Received Fluid Resuscitation Research Articles

7506 Rare Case of Hyperparathyroidism in Third Trimester Pregnancy Requiring Urgent Parathyroidectomy

Abstract Disclosure: A. Rothstein Costris: None. E. Davydov: None. S. Levy: None. Introduction: Primary hyperparathyroidism (PHPT) during pregnancy has risks to both the mother and her fetus. Complications include maternal pre-eclampsia, miscarriage, hyperemesis gravidarum, nephrolithiasis and pancreatitis. Fetal complications encompass hypocalcemia, tetany, intrauterine growth retardation and fetal demise. Though medical treatment is available, parathyroidectomy is the only definitive treatment. Traditionally, surgery is done in the second trimester of pregnancy. We report a case of a third trimester parathyroidectomy in a 29 yo female with PHPT. Case representation: A 29-year-old G1P0 woman at 28 weeks gestation presented with persistent nausea and vomiting, constipation, joint pain, and increased forgetfulness. She has moved to USA from Saudi Arabia and had not received prenatal care in the USA. She was found to have a PTH of 224 (15-65 pg/mL), Calcium of 13.5 (8.2-10.2 mg/dL), Ionized Calcium of 1.63 (1.00-1.35 mmol/L), and a corrected Calcium of 14.2 (8.7-10.1 mg/dL). Electrolyte abnormalities were also noticed, with a Potassium of 2.8 (3.5-5 mmol/L), Phosphorus of 1.7 (2.5-4.5 mg/dL) and Magnesium of 1.2 (1.8-2.3 mg/dL). Vit. D levels were found to be extremely low <7 (20-40 ng/mL). Due to severe dehydration, persistent nausea, vomiting, and hypercalcemia, the patient received fluid resuscitation and Vit. D supplementation. A neck CT scan identified an 11 x 6 x 14 mm arterially hyperenhancing soft tissue structure at T1-T2, suggesting a probable parathyroid adenoma in the right paratracheal region. Management options included surgery or conservative therapy with fluids and Cinacalcet. A joint decision was made between Maternal Fetal Medicine, ENT and Endocrinology to proceed with parathyroidectomy. Surgical excision revealed an enlarged, hypercellular right inferior parathyroid gland (0.51g). Postoperative laboratory studies at 2 weeks showed normal PTH, Ca, Ionized Ca. Conclusion: It is preferable to conduct surgery for PHPT during the second trimester of pregnancy. However, when PHPT leads to severe symptoms, surgery might be considered in the third trimester. The severity of our patient’s symptoms led to inability to tolerate oral intake, deeming surgery necessary. The multidisciplinary team agreed that surgery in the third trimester would be the best course of treatment as it will result in normocalcemia immediately. Second trimester parathyroidectomy is viewed as safer due to the completion of organogenesis and lower teratogenicity risks. Performance of surgery during the third trimester may lead to an increase in the risk of premature birth. However, untreated hypercalcemia may increase fetal loss and thus third trimester parathyroidectomy can be considered as a treatment option for PHPT in pregnancy. It is also imperative to discuss all options with the patient. In our case, the patient had opted for surgery which was successful. Presentation: 6/3/2024

