes in adults with vasodilatory shock and provides an update on the literature since a 2019 review on this topic. A literature search of studies published in the past 5 years was conducted in the CINAHL, PubMed, Cochrane, and EMBASE databases in May 2023. After assessing for eligibility, eight studies met this review's inclusion criteria. Seven of the eight studies reported decreased vasopressor requirements for part or all of the study samples after receiving a hydroxocobalamin infusion. However, not all patients responded to hydroxocobalamin. These findings are limited by patient selection and differences in the timing of vasopressor requirement and blood pressure outcome assessments. The current evidence is promising as to whether vitamin B12 , given as a hydroxocobalamin infusion, may improve hemodynamic outcomes in vasodilatory shock, but the evidence is of low quality. The use of hydroxocobalamin to treat refractory, vasodilatory shock remains investigative. Larger randomized controlled trials are required to elucidate the role of vitamin B12 in treating refractory, vasodilatory shock, including in conjunction with other alternative therapies such as methylene blue and corticosteroids.

Therapeutic Effects of Shenfu Injection in Shock.

Shock is the clinical manifestation of acute circulatory failure, which results in inadequate utilization of cellular oxygen. It is a common condition with high mortality rates in intensive care units. The intravenous administration of Shenfu Injection (SFI) may attenuate inflammation, regulate hemodynamics and oxygen metabolism; inhibit ischemia-reperfusion responses; and have adaptogenic and antiapoptotic effects. In this review, we have discussed the clinical applications and antishock pharmacological effects of SFI. Further in-depth and large-scale multicenter clinical studies are warranted to determine the therapeutic effects of SFI on shock.

Raise vigilance against refractory distributive shock due to severe wet beriberi.

Differentiating the type and cause of shock is crucial for intensive care. The rapid aggravation of lactic acidosis in patients often indicates a severe impairment of oxygen uptake in tissues. Herein, we presented a rare case of refractory distributive shock with severe wet beriberi. A 40-year-old male was admitted to the emergency department (ED) with recurrent chest tightness and lower extremity edema. The condition of the patient continued to deteriorate after symptomatic treatments. After several turnovers, the medical history of the patient was requested again and finally obtained. Our emergency management team hypothesized that the thiamine-deficient diet caused an aerobic metabolism disorder in the patient. Overall, we aimed to alert clinicians to unusual causes of distributive shock and further discussed the application of thiamine supplementary therapy in critical care.

Evaluation of Venous-to-Arterial Carbon Dioxide Tension Difference as a Complementary Parameter During Pediatric Septic Shock Resuscitation: A Prospective Observational Study.

OBJECTIVES: The aim of this study was to evaluate the venous-to-arterial carbon dioxide tension difference during early resuscitation in pediatric septic shock. METHODS: A prospective observational study was conducted in the pediatric intensive care unit of a tertiary care teaching. Children having septic shock aged from 3 to 60 months were studied within the first 24 hours of admission. Central venous and peripheral arterial blood samples for blood gases analysis at time of central venous catheter insertion and after 6 hours were obtained. Central venous carbon dioxide pressure, arterial carbon dioxide pressure, and their difference (delta Pco2) were recorded. Patients were categorized, accordingly to delta Pco2 after 6 hours of resuscitation, into high delta Pco2 group (≥6 mm Hg) and low delta Pco2 group (<6 mm Hg). RESULTS: Oxygen extraction ratio at 6 hours of resuscitation was significantly lower among the low delta Pco2 group. Arterial lactate showed marked improvement in the low delta Pco2 group to be less than 2 mmol/L at 12 hours of resuscitation. Low delta Pco2 group showed significant higher shock reversal with shorter shock reversal time. Mortality was significantly lower among low delta Pco2 group with shorter pediatric intensive care unit stay. CONCLUSIONS: Delta Pco2 after 6 hours of resuscitation of <6 mm Hg indicates normalization of tissue perfusion during pediatric septic shock management. It could be used as a complementary tool to guide the resuscitation in the early phase of pediatric septic shock.

Alternative shock index cutoffs for pediatric patients outperform the Shock Index Pediatric Age-adjusted (SIPA) on strength of association with adverse outcomes in pediatric trauma patients.

