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.).

Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial.

BACKGROUND & AIMS: Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels. RESULTS: There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly. CONCLUSIONS: In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival. LAY SUMMARY: Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.

Managing Heavy Menstrual Bleeding in Women at Risk of Thrombosis.

Management of heavy menstrual bleeding (HMB) in a woman with a history of thrombosis, or who is otherwise at high risk of thrombosis, or who takes medications for anticoagulation can present a challenge to health care providers. The goal of treating HMB is to reduce menstrual blood loss. First-line therapy is typically hormonal, and hormonal therapy can be contraindicated in women with a history of thrombosis unless they are on anticoagulation. As 70% of women on anticoagulation experience HMB, successful management of HMB may involve a modification in the anticoagulation or antiplatelet regimen, hormonal therapy tailored to the patient's situation, and/or surgical therapy.

Avoiding hemodynamic collapse during high-risk percutaneous coronary intervention: Advanced hemodynamics of impella support.

The rate of performing primary percutaneous coronary intervention in patients with complex coronary artery disease is increasing. The use of percutaneous mechanical circulatory support devices provides critical periprocedural hemodynamic support. Mechanical support has increased the safety and efficacy of interventional procedures in this high-risk patient population. Predicting patient response to the selected intervention can be clinically challenging. Here we demonstrate a case where complete hemodynamic collapse during PCI was avoided by mechanical support provided by the Impella device. Further, we employ a comprehensive cardiovascular model to predict ventricular function and patient hemodynamics in response to the procedure. New computational tools may help interventionists visualize, understand, and predict the multifaceted hemodynamic aspects of these high risk procedures in individual patients. © 2016 Wiley Periodicals, Inc.

Craniosynostosis and Guanine Nucleotide-binding Protein Alpha Stimulating Mutation: Risk of Bleeding Diathesis and Circulatory Collapse in Patients Undergoing Cranial Vault Reconstruction.

Reconstruction of the craniosynostosis deformity is a relatively safe operation with low overall complication risks. Despite expected risk of significant blood loss, life-threatening bleeding is relatively rare, and there is a low incidence of reported deaths in the literature. Several modalities have been described for perioperative mitigation of blood loss and transfusion requirements. Due to the low overall risk of life-threatening bleeding and circulatory collapse, it is judicious that any potential causes of such unusual but potentially significant fatal bleeding complication be evaluated and reported to increase awareness for craniofacial surgeons treating these conditions. In this report and literature review, the authors present a highly unusual patient with significant bone bleeding and circulatory collapse in a metopic craniosynostosis patient with guanine nucleotide-binding protein alpha stimulating (GNAS) mutation; perform a literature review regarding bleeding diathesis in craniosynostosis patients with GNAS mutations; and suggest guidelines to potentially prevent mortality in such patients.

Mechanical circulatory support in the new era: an overview.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

Intralipid in acute caffeine intoxication: a case report.

Caffeine is arguably the most widely used stimulant drug in the world. Here we describe a suicide attempt involving caffeine overdose whereby the patient's severe intoxication was successfully treated with the prompt infusion of Intralipid. A 19-year-old man was found in an agitated state at home by the volunteer emergency team about 1 h after the intentional ingestion of 40 g of caffeine (tablets). His consciousness decreased rapidly, followed quickly by seizures, and electrocardiographic monitoring showed ventricular fibrillation. Advanced life support maneuvers were started immediately, with the patient defibrillated 10 times and administered 5 mg epinephrine in total and 300 + 150 mg of amiodarone (as well as lidocaine and magnesium sulfate). The cardiac rhythm eventually evolved to asystole, necessitating the intravenous injection of epinephrine to achieve the return of spontaneous circulation. However, critical hemodynamic instability persisted, with the patient's cardiac rhythm alternating between refractory irregular narrow complex tachycardia and wide complex tachycardia associated with hypotension. In an attempt to restore stability we administered three successive doses of Intralipid (120 + 250 + 100 mg), which successfully prevented a severe cardiovascular collapse due to a supra-lethal plasma caffeine level (>120 mg/L after lipid emulsion). The patient survived without any neurologic complications and was transferred to a psychiatric ward a few days later. The case emphasizes the efficacy of intravenous lipid emulsion in the resuscitation of patients from non-local anesthetic systemic toxicity. Intralipid appears to act initially as a vehicle that carries the stimulant drug away from heart and brain to less well-perfused organs (scavenging mechanism) and then, with a sufficient drop in the caffeine concentration, possibly as a tonic to the depressed heart.