Peripartum Torpor: A Chilling Case Report and Review of the Literature

Purpose: To report a rare case of peripartum maternal hypothermia and bradycardia. Methods: Case report. Results: Torpor is a transient state of hibernation with hypothermia and bradycardia. Hypothermia is defined as an abnormally low core body temperature less than 36°C.1 Sinus bradycardia is defined as less than 60 beats/min. While occasionally hypothermia or bradycardia is seen in obstetric patients undergoing vaginal delivery, when combined together, it can be a rare, life-threatening state that requires prompt intervention to prevent adverse maternal and fetal outcomes. A 23 year-old G2P0102 at 33+3 weeks of gestation was admitted to the high risk obstetric service for preterm labor complicated by fetal growth restriction. She had a history of preeclampsia in a previous pregnancy, but otherwise denied any chronic medical problems. Upon arrival, her vital signs showed a temperature of 37°C, a pulse of 53 bpm, and blood pressure of 126/62 mmHg. Her white blood cell count was 12.4 x 109/L and hemoglobin was 11.3 g/dL. She received betamethasone for fetal lung maturity and penicillin for Group B streptococcus prophylaxis. As her cervix continued to dilate, she received an epidural for pain management. Once she was in active labor, she became bradycardic with a pulse in the 30s-40s bpm, as confirmed by EKG. She was completely asymptomatic at this time, and fetal heart tones were reassuring with a baseline between 110’s-130’s bpm. She delivered vaginally with 150 mL of estimated blood loss, and her bradycardia continued postpartum even after the epidural was discontinued. When she complained of feeling cold, multiple attempts with different oral and axillary thermometers could not obtain a reading. She was warmed with forced-air warming blankets, warmed blankets, and hot packs in her groin and axilla. During this time, discussion with the NICU staff revealed that her baby was also hypothermic at 33.3°C and hypoglycemic at 28 mg/dL at birth. Other than feeling cold, the patient continued to be asymptomatic despite hypotension and bradycardia. She appeared somnolent but was responsive to questions. Her uterus was firm with minimal vaginal bleeding and no purulent or foul-smelling vaginal discharge. Repeat laboratory testing revealed a white blood count of 19 x 109/L and lactate was 3.3 mmol/L. Her comprehensive metabolic panel was unremarkable. A chest x-ray was clear. A C-reactive protein was < 0.3 mg/dL and sedimentation rate was 14 mm/h. A rectal continuous thermometer was placed, which eventually recorded a temperature at 33.3°C and upon recheck was 31.7°C. A multidisciplinary team, including Anesthesia, Internal Medicine, and Neurology, evaluated the patient due to concern for a central nervous system insult. She received fluid resuscitation and broad-spectrum antibiotics for sepsis protocol. Due to the concern for potential septic shock, the decision was made to transport her to the Medical ICU for further management. As she was leaving Labor & Delivery, her temperature had increased to 36.9°C and her pulse to 61. Thyroid studies the next day revealed a normal Free T4 of 1.00 ng/dL and a high thyroid stimulating hormone level of 9.55 uIU/mL. However, despite an extensive workup, no clear etiology of her hypothermia and bradycardia was identified. Intervention with fluids and application of forced-air warming system resolved the hypothermia in less than 6 hours without relapse. Antibiotics were discontinued after one day due to low suspicion for systemic infection. She remained vitally stable and was discharged on postpartum day 2 without further complications. Conclusions: Maternal hypothermia is relatively common during cesarean delivery; however, very few cases report maternal hypothermia during vaginal delivery. An English language literature search for maternal hypothermia during vaginal delivery yielded less than 10 case reports – few of which identified a cause of the hypothermia – and none of which reported simultaneous maternal bradycardia. While our case is a very rare presentation and the etiology is still unknown, it highlights the importance of prompt recognition of vital sign derangements in peripartum patients as well as multidisciplinary attention.

How a positive fluid balance develops in acute kidney injury: A binational, observational study

PurposeA positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients. MethodsMultinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy. ResultsAKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9–89.2), nutritional intake (median:18.2 mL/h; IQR 0.0–45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0–96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05–1.19;p-value <0.001). ConclusionAmong ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB. Key pointsQuestionHow does a positive fluid balance develop in critically ill patients with acute kidney injury?FindingsCumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy.MeaningCurrent management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use.