BACKGROUND: The shock index is a tool for evaluating critically ill patients that is defined as the ratio of their heart rate divided by systolic blood pressure. The SI is associated with outcomes in adult trauma patients. The Shock Index Pediatric Age-adjusted was developed as a pediatric-specific tool to account for the physiologic differences of children of varying ages. There is growing interest in Shock Index Pediatric Age-adjusted, which is associated with adverse outcomes in pediatric trauma. We hypothesized that alternative shock index cutoffs based on the Advanced Trauma Life Support or the Pediatric Advanced Life Support vital sign reference ranges would outperform Shock Index Pediatric Age-adjusted. METHODS: We analyzed a retrospective cohort of pediatric trauma patients (age 1 to 16 years old) in the American College of Surgeons Trauma Quality Programs Participant Use File from 2010 to 2018. The primary outcome measure was in-hospital mortality. The Shock Index Pediatric Age-adjusted was compared to an Advanced Trauma Life Support-based and a Pediatric Advanced Life Support-based shock index cutoff system. Our findings were subsequently confirmed with a separate, internal validation data set. RESULTS: A total of 598,830 Trauma Quality Programs Participant Use File patients were included, 0.9% (n = 5,471) of whom died. For mortality, the Advanced Trauma Life Support-based system yielded the highest positive predictive value (15.8%; 95% confidence interval 15.0%-16.7%) compared with the Pediatric Advanced Life Support-based system (4.3%; 95% confidence interval 4.1%-4.5%). Both the Advanced Trauma Life Support-based and Pediatric Advanced Life Support-based systems achieved higher positive predictive values compared to Shock Index Pediatric Age-adjusted (2.6%; 95% confidence interval 2.5%-2.7%). The negative predictive values were not clinically different. Our findings were validated using a separate internal trauma database, in which the positive predictive value for mortality of the Advanced Trauma Life Support-based system was significantly higher than Shock Index Pediatric Age-adjusted (18.2% [95% confidence interval: 8.2%-32.7%] vs 2.9% [95% confidence interval: 1.6%-5.0%], P < .05). CONCLUSION: Advanced Trauma Life Support and Pediatric Advanced Life Support-based shock index cutoffs achieved higher positive predictive values and similar negative predictive values compared to Shock Index Pediatric Age-adjusted for adverse outcomes in pediatric trauma.

Refractory Shock from Amlodipine Overdose Overcomed with Hyperinsulinemia.

Intoxication from calcium channel blockers exhibits almost 50% mortality rates. Amlodipine is a long-acting dihydropyridine and inappropriate dosage poses a great threat for profound vasodilation, hypotension, and refractory vasopressor-resistant shock. A 72-year-old woman with unremarkable medical history presented to the emergency department due to amlodipine overdose after a suicide attempt attributed to COVID-19 pandemic severe anxiety disorder. Vital signs at presentation: heart rate 82 beats/ min, arterial pressure 72/55 mmHg, and oxygen saturation 98%. Resuscitation was initiated with intravenous infusion of normal saline 0,9%, noradrenaline, and calcium chloride, while activated charcoal was orally administrated; however, blood pressure remained at 70/45 mmHg. Abruptly, she experienced acute pulmonary edema and was finally intubated. We commenced high-dose insulin infusion with Dextrose 10% infusion to maintain euglycemic hyperinsulinemia. Hemodynamic improvement occurred after 30 min, systolic blood pressure raised to 95 mmHg, and decongestion was achieved with intravenous furosemide. Insulin effect was dose-dependent and patient's hemodynamic status improved after insulin uptitration. Eight days later, the patient was weaned from the mechanical ventilation and she was successfully discharged after 14 days. High-dose intravenous infusion of insulin up to 10 units/kg per hour appears as an inotropic agent possibly through alterations in myocardial metabolism of fatty acids and augmentation of insulin secretion and uptake. This regimen possibly exhibits additional vasotropic properties. We conclude that euglycemic hyperinsulinemia is a potentially advantageous treatment in CCB toxicity.