Pretreatment with Evans blue, a stimulator of BK(Ca) channels, inhibits compound 48/80-induced shock, systemic inflammation, and mast cell degranulation in the rat.

The present study demonstrated that intravenous injection of a high dose of compound 48/80 to the rat induced 50% drop, within a few min, in the mean arterial pressure and pulse pressure as well as systemic inflammatory plasma leakage that might lead to circulatory and respiratory failure. We also investigated whether pretreatment with Evans blue, a stimulator of BK(Ca) channels, could exert inhibitory effect against compound C48/80-induced allergic circulatory shock and systemic inflammation. Different groups of Sprague-Dawley rats received an intravenous injection of a dose of Evans blue (0, 5, 10, or 50 mg/kg) just 20 s prior to injection of compound 48/80 (200 µg/kg, over 2 min). The present study found that pretreatment with Evans blue in a dose of 10 or 50 mg/kg exerted acute inhibitory effect on compound 48/80-induced sudden drop in mean arterial and pulse pressures. We also showed that pretreatment with Evans blue in a dose of 5, 10, or 50 mg/kg significantly inhibited compound 48/80-induced extensive plasma extravasation, mast cell degranulation, and edema formation in various organs including the airways, esophagus, and skin. Pretreatment with Evans blue 50 mg/kg 1 h earlier exhibited longer-term inhibitory effect on compound 48/80-induced arterial hypotension and systemic inflammation. We concluded that Evans blue pretreatment prevented rats from compound 48/80-triggered allergic shock and systemic inflammation, possibly mainly through inhibition of mast cell degranulation. Evans blue might be potentially useful in elucidating the mechanism and acting as a therapeutic agent of allergic shock and systemic inflammation.

Attenuation of intestinal ischemic injury and shock by physostigmine.

BACKGROUND: Recently, protection in shock (hemorrhagic or septic) by physostigmine has been demonstrated. Here, we studied the protective effect of intravenous infusion of physostigmine in a rat model of severe intestinal ischemia-reperfusion (I/R) injury and shock. MATERIALS AND METHODS: Mesenteric I/R was induced in male Wistar rats by occlusion of the superior mesenteric artery (90 min) and subsequent reperfusion (120 min). Physostigmine (30 or 70 µg/kg) was administered as bolus injection before induction of I/R. One additional group received, subsequent to the bolus of 30-µg/kg physostigmine, a continuous infusion of 60-µg/kg physostigmine till the end of the experiment. RESULTS: Physostigmine at a dose of 70 µg/kg administered before I/R significantly decreased the macroscopically and microscopically visible intestinal damage. In addition to and presumably as a result of this local protective effect, physostigmine prevented shock induced by reperfusion of the ischemically injured intestine. Lower doses (30 µg/kg) or continuous application of physostigmine were less advantageous. CONCLUSIONS: Physostigmine is clearly protective in intestinal I/R injury and shock. However, for this purpose, physostigmine has to be applied at a dose (70 µg/kg), that is, approximately double the amount of the presently used clinical dose.

Outcomes of Percutaneous Coronary Intervention Performed With or Without Preprocedural Dual Antiplatelet Therapy.

BACKGROUND: Preprocedural dual antiplatelet therapy (DAPT) in percutaneous coronary interventions (PCI) has been shown to improve outcomes; however, the efficacy of the procedure and its complications in Japanese patients remain largely unexplored, so we examined the risks and benefits of DAPT before PCI and its association with in-hospital outcomes. METHODS AND RESULTS: We analyzed data from patients who had undergone PCI at 12 centers within the metropolitan Tokyo area between September 2008 and September 2013.Our study group comprised 6,528 patients, of whom 2,079 (31.8%) were not administered preprocedural DAPT. Non-use of preprocedural DAPT was associated with death, postprocedural shock, or heart failure (odds ratio [OR]: 1.47, 95% confidence interval [CI]: 1.10-1.96, P=0.009), and postprocedural myocardial infarction (OR: 1.41, 95% CI: 1.18-1.69, P<0.001) after adjusting propensity scores for known predictors of in-hospital complications. Non-use of DAPT was not associated with procedure-related bleeding complications (OR: 0.98, 95% CI: 0.71-1.59, P=0.764). CONCLUSIONS: Approximately one-third of the patients who underwent PCI did not receive preprocedural DAPT despite guideline recommendations. Our results indicate that patients undergoing PCI with DAPT have a lower risk of postprocedural cardiac events without any increased bleeding risk. Further studies are needed to implement the use of DAPT in real-world PCI.