1039 Preventing Avoidable Harm with Safe IV Fluid Therapy – a Closed Loop Audit

Abstract Aim The National Institute for Health and Care Excellence (NICE) states that one in five people on intravenous (IV) fluids suffer from complications or morbidity due to their inappropriate administration. We aimed to compare our Trust’s current IV fluid prescription practices to standards set out in the NICE CG174 guidelines. Method We retrospectively reviewed 50 case notes for patients admitted to the Acute Medical Unit. We evaluated if hydration status was assessed comprehensively, and if resuscitation and maintenance fluids were prescribed appropriately, according to the NICE CG174 guidelines. The findings were presented at a local meeting and interventions were implemented by putting up posters and conducting regular teaching sessions on safe IV fluid prescription. To close the audit loop, data from a further 50 patients was collected post-intervention. Results The first audit cycle showed poor overall compliance with the guidelines; however a significant improvement was noted post-intervention. Pre-intervention, only 10% of patients had regular hydration assessments, 32% of patients received fluid resuscitation appropriately, and while 52% of our sample received maintenance fluid when indicated, 0% received the correct composition. Post-intervention, these figures rose to 28%, 66%, 84% and 15% respectively. Conclusions Inappropriate fluid administration is a risk to patient safety. This audit highlighted several areas for improvement regarding IV fluid prescription, and although a significant change was noted, further work is needed to increase compliance. We hope to incorporate the topic of IV fluids into the hospital’s regular teaching programmes to sustainably improve IV fluid prescription practices across the Trust.

Relationship between the rate of fluid resuscitation and acute kidney injury: A retrospective cohort study.

Septic shock is the leading cause of acute kidney injury (AKI) in critically ill patients. The foundation of early septic shock management includes early fluid resuscitation, but the association between fluid resuscitation rates and kidney outcomes remains unclear. This investigation examines the association between fluid resuscitation rate and AKI recovery. In the medical intensive care unit of Mayo Clinic Rochester, adult patients with AKI and septic shock were retrospectively studied from January 1, 2006 to May 31, 2018. The surviving sepsis campaign recommends an initial fluid bolus of 30 ml/kg for sepsis resuscitation. The cohort of patients was divided into three groups based on the average fluid resuscitation time (<1 h, 1.1-3 h, >3 h) and the corresponding fluid rate ≥0.5, 0.17-0.49, and <0.17 ml/kg/min, respectively. The primary outcome was the recovery of AKI on day 7. To account for potential confounders, multivariable regression analyses were conducted. After meeting the eligibility, 597 patients were included in the analysis. The AKI recovery was considerably different among the groups (P = 0.006). Patients in group 1 who received fluid resuscitation faster had a higher rate of AKI recovery (53%) compared to group 2 and group 3 (50% and 37.8%). In septic shock patients with AKI, a higher fluid resuscitation rate of 30 ml/kg IV fluids within the 1st-h sepsis diagnosis (i.e., >0.50 ml/kg/min) lead to higher AKI recovery compared with slower infusion rates.

Epidemiology and clinical characteristics of pediatric sepsis in PICUs of China: A national cross-sectional study.

Epidemiology and clinical characteristics of pediatric sepsis in PICUs of China: A national cross-sectional study.

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. A single-center prospective cohort study from January to December 2021. Twelve medical-surgical PICU beds at a university hospital. Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. None. We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

Adding heart rate n-variability (HRnV) to clinical assessment potentially improves prediction of serious bacterial infections in young febrile infants at the emergency department: a prospective observational study.

We aim to investigate the utility of heart rate variability (HRV) and heart rate n-variability (HRnV) in addition to vital signs and blood biomarkers, among febrile young infants at risk of serious bacterial infections (SBIs). We performed a prospective observational study between December 2017 and November 2021 in a tertiary paediatric emergency department (ED). We included febrile infants <90 days old with a temperature ≥38 ℃. We obtained HRV and HRnV parameters via a single lead electrocardiogram. HRV measures beat-to-beat (R-R) oscillation and reflects autonomic nervous system (ANS) regulation. HRnV includes overlapping and non-overlapping R-R intervals and provides additional physiological information. We defined SBIs as meningitis, bacteraemia and urinary tract infections (UTIs). We performed area under curve (AUC) analysis to assess predictive performance. We recruited 330 and analysed 312 infants. The median age was 35.5 days (interquartile range 13.0-61.0); 74/312 infants (23.7%) had SBIs with the most common being UTIs (66/72, 91.7%); 2 infants had co-infections. No patients died and 32/312 (10.3%) received fluid resuscitation. Adding HRV and HRnV to demographics and vital signs at ED triage successively improved the AUC from 0.765 [95% confidence interval (CI): 0.705-0.825] to 0.776 (95% CI: 0.718-0.835) and 0.807 (95% CI: 0.752-0.861) respectively. The final model including demographics, vital signs, HRV, HRnV and blood biomarkers had an AUC of 0.874 (95% CI: 0.828-0.921). Addition of HRV and HRnV to current assessment tools improved the prediction of SBIs among febrile infants at ED triage. We intend to validate our findings and translate them into tools for clinical care in the ED.