Risk Factors of Coronavirus Disease 2019-Related Mortality and Optimal Treatment Regimens: A Retrospective Study.

BACKGROUND Coronavirus disease 2019 (COVID-19) is spreading rapidly worldwide, and scientists are trying to find a way to overcome the disease. We explored the risk factors that influence patient outcomes, including treatment regimens, which can provide a reference for further treatment. MATERIAL AND METHODS A retrospective cohort study analysis was performed using data from 97 patients with COVID-19 who visited Wuhan Union Hospital from February 2020 to March 2020. We collected data on demographics, comorbidities, clinical manifestations, laboratory tests, treatment methods, outcomes, and complications. Patients were divided into a recovered group and a deceased group. We compared the differences between the 2 groups and analyzed risk factors influencing the treatment effect. RESULTS Seventy-six patients recovered and 21 died. The average age and body mass index (BMI) of the deceased group were significantly higher than those of the recovered group (69.81±6.80 years vs 60.79±11.28 years, P<0.001 and 24.95±3.14 kg/m² vs 23.09±2.97 kg/m², P=0.014, respectively). The combination of antiviral drugs and supportive therapy appears to be associated with the lowest mortality (P<0.05). Multivariate Cox regression analysis revealed that age, BMI, H-CRP, shock, and acute respiratory distress syndrome (ARDS) were independent risk factors for patients with COVID-19 (P<0.05). CONCLUSIONS Elderly patients and those with a high BMI, as well as patients who experience shock and ARDS, may have a higher risk of death from COVID-19. The combination of antiviral drugs and supportive therapy appears to be associated with lower mortality, although further research is needed.

First-Line Vasopressor and Mortality Rates in ED Patients with Acute Drug Overdose.

INTRODUCTION: While emergency department (ED) visits for acute drug overdose are at an all-time high, the importance of vasopressors to treat circulatory shock in this patient population remains unclear. This study investigated the association between first-line vasopressor and mortality, for both push-dose and infusion, in this patient population. METHODS: From a prospective cohort of consecutive ED patients with drug overdose at two urban teaching centers over 5 years, we performed a secondary data analysis of patients with circulatory shock, defined as hypotension requiring either vasopressors, high-dose insulin euglycemia therapy, or both. The first-line vasopressor (push-dose and infusion) was analyzed for associations with the primary outcome (in-hospital mortality) and secondary outcomes (24-hour mortality, ICU LOS). Subgroup analysis of beta-/calcium-channel blocker overdose was performed to evaluate impact of antidotal therapies. Data analysis included multivariable regression. RESULTS: Fifty-five patients with circulatory shock were analyzed, in whom there was 20% 24-hour mortality, 42% in-hospital mortality, 730-minute mean vasopressor duration, and 53.4-hour median ICU LOS. On multivariable analysis, there was significantly decreased adjusted odds of in-hospital mortality with first-line push-dose phenylephrine (aOR 0.06, CI 0.01-0.55), and significantly increased adjusted odds of in-hospital mortality with first-line push-dose epinephrine (aOR 60.8, CI 6.1-608). Of the first-line infusions, norepinephrine had the lowest odds of in-hospital mortality (aOR 0.80, CI 0.2-3.1). CONCLUSIONS: In ED patients with undifferentiated drug overdose and circulatory shock, the first-line vasopressor is associated with in-hospital mortality. First-line push-dose phenylephrine was associated with the lowest odds of in-hospital mortality. Future randomized studies are warranted for validation.