Comparison of pulse contour analysis by Pulsioflex and Vigileo to measure and track changes of cardiac output in critically ill patients.

BACKGROUND: We compared the new Pulsioflex and the Vigileo devices to measure cardiac index (CI) in critically ill patients. Both devices measure CI by pulse-contour analysis. The Pulsioflex device also allows an auto-calibration (not based on thermodilution). METHODS: Patients were included if we administered fluids (20 patients), reduced (20 patients), or increased (20 patients) the dose of norepinephrine. Before and after interventions, we measured CI provided by the Vigileo (CIVig) and Pulsioflex (CIPfx) devices before and after its auto-calibration. CI measured by transpulmonary thermodilution (CIthermo) was used as the reference. RESULTS: Considering absolute values of CI (n=120), the percentage error was 59% for CIVig vs CIthermo and 40% for CIthermo vs CIPfx. Auto-calibrating CIPfx after interventions did not improve the percentage error between CIPfx and CIthermo (39%). Considering the fluid-induced changes in CI, the coefficient of correlation with changes in CIthermo was 0.50 for CIVig, and 0.73 for CIPfx (P=0.27). It was not significantly improved if CIPfx was auto-calibrated (r=0.64). Considering the norepinephrine-induced changes in CI, the coefficient of correlation with changes in CIthermo was 0.41 for CIVig. It tended to be better for CIPfx (r=0.71, P=0.07). It was not significantly improved by auto-calibration (r=0.53). CONCLUSIONS: The Pulsioflex did not reliably estimate the absolute values of CI. For tracking fluid-induced changes in CI, the Pulsioflex was reliable, and also the Vigileo. For tracking norepinephrine-induced changes in CI, it was also reliable and tended to be better than the Vigileo. Auto-calibration allowed by the system did not improve its reliability.

Non-pneumatic anti-shock garment for improving maternal survival following severe postpartum haemorrhage: a systematic review.

INTRODUCTION: Women with postpartum haemorrhage (PPH) in developing countries often present in critical condition when treatment might be insufficient to save lives. Few studies have shown that application of non-pneumatic anti-shock garment (NASG) could improve maternal survival. METHODS: A systematic review of the literature explored the effect of NASG use compared with standard care for treating PPH. Medline, EMBASE and PubMed were searched. Methodological quality was assessed following the criteria suggested by the Cochrane Effective Practice and Organization of Care Group. Guidelines on Meta-analysis of Observational Studies in Epidemiology were used for reporting the results. Mantel-Haenszel methods for meta-analysis of risk ratios were used. RESULTS: Six out 31 studies met the inclusion criteria; only one cluster randomized controlled trial (c-RCT). Among observational studies, NASG fared better than standard care regarding maternal mortality reduction (Relative Risk (RR) 0.52 (95% Confidence interval (CI) 0.36 to 0.77)). A non-significant reduction of maternal mortality risk was observed in the c-RCT (RR: 0.43 (95% CI: 0.14 to 1.33)). No difference was observed between NASG use and standard care on use of blood products. Severe maternal outcomes were used as proxy for maternal death with similar pattern corroborating the trend towards beneficial effects associated with NASG. CONCLUSION: NASG is a temporizing alternative measure in PPH management that shows a trend to reduce PPH-related deaths and severe morbidities. In settings where delays in PPH management are common, particularly where constraints to offer blood products and definitive treatment exist, use of NASG is an intervention that should be considered as a policy option while the standard conditions for care are being optimized.

Pathological Substratum for a Case of Fulminant Myocarditis Treated with Extracorporeal Membrane Oxygenation and Subsequent Heart Transplantation.

Fulminant myocarditis has been defined as the clinical manifestation of cardiac inflammation with rapid-onset heart failure and cardiogenic shock. We report on the case of a 23-yr-old woman with pathology-proven fulminant lymphocytic myocarditis presenting shock with elevated cardiac troponin I and ST segments in V1-2, following sustained ventricular tachycardia and a complete atrioventricular block. About 55 min of intensive cardio-pulmonary resuscitation, with extracorporeal membrane oxygenation support, bridged the patient to orthotopic heart transplantation. The explanted heart revealed diffuse lymphocytic infiltration and myocyte necrosis in all four cardiac chamber walls. Aggressive mechanical circulatory support may be an essential bridge for recovery or even transplantation in patients with fulminant myocarditis with shock.