Longitudinal profile of routine biomarkers for mortality prediction using unsupervised clustering algorithm in severely burned patients: a retrospective cohort study with prospectively collected data.

Burn injury has high clinical heterogeneity and worse prognosis in severely burned patients. Clustering algorithms using unsupervised methods to identify groups with similar trajectories in heterogeneous disease patients can provide insight into mechanisms of disease pathogenesis. This study analyzed routinely collected biomarkers to evaluate mortality prediction, find clinical meanings for these or their subtypes, and evaluate patterns. This retrospective cohort study included patients aged >18 years, between July 2012 and June 2021. All eligible patients received fluid resuscitation and survived for at least 7 days. Characteristics of clinical interest to the physician at 4 clinically important time points were evaluated. Eligible patients were divided into 4 subgroups according to these time points: from 1st week to 4th week. Total of 1,249 patients admitted within 2 days after burns and receiving fluid resuscitation were included. Mean Harrell's C-index of pH was the highest (0.816), followed by platelets (0.807), creatinine (0.796), red cell distribution width (RDW, 0.778), and lactate (0.759). Longitudinal profiles among biomarkers were different. The main predictors were pH, platelets, creatinine, RDW, and lactate. Creatinine and RDW showed consistent patterns. The other markers varied according to patient condition. Thus, these markers could provide clues into underlying mechanisms and predict mortality.

Calcium-alkali syndrome as a rare cause of severe hypercalcemia requiring dialysis in early twin gestation.

Hypercalcemia is rare in women of child-bearing age, and most cases are due to primary hyperparathyroidism. A 28-year-old woman, 14 weeks pregnant with dichorionic diamniotic twins, presented to hospital with vomiting, muscle cramps, and weakness. She had been taking calcium carbonate for gastric reflux and nausea from 5 weeks of gestation. Investigations revealed severe hypercalcemia, metabolic alkalosis, and renal injury. She was transferred to intensive care, receiving fluid resuscitation and subcutaneous calcitonin followed by dialysis. Investigations revealed suppressed PTH and PTH-related peptide, negative malignancy screening and low vitamin D level. Calcium and renal function quickly normalized and with cessation of calcium carbonate remained normal throughout the rest of pregnancy. Reports of calcium-alkali syndrome causing severe hypercalcemia are scarce, with most cases occurring later in gestation. This case represents a dramatic presentation requiring renal replacement therapy early in twin gestation.

478: REFRACTORY TOXIC SHOCK SYNDROME: IV IMMUNOGLOBULIN TO THE RESCUE!

Introduction: Streptococcal toxic shock syndrome (TSS) is one of the most severe manifestations of Group A Streptococcus (GAS). Despite adequate treatment, morbidity and mortality still remains high. We present a case of necrotizing fasciitis complicated by streptococcal TSS that was refractory to standard treatment and was ultimately treated successfully with intravenous immunoglobulin (IVIG). Description: A 63-year-old female with history of hypertension, morbid obesity and asthma presented to ED with a 1-week history of fever, malaise, and left thigh pain (no history of leg injury). Upon evaluation, patient’s left leg was noted to have multiple scabs and warmth in the left inguinal area. MRI of the left femur showed severe superficial and deep edema with cellulitis, concerning for necrotizing fasciitis. Labs were remarkable for leukocytosis 16.6 k/uL, creatinine 2.28 mg/dL and lactate 6 mmol/L. She received fluid resuscitation and was initiated on empiric antibiotic therapy with clindamycin, piperacillin-tazobactam and vancomycin. She had a rapid hemodynamic deterioration and required intubation and multiple vasopressors. She was taken to OR for emergent debridement and was admitted to the ICU postoperatively. Wound cultures were found positive for GAS and the diagnosis of STSS was made. Despite multiple wound debridement and amikacin therapy, patient failed to improve clinically. The decision was made to administer intravenous immunoglobulin as a rescue therapy. She was premedicated with diphenhydramine, hydrocortisone, and acetaminophen. She received IVIG at 1 g/kg/day for 1 day followed by 0.5 g/kg for another 2 days. The patient showed significant improvement post IVIG therapy and was subsequently transferred to the regular nursing floor after a few days. Discussion: Necrotizing fasciitis from GAS with streptococcal TSS has a very high mortality rate. Treatment includes aggressive wound debridement with gram positive and negative antibiotic coverage. Clindamycin is also used to inhibit toxin production. IVIG can be effective in treating TSS refractory to conventional treatment by neutralizing superantigens. The efficacy of IVIG in treating TSS has been variable across multiple studies, but our case highlights the efficacy of IVIG in toxic shock syndrome refractory to standard therapy.