Effect of shenfu injection on microcirculation in shock patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Shock is a major public health problem worldwide. At present, the morbidity and mortality of shock patients are relatively high. Vasomotor dysfunction is 1 of the key pathological aspects of shock. Shenfu injection has been widely used for the treatment of shock in China. Pharmacological studies have suggested that Shenfu injection can reduce peripheral circulation resistance and improve microcirculation. The purpose of this study is to evaluate the effect and safety of Shenfu injection on the microcirculation of patients with shock. METHODS: This review summarizes and meta-analyzes randomized controlled trials of Shenfu injection for the treatment of shock.Searched the following electronic databases: PubMed, Cochrane Library, Embase, CNKI, VIP and Wanfang Data. The Cochrane risk assessment tool was used to evaluate the methodological quality of randomized controlled trials. All tests are analyzed according to the standards of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software and Grading of Recommendations Assessment, Development, and Evaluation pro GDT web solution are used for data synthesis and analysis. RESULTS: This review focuses on the effects of Shenfu injection on the microcirculation of shock patients (blood lactic acid level, arteriovenous oxygen saturation, arteriovenous carbon dioxide partial pressure difference, sublingual microcirculation), 28-day mortality, 28-day ICU hospitalization and adverse reaction rate. CONCLUSION: This review provides a clear basis for evaluating the impact of Shenfu injection on the microcirculation of shock patients, as well as the effectiveness and safety of the treatment.

Subacute uterine inversion following an induced abortion in a teenage girl: a case report.

BACKGROUND: Subacute uterine inversion is a very rare complication of mid-trimester termination of pregnancy that should be considered in a situation where unsafe abortion occurs. CASE PRESENTATION: We present a case of subacute uterine inversion complicated by hypovolemic shock following an unsafe abortion in a 17-year-old nulliparous unmarried girl. She presented with a history of collapse, mass protruding per vagina that followed Valsalva, and persistent lower abdominal pain but not vaginal bleeding. This followed her second attempt to secretly induce an abortion at 18 weeks amenorrhea. On examination, she was agitated, severely pale, cold on palpation, with an axillary temperature of 35.8 °C, a tachycardia of 143 beats per minute and unrecordable low blood pressure. The abdomen was soft and non-tender with no palpable masses; the uterine fundus was absent at its expected periumbilical position and cupping was felt instead. A fleshy mass with gangrenous patches protruding in the introitus was palpated with no cervical lip felt around it. We made a clinical diagnosis of subacute uterine inversion complicated with hypovolemic shock and initiated urgent resuscitation with crystalloid and blood transfusion. Non-operative reversal of the inversion failed. Surgery was done to correct the inversion followed by total abdominal hysterectomy due to uterine gangrene. CONCLUSION: Our case highlights an unusual presentation of subacute uterine inversion following unsafe abortion. This case was managed successfully but resulted in significant and permanent morbidity.

Vitamin B6 prevents excessive inflammation by reducing accumulation of sphingosine-1-phosphate in a sphingosine-1-phosphate lyase-dependent manner.

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.

Medication as a risk factor for hospitalization due to heart failure and shock: a series of case-crossover studies in Swiss claims data.

PURPOSE: Heart failure is among the leading causes for hospitalization in Europe. In this study, we evaluate potential precipitating factors for hospitalization for heart failure and shock. METHODS: Using Swiss claims data (2014-2015), we evaluated the association between hospitalization for heart failure and shock, and prescription of oral potassium supplements, non-steroidal anti-inflammatory drugs (NSAIDs), and amoxicillin/clavulanic acid. We conducted case-crossover analyses, where exposure was compared for the hazard period and the primary control period (e.g., 1-30 days before hospitalization vs. 31-60 days, respectively). Conditional logistic regression was applied and subsequently adjusted for addressing potential confounding by disease progression. Sensitivity analyses were conducted and stratification for co-medication was performed. RESULTS: We identified 2185 patients hospitalized with heart failure or shock. Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid was significantly associated with an increased risk for hospitalization for heart failure and shock with crude odds ratios (OR) of 2.04 for potassium (95% CI 1.24-3.36, p = 0.005, 30 days), OR 1.8 for NSAIDs (95% CI 1.39-2.33, p < 0.0001, 30 days), and OR 3.25 for amoxicillin/clavulanic acid (95% CI 2.06-5.14, p < 0.0001, 15 days), respectively. Adjustment attenuated odds ratios, while the significant positive association remained (potassium OR 1.70 (95% CI 1.01-2.86, p = 0.046), NSAIDs OR 1.50 (95% CI 1.14-1.97, p = 0.003), and amoxicillin/clavulanic acid OR 2.26 (95% CI 1.41-3.62, p = 0.001). CONCLUSION: Prescription of potassium supplements, NSAIDs, and amoxicillin/clavulanic acid is associated with increased risk for hospitalization. Underlying conditions such as pain, electrolyte imbalances, and infections are likely contributing risk factors. Physicians may use this knowledge to better identify patients at risk and adapt patient management.