Post-paracentesis circulatory derangements are related to monocyte activation.

BACKGROUND & AIMS: Post-paracentesis circulatory dysfunction is associated with development of hepatorenal syndrome and increased mortality. The impact of large volume paracentesis (LVP) on the 24-h blood pressure (BP) profile is unknown, and the relationship to Na+-retentive and pro-inflammatory cytokines also remains unknown. The aims of this study were to (i) define the effects of LVP with albumin administration on 24-h BP profiles, and (ii) relate changes in BP over time to changes in Na+-retentive hormones, clinical factors and inflammatory cytokines. METHODS: Ten patients undergoing LVP had 24-h ambulatory BP monitoring performed pre- and post-paracentesis. Markers of the innate immune system, bacterial translocation and Na+-retentive hormones were drawn pre- and post-LVP. RESULTS: Mean arterial pressure (MAP) dropped in nine of the 10 patients in the 24 h following a paracentesis compared to 24 h preceding the procedure (mean drop of 5.5 mmHg, P<0.005). A mixed effects model was used to define time-covariate interactions in predicting changes in BP profile. Monocyte chemotactic protein-1 (MCP1) was associated with Δsystolic BP (ß=-0.011, P<0.05), Δdiastolic BP (ß=-0.012, P<0.05) and ΔMAP (ß=-0.012, P<0.05). Plasma renin activity was also significantly associated with Δsystolic BP (ß=-0.21, P<0.05). Renal function was also significantly reduced following LVP. CONCLUSIONS: Systolic, diastolic and MAP decreased over 24 h after LVP compared to the 24 h pre-LVP. This drop is related to increases in MCP-1 after LVP. Increased MCP-1, a marker of monocyte activation, was strongly related to changes in BP.

An evidence-based prehospital guideline for external hemorrhage control: American College of Surgeons Committee on Trauma.

This report describes the development of an evidence-based guideline for external hemorrhage control in the prehospital setting. This project included a systematic review of the literature regarding the use of tourniquets and hemostatic agents for management of life-threatening extremity and junctional hemorrhage. Using the GRADE methodology to define the key clinical questions, an expert panel then reviewed the results of the literature review, established the quality of the evidence and made recommendations for EMS care. A clinical care guideline is proposed for adoption by EMS systems. Key words: tourniquet; hemostatic agents; external hemorrhage.

Resuscitative goals and new strategies in severe trauma patient resuscitation.

Traumatic injuries represent a major health problem all over the world. In recent years we have witnessed profound changes in the paradigm of severe trauma patient resuscitation, new concepts regarding acute coagulopathy in trauma have been proposed, and there has been an expansion of specific commercial products related to hemostasis, among other aspects. New strategies in severe trauma management include the early identification of those injuries that are life threatening and require surgical hemostasis, tolerance of moderate hypotension, rational intravascular volume replacement, prevention of hypothermia, correction of acidosis, optimization of oxygen carriers, and identification of those factors required by the patient (fresh frozen plasma, platelets, tranexamic acid, fibrinogen, cryoprecipitates and prothrombin complex). However, despite such advances, further evidence is required to improve survival rates in severe trauma patients.

Roles of peroxiredoxin II in the regulation of proinflammatory responses to LPS and protection against endotoxin-induced lethal shock.

Mammalian 2-Cys peroxiredoxin II (Prx II) is a cellular peroxidase that eliminates endogenous H(2)O(2). The involvement of Prx II in the regulation of lipopolysaccharide (LPS) signaling is poorly understood. In this report, we show that LPS induces substantially enhanced inflammatory events, which include the signaling molecules nuclear factor kappaB and mitogen-activated protein kinase (MAPK), in Prx II-deficient macrophages. This effect of LPS was mediated by the robust up-regulation of the reactive oxygen species (ROS)-generating nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and the phosphorylation of p47(phox). Furthermore, challenge with LPS induced greater sensitivity to LPS-induced lethal shock in Prx II-deficient mice than in wild-type mice. Intravenous injection of Prx II-deficient mice with the adenovirus-encoding Prx II gene significantly rescued mice from LPS-induced lethal shock as compared with the injection of a control virus. The administration of catalase mimicked the reversal effects of Prx II on LPS-induced inflammatory responses in Prx II-deficient cells, which suggests that intracellular H(2)O(2) is attributable, at least in part, to the enhanced sensitivity to LPS. These results indicate that Prx II is an essential negative regulator of LPS-induced inflammatory signaling through modulation of ROS synthesis via NADPH oxidase activities and, therefore, is crucial for the prevention of excessive host responses to microbial products.