LEGIONNAIRES DISEASE: A CASE WITH SEVERE NEUROLOGIC AND RENAL INVOLVEMENT

LEGIONNAIRES DISEASE: A CASE WITH SEVERE NEUROLOGIC AND RENAL INVOLVEMENT

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

Use of Albumin as a Resuscitative Fluid in the Intensive Care Unit.

Effect of milrinone versus placebo on hemodynamic in patients with septic shock: A randomize control trial

Background: Sepsis is one of the most serious healthcare problems worldwide, which is associated with high mortality and financial burdens. The common causes of death are refractory shock and multi-organ failure. Myocardial dysfunction, a relatively common complication of septic shock, causes a significantly decrease in stroke volume and cardiac output. This results in insufficient blood supply to the organs, creates multi-organ failure and finally, leading to death. The Surviving Sepsis Campaign Guidelines 2016 also recommended using dobutamine in septic shock patients who had been resuscitated until achieving normal blood pressure target of mean arterial pressure 65 mmHg or more, but still had evidence of inadequate tissue perfusion. Milrinone action via an alternative pathway from the sympathetic inotropic agents, makes the milrinone to be used as an option for improve cardiac function among sepsis patients. However, there are few studies of milrinone in patients with septic shock. Methods: We plan to conduct a double blind randomized controlled trial, enrolling patients at Siriraj hospital and Hat-Yai hospital. The adults with the diagnosis of septic shock according to definition of SEPSIS III will be screened. Patients who receive fluid resuscitation at least 30 mL/kg, mean arterial pressure (MAP) ≥ 65 mmHg, with a clinical sign of poor tissue perfusion, or evidence of impaired left ventricular systolic function (left ventricular ejection fraction (LVEF) &lt; 40%) will be enrolled. The patients were randomly assigned in a 1:1 ratio by their sequential number to receive either milrinone (intervention group) or placebo (control group). The physician performs an echocardiogram for assessing cardiac function, before the starting of the study drug and after the 6 and 24 hours. The monitoring of vital signs, urine output, and lactate at 6 and 24 hours after milrinone or placebo commencement is recorded. Conclusion: This study will evaluate the efficacy of milrinone in improving cardiac output among adult patients with septic shock who is resuscitated to achieve target blood pressure but still have signs of poor tissue perfusion.

Effects of fluids vs. vasopressors on spinal cord microperfusion in hemorrhagic shock induced ischemia/reperfusion