Safety, Pharmacodynamics, and Efficacy of High- Versus Low-Dose Ascorbic Acid in Severely Burned Adults.

In sepsis and burns, ascorbic acid (AA) is hypothesized advantageous during volume resuscitation. There is uncertainty regarding its safety and dosing. This study evaluated high dose AA (HDAA: 66 mg/kg/h for 24 hours) versus low dose AA (LDAA: 3.5 g/days) administration during the first 24 hours in severely burned adults. We conducted a retrospective study comparing fluid administration before and after switching from low dose to HDAA in severely burned adults. A total of 38 adults with burns >20% TBSA, who received either HDAA or LDAA were included in this retrospective study. AA serum concentrations were quantified at 0, 24, and 72 hours postburn. HDAA impact on hemodynamics, acid-base homeostasis, acute kidney injury, vasopressor use, resuscitation fluid requirement, urinary output, and the incidence of adverse effects was evaluated; secondary clinical outcomes were analyzed. AA plasma levels were 10-fold elevated in the LDAA and 150-fold elevated in the HDAA group at 24 hours and decreased in both groups afterwards. HDAA was not associated with a significantly increased risk of any complications. A significant reduction in colloid fluid requirements was noted (LDAA: 947 ± 1722 ml/24 hours vs HDAA: 278 ± 667 ml/24 hours, P = 0.029). Other hemodynamic and resuscitation measures, as well as secondary clinical outcomes were comparable between groups. HDAA was associated with higher AA levels and lower volumes of colloids in adults with severe burns. The rate of adverse events was not significantly higher in patients treated with HDAA. Future studies should consider prolonged administration of AA.

Myocardial edema in paroxysmal permeability disorders: The paradigm of Clarkson's disease.

PURPOSE: Paroxysmal Permeability Disorders (PPDs) comprise a variety of diseases characterized by recurrent and transitory increase of endothelial permeability. Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a rare PPD that leads to an abrupt massive shift of fluids and proteins from the intravascular to the interstitial compartment. In some cases, tissue edema may involve the myocardium, but its role in the development of shock has not been elucidated so far. MATERIALS AND METHODS: Assessment of cardiac involvement during ten life-threatening ISCLS episodes admitted to ICU. RESULTS: Transthoracic echocardiographic examination was performed in eight episodes, whereas a poor acoustic window prevented cardiac ultrasound assessment in two episodes. Myocardial edema was detected by echocardiography in eight episodes and marked pericardial effusion in one-episode. Cardiac magnetic resonance showed diffuse myocardial edema in another episode. In one case, myocardial edema caused fulminant left ventricular dysfunction, which required extracorporeal life support. The mean septum thickness was higher during the shock phase compared to the recovery phase [15.5 mm (13.1-21 mm) vs. 9.9 mm (9-11.3 mm), p = .0003]. Myocardial edema resolved within 72 h. CONCLUSIONS: During early phases of ISCLS, myocardial edema commonly occurs and can induce transient myocardial dysfunction, potentially contributing to the pathogenesis of shock.

Derangement of PaCO2 requires physician attention in acute carbon monoxide poisoning.