Melanocortins as potential therapeutic agents in severe hypoxic conditions.

Melanocortin peptides with the adrenocorticotropin/melanocyte-stimulating hormone (ACTH/MSH) sequences and synthetic analogs have protective and life-saving effects in experimental conditions of circulatory shock, myocardial ischemia, ischemic stroke, traumatic brain injury, respiratory arrest, renal ischemia, intestinal ischemia and testicular ischemia, as well as in experimental heart transplantation. Moreover, melanocortins improve functional recovery and stimulate neurogenesis in experimental models of cerebral ischemia. These beneficial effects of ACTH/MSH-like peptides are mostly mediated by brain melanocortin MC(3)/MC(4) receptors, whose activation triggers protective pathways that counteract the main ischemia/reperfusion-related mechanisms of damage. Induction of signaling pathways and other molecular regulators of neural stem/progenitor cell proliferation, differentiation and integration seems to be the key mechanism of neurogenesis stimulation. Synthesis of stable and highly selective agonists at MC(3) and MC(4) receptors could provide the potential for development of a new class of drugs for a novel approach to management of severe ischemic diseases.

Predicting haemorrhage in pre-hospital traumatic patients: evaluation of the novel heart-to-arm time index.

BACKGROUND: Early recognition of hypovolaemia in trauma patients is very important. However, the most often used clinical signs, such as hypotension and tachycardia, lack specificity and sensitivity. METHODS: We propose a non-invasive index of hypovolaemia, the heart to arm time (iHAT), based on a modified pulse transit time indexed to heart rate. Pulse transit time is the sum of pre-ejection period and vascular transit time. Following pre-load reductions due to hypovolaemia, ventricular diastolic filling time increases causing an increase in pre-ejection-period, pulse transit time, and hence iHAT. One hundred and four consecutive patients with suspected major trauma were enrolled. The primary aim was to evaluate the use of the iHAT for detecting haemorrhage in major trauma. The secondary end point was to compare the specificity and sensitivity of iHAT compared to commonly used indexes. RESULTS: iHAT was calculated in 84 subjects, 11 of whom were haemorrhagic. iHAT discriminated haemorrhagic from non-haemorrhagic group (46.8% vs. 66.9%, P < 0.0001). The cut-off for iHAT with the best compromise between sensitivity (90.9%) and specificity (100%) was reached at the 58.78% level. Comparing haemorrhagic and non-haemorrhagic patients, the area under the ROC curve was 0.952 for iHAT, 0.835 for heart rate, and 0.911 for systolic blood pressure, showing no significant differences. CONCLUSIONS: iHAT is a non-invasive index that can identify haemorrhage in trauma patients with high sensitivity and specificity. These data should be considered as an exploration, but any conclusion should be validated in a new set of consecutive patients.

Methylxanthines inhibit late-onset circulatory collapse in preterm infants.

BACKGROUND: Several drugs, when used chronically in very preterm infants, are considered to be associated with the development of late-onset circulatory collapse (LCC), which can lead to neurodevelopmental impairment. Despite its clinical importance, conclusive risk factors for LCC have yet to be identified. The aim of the present study was to investigate the relationship between LCC and diuretics, methylxanthines, levothyroxine, and sodium chloride. METHODS: Infants born at <28 weeks gestational age were enrolled and divided into two groups: the LCC group and the non-LCC group. Use of diuretics, methylxanthines, or levothyroxine, and the sodium intake in each infant were recorded. We then determined if these represented primary risk factors associated with the development of LCC, using multivariate analysis to exclude confounding factors. RESULTS: Thirty-seven preterm infants were eligible for this study. LCC developed in 10 infants; 27 infants did not develop the disease. Only methylxanthine was significantly associated with a decrease in the incidence of LCC (odds ratio, 0.04; P < 0.05). We also observed a significant positive correlation between sodium intake and the period from diuretic treatment to LCC onset. CONCLUSIONS: Methylxanthine use was significantly associated with LCC onset. Diuretics may have the ability to provoke LCC through sodium wasting, resulting in a negative balance of the electrolyte. The incidence of LCC could be lowered by paying particular attention to infants' sodium balance, and by aggressive methylxanthine treatment.