ObjectiveSpinal cord injury induced by ischemia/reperfusion is a devastating complication of aortic repair. Despite developments for prevention and treatment of spinal cord injury, incidence is still considerably high majorly impacting patient outcome. Microcirculation is paramount for tissue perfusion and oxygen supply and often dissociated from macrohemodynamic parameters used to guide resuscitation. Effects of fluids vs. vasopressors in the setting of hemodynamic resuscitation on spinal cord microperfusion are unknown. Aim of this study was to compare the effects of vasopressor and fluid resuscitation on spinal cord microperfusion in a translational acute pig model of hemorrhagic shock induced ischemia/reperfusion injury. MethodsWe designed this study as prospective randomized explorative large animal study. We induced hemorrhagic shock in 20 pigs as a model of global ischemia/reperfusion injury. We randomized animals to receive either fluid or vasopressor resuscitation. We measured spinal cord microperfusion using fluorescent microspheres as well as laser-Doppler probes. We monitored and analyzed macrohemodynamic parameters and cerebrospinal fluid pressure. ResultsSpinal cord microperfusion decreased following hemorrhagic shock induced ischemia/reperfusion injury. Both fluids and vasopressors sufficiently restored spinal cord microperfusion. There were no important changes between groups (percentage changes compared to baseline: fluids 14.0 (0.31–27.6) vs. vasopressors 24.3 (8.12–40.4), p = .340). However, cerebrospinal fluid pressure was higher in animals receiving fluid resuscitation (percentage changes compared to baseline: fluids 27.7 (12.6–42.8) vs. vasopressors −5.56 ((−19.8)–8.72), p = .003). Microcirculatory resuscitation was in line with improvements of macrohemodynamic parameters. ConclusionsBoth, fluids and vasopressors, equally restored spinal cord microperfusion in a porcine acute model of hemorrhagic shock induced ischemia/reperfusion injury. However, significant differences in cerebrospinal fluid pressure following resuscitation were present. Future studies should evaluate these effects in perfusion disruption induced ischemia/reperfusion conditions of microcirculatory deterioration.

A Novel Risk Prediction Model for Severe Acute Kidney Injury in Intensive Care Unit Patients Receiving Fluid Resuscitation.

BackgroundTo develop a risk prediction model for the occurrence of severe acute kidney injury (AKI) in intensive care unit (ICU) patients receiving fluid resuscitation.MethodsWe conducted a secondary analysis of the Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) trial, a blinded randomized controlled trial that enrolled ICU patients who received intravenous fluid resuscitation. The primary outcome was the first event in a composite outcome of doubling of serum creatinine and/or treatment with renal replacement treatment (RRT) within 28 days of randomization. The final model developed using multivariable logistic regression with backwards elimination was validated internally and then translated into a predictive equation.ResultsSix thousand seven hundred twenty-seven ICU participants were studied, among whom 745 developed the study outcome. The final model having six variables, including admission diagnosis of sepsis, illness severity score, mechanical ventilation, tachycardia, baseline estimated glomerular filtration rate and emergency admission. The model had good discrimination (c-statistic = 0.72, 95% confidence interval 0.697–0.736) and calibration (Hosmer-Lemeshow test, χ2 = 14.4, p = 0.07) for the composite outcome, with a c-statistic after internal bootstrapping validation of 0.72, which revealed a low degree of over-fitting. The positive predictive value and negative predictive value were 58.8 and 89.1%, respectively. The decision curve analysis indicates a net benefit in prediction of severe AKI using the model across a range of threshold probabilities between 5 and 35%.ConclusionsOur model, using readily available clinical variables to identify ICU patients at high risk of severe AKI achieved good predictive performance in a clinically relevant population.

Efficacy analysis of inferior vena cava variability combined with difference of central venous-to-arterial partial pressure of carbon dioxide on guiding fluid resuscitation in patients with septic shock