The objective was to describe the prevalence of derangement of the partial pressure of arterial carbon dioxide (PaCO2) and to determine the association between PaCO2 and adverse cardiovascular events (ACVEs) in carbon monoxide (CO)-poisoned patients. Additionally, we evaluated whether the derangement of PaCO2 was simply secondary to metabolic changes. This retrospective study included 194 self-breathing patients after CO poisoning with an indication for hyperbaric oxygen therapy and available arterial blood gas analysis at presentation and 6 h later. The incidence rate of hypocapnia at presentation after acute CO poisoning was 67.5%, and the mean PaCO2 during the first 6 h was 33 (31-36.7) mmHg. The most common acid-base imbalance in 131 patients with hypocapnia was primary respiratory alkalosis. The incidence rate of ACVEs during hospitalization was 50.5%. A significant linear trend in the incidence of ACVEs was observed across the total range of PaCO2 variables. In multivariate regression analysis, mean PaCO2 was independently associated with ACVEs (odds ratio 0.051; 95% confidence interval 0.004-0.632). PaCO2 derangements were common after acute CO poisoning and were not explainable as a mere secondary response to metabolic changes. The mean PaCO2 during the first 6 h was associated with ACVEs. Given the high incidence of ACVEs and PaCO2 derangement and the observed association between the mean PaCO2 and ACVEs, this study suggests that (1) PaCO2 should be monitored in the acute stage to predict and/or prevent ACVEs and (2) further investigation is needed to validate this result and explore the early manipulation of PaCO2 as a treatment strategy.

Cardiac Collapse Secondary to Phenytoin Toxicity in a Neonate Treated with Extracorporeal Membrane Oxygenation Support (ECMO).

INTRODUCTION: Although medication toxicity is uncommon in neonates, there are several medications used in this population that pose a risk. Phenytoin has an increased risk of toxicity given its narrow therapeutic window and variations in drug elimination. CASE REPORT: We describe the case of a 3-day-old male infant who developed cardiovascular collapse secondary to severe phenytoin toxicity (max phenytoin level 86 µg/mL) and was placed on extracorporeal membrane oxygenation support (ECMO). Several ancillary treatments were utilized in an attempt to decrease serum phenytoin concentrations and limit toxicity including albumin boluses, phenobarbital administration, intravenous lipid infusion, and folic acid supplementation. DISCUSSION: Although uncommon, drug toxicity should be considered in patients with acute changes who are exposed to medications with potential toxicity. With elevated levels of phenytoin, the half-life can be prolonged resulting in longer exposure to elevated levels of the drug as seen in our patient. This case report highlights the importance of ECMO utilization for cardiac support in neonates with medication toxicity and other potential ancillary treatments to decrease serum phenytoin concentrations.

Differences in effect of early enteral nutrition on mortality among ventilated adults with shock requiring low-, medium-, and high-dose noradrenaline: A propensity-matched analysis.

BACKGROUND & AIMS: Despite extensive research on early enteral nutrition (EEN), it remains unclear whether EEN is effective for patients with shock requiring vasopressors. This study aimed to compare outcomes between EEN and late enteral nutrition (LEN) in ventilated patients with shock requiring low-, medium-, or high-dose noradrenaline. METHODS: Using a national inpatient database in Japan, we identified ventilated patients admitted to intensive care units who had shock requiring catecholamines (noradrenaline or dobutamine) from July 2010 to March 2016. We defined patients who started enteral nutrition within 2 days after starting mechanical ventilation as EEN group and the others as LEN group. Propensity score matching was performed between patients undergoing EEN and LEN in each of the low- (<0.1 µg/kg/min), medium- (0.1-0.3 µg/kg/min), and high-dose (≥0.3 µg/kg/min) noradrenaline groups. RESULTS: We identified 52,563 eligible patients during the 69-month study period, including 38,488, 11,042, and 3033 patients in the low-, medium-, and high-dose noradrenaline groups, respectively. One-to-two propensity score matching created 5,969, 2,162, and 477 one-to-two matched pairs in the low-, medium-, and high-dose noradrenaline groups, respectively. The 28-day mortality rate was significantly lower in the EEN than LEN group in the low-dose noradrenaline group (risk difference, -2.9%; 95% confidence interval [CI], -4.5% to -1.3%) and in the medium-dose noradrenaline group (risk difference, -6.8%; 95% CI, -9.6% to -4.0%). In the high-dose noradrenaline group, 28-day mortality did not differ significantly between the EEN and LEN groups (absolute risk difference, -1.4%; 95% CI, -7.4%-4.7%). CONCLUSIONS: Although the size of the subgroup requiring high-dose noradrenaline may have been too small to demonstrate a significant difference, the results suggest that EEN was associated with a reduction in mortality in ventilated adults treated with low- or medium-dose noradrenaline but not in those requiring high-dose noradrenaline.