To investigate the effect of inferior vena cava variability (IVCV) combined with difference of central venous-to-arterial partial pressure of carbon dioxide (Pcv-aCO2) on guiding fluid resuscitation in septic shock. Patients with septic shock admitted to the department of critical care medicine of Jiangxi Provincial People's Hospital from January 1, 2018 to December 31, 2020 were enrolled, and they were divided into control group and observation group according to random number table method. Patients in both groups were given fluid resuscitation according to septic shock fluid resuscitation guidelines. The patients in the control group received fluid resuscitation strictly according to the early goal-directed therapy (EGDT) strategy. Resuscitation target: central venous pressure (CVP) 12-15 cmH2O (1 cmH2O≈0.098 kPa), mean arterial pressure (MAP) > 65 mmHg (1 mmHg≈0.133 kPa), mean urine volume (UO) > 0.5 mL×kg-1×h-1, central venous oxygen saturation (ScvO2) > 0.70. In the observation group, the endpoint of resuscitation was evaluated by IVCV dynamically monitored by bedside ultrasound and Pcv-aCO2. Resuscitation target: fixed filling of inferior vena cava with diameter > 2 cm, IVCV < 18%, and Pcv-aCO2 < 6 mmHg. The changes in recovery indexes before and 6 hours and 24 hours of resuscitation of the two groups were recorded, and the 6-hour efficiency of fluid resuscitation, 6-hour lactate clearance rate (LCR) and 6-hour and 24-hour total volume of resuscitation were also recorded; at the same time, the duration of mechanical ventilation, length of intensive care unit (ICU) stay, 28-day mortality and the incidence of acute renal failure and acute pulmonary edema between the two groups were compared. A total of 80 patients were enrolled in the analysis, with 40 in the control group and 40 in the observation group. The MAP, CVP and ScvO2 at 6 hours and 24 hours of resuscitation in the two groups were significantly higher than those before resuscitation, while Pcv-aCO2 and blood lactic acid (Lac) were significantly decreased, and UO was increased gradually with the extension of resuscitation time, indicating that both resuscitation endpoint evaluation schemes could alleviate the shock state of patients. Compared with before resuscitation, IVCV at 6 hours and 24 hours of resuscitation in the observation group were decreased significantly [(17.54±4.52)%, (18.32±3.64)% vs. (27.49±10.56)%, both P < 0.05]. Compared with the control group, MAP and ScvO2 at 6 hours of resuscitation in the observation group were significantly increased [MAP (mmHg): 69.09±4.64 vs. 66.37±4.32, ScvO2: 0.666±0.033 vs. 0.645±0.035, both P < 0.05], 24-hour MAP was increased significantly (mmHg: 75.16±3.28 vs. 70.12±2.18, P < 0.05), but CVP was relatively lowered (cmH2O: 9.25±1.49 vs. 10.25±1.05, P < 0.05), indicating that the fluid resuscitation efficiency was higher in the observation group. Compared with the control group, 6-hour LCR in the observation group was significantly increased [(55.64±6.23)% vs. (52.45±4.52)%, P < 0.05], 6-hour and 24-hour total volume of resuscitation was significantly decreased (mL: 2 860.73±658.32 vs. 3 568.54±856.43, 4 768.65±1 085.65 vs. 5 385.34±1 354.83, both P < 0.05), the duration of mechanical ventilation was significantly shortened (days: 6.78±3.45 vs. 8.45±2.85, P < 0.05), while the incidence of acute pulmonary edema was significantly decreased [2.5% (1/40) vs. 20.0% (8/40), P < 0.05]. There was no significant difference in the length of ICU stay, 28-day mortality or incidence of acute renal failure between the two groups. Dynamic monitoring of IVCV and Pcv-aCO2 can effectively guide the early fluid resuscitation of patients with septic shock, and compared with EGDT, it can significantly shorten the duration of mechanical ventilation, reduce the amount of fluid resuscitation, and reduce the incidence of acute pulmonary edema. Combined with its non-invasive characteristics, it has certain clinical advantages.

Stevens-Johnson syndrome linked to tramadol use and ultraviolet radiation

Abstract Rationale: Stevens-Johnson syndrome (SJS) is a cutaneous reaction characterized by necrosis and epidermal detachment, commonly triggered by medications. Tramadol rarely causes SJS, and ultraviolet radiation (UVR) has limited recognition as being linked to SJS presentations. Patient concerns: A previously healthy 18-year-old female presented to the emergency department with what she believed to be a severe sunburn. Five days prior, she was exposed to extensive sun exposure while swimming all day at a lake. The following day, she developed a rash on her shoulders, which became widespread, extending to the palms of her hands and soles of her feet, and eventually involved her oral and ocular mucosa. At the time of hospital admission, the rash had progressed to form vesicles/bullae with skin sloughing and a positive Nikolsky sign, bleeding ulcers throughout the oral mucosa, and bilateral conjunctival hyperemia with purulent discharge. Diagnosis: The patient reported no medication use apart from a single dose of tramadol 7 to 10 days prior to rash onset. Given the clinical presentation and histopathological findings that were consistent with SJS, a diagnosis of SJS was made. The nature of this patient's rash onset, character, and progression suggests that UVR precipitated the event in conjunction with tramadol as the causative agent. Interventions: The patient received fluid resuscitation and was transferred via air ambulance to a trauma and burn center to receive treatment. Outcomes: Complete resolution of the patient's cutaneous and oral mucosal lesions occurred 4 weeks after discharge; however, hypopigmentation was evident in areas where cutaneous re-epithelialization had occurred. The patient was advised to strictly avoid the use of tramadol and limit her exposure to UVR. Lesson: Physicians should be aware that tramadol may cause SJS and that UVR may precipitate SJS in patients taking tramadol. Rapid diagnosis of SJS and transfer to a trauma or burn center improves patient outcomes.

Early Treatment With a Single Dose of Mesenchymal Stem Cell Derived Extracellular Vesicles Modulates the Brain Transcriptome to Create Neuroprotective Changes in a Porcine Model of Traumatic Brain Injury and Hemorrhagic Shock.

Cell-based therapies using mesenchymal stem cell derived extracellular vesicles (EVs) improve neurologic outcomes in animal models of traumatic brain injury (TBI), stroke, and hemorrhage. Using a porcine 7-day survival model of TBI and hemorrhagic shock (HS), we previously demonstrated that EV-treatment was associated with reduced brain lesion size, neurologic severity score, and cerebral inflammation. However, the underlying cellular and genomic mechanisms remain poorly defined. We hypothesize that EV treatment modulates the brain transcriptome to enhance neuroprotection and neurorestoration following TBI + HS. Swine were subjected to severe TBI (8-mm cortical impact) and HS (40% blood volume). After 1 h of shock, animals were randomized (n = 4/group) to treatment with either lactated Ringer's (LR) or LR + EV. Both groups received fluid resuscitation after 2 h of shock, and autologous packed red blood cells 5 h later.After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data were imported into the iPathway pipeline for bioinformatics analyses. 5,273 genes were differentially expressed in the LR + EV group versus LR alone (total 9,588 measured genes). Genes with the greatest upregulation were involved in synaptic transmission and neuronal development and differentiation, while downregulated genes were involved in inflammation. GO-terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed downregulation of inflammation, and upregulation of neurogenesis, and neuron survival and differentiation. In a porcine model of TBI + HS, EV treatment was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV treatment.

Early Transfusion with Mesenchymal Stem Cell Derived Extracellular Vesicles: A New Transfusion Strategy for Life-Threatening Hemorrhage and Traumatic Brain Injury

Background: Life-threatening hemorrhage and traumatic brain injury (TBI) have a significantly increasing global burden and remain leading causes of preventable deaths. Effective interventions may protect the brain against ongoing damage and improve the long-term outcomes. A growing area of interest is transfusion of cell-based therapies, particularly with bone marrow-derived mesenchymal stem cells (MSC). Transfusion using MSC derived extracellular vesicles (EVs) have shown to improve neurologic outcomes in animal models of life-threatening hemorrhage, stroke, and TBI. However, the precise mechanisms remain poorly characterized. In the present study, we aimed to elucidate some of the key cerebral genes, pathways, and networks that were modulated after transfusion of EVs in a porcine model of hemorrhagic shock (HS) and TBI.Methods: Swine were subjected to HS (40% blood volume) and severe TBI (8-mm cortical impact). After 1 hour of shock, animals were randomized (n=4/group) to treatment with either lactated Ringer's (LR) or LR+EV. Both groups received fluid resuscitation after 2 hours of shock, and autologous packed red blood cells 5 hours later. After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data was imported into the iPathway pipeline for bioinformatics analyses.Results: 5,273 genes were differentially expressed in the LR+EV group vs. LR alone (total 9,588 measured genes, Figure 1). Table 1 lists the top 10 genes exhibiting the greatest up- and down-expression based on fold change. Genes with the greatest up-regulation were involved in synaptic transmission and neuronal development and differentiation, while down-regulated genes were involved in inflammation. Gene Ontology terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed down-regulation of inflammation (Figure 2), and up-regulation of neurogenesis, and neuron survival and differentiation.Conclusions: In a porcine model of HS+TBI, EV transfusion was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV transfusion. EV transfusion reduces the hyper-inflammatory response and may have great promise in improving outcomes in concurrent life-threatening hemorrhage and severe TBI. Further testing of this novel strategy and its implications in transfusion medicine are warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.