Total serum cortisol level is low in children with severe dengue shock syndrome.

Dengue shock syndrome (DSS) is a potentially critical and life-threatening concern, especially in children of tropical countries. The serum cortisol levels in severe DSS or later stages of DSS are limited references. We prospectively studied an association between of serum cortisol as well as interleukin levels and the severity of DSS in pediatric patients. A prospective cross-sectional study of 35 consecutive DSS cases (3 months to 16 years old) admitted to our institution from July 1, 2019, to June 30, 2020 was conducted. Serum cortisol, IL-6, and IL-10 were measured at T0 (shock recognition) and T12 (12 hours after T0); their values were presented as median and interquartile ranges (25%-75%). Severe DSS included patients with impalpable pulses or systolic blood pressure < 70 mmHg, recurrent shock, and prolonged shock. In contrast, non-severe DSS presented circulatory failure without any features of severe DSS. A total of 8 (22.8%) severe DSS patients expressed the cortisol (T0) significantly lower compared to the non-severe DSS group (7.3 µg/dl versus 14.3 µg/dl, p=0.008). In severe DSS, there was a minimal change in cortisol levels between T0 and T12 (7.3 µg/dl and 4.7 µg/dl p>0.05), whereas the decrease is significant in their counterparts (14.3 µg/dl to 5.6 µg/dl, p<0.005). Additionally, there were moderate correlations between IL-6 (T0), IL-10 (T0), IL-10 (T12) and total fluid requirement (Spearman's rho = 0.47, 0.4, and 0.36, respectively; p<0.05). Our study demonstrated that adrenal dysfunction was present in patients with severe and non-severe DSS, as noted by cortisol level at T12. In addition, IL-6 and IL-10 levels are correlated with the total fluid requirement, which is a marker of DSS severity. Further studies could reveal how adrenal dysfunction in pediatric patients with DSS can affect outcomes and the potential roles of interleukin levels in fluid management strategy.

Coronavirus disease 2019 (COVID-19): A systematic review of 133 Children that presented with Kawasaki-like multisystem inflammatory syndrome.

Kawasaki-like disease (KLD) and multisystem inflammatory syndrome in children (MIS-C) are considered as challenges for pediatric patients under the age of 18 infected with coronavirus disease 2019 (COVID-19). A systematic search was performed on July 2, 2020, and updated on December 1, 2020, to identify studies on KLD/MIS-C associated with COVID-19. The databases of Scopus, PubMed, Web of Science, Embase, and Scholar were searched. The hospitalized children with a presentation of Kawasaki disease (KD), KLD, MIS-C, or inflammatory shock syndromes were included. A total number of 133 children in 45 studies were reviewed. A total of 74 (55.6%) cases had been admitted to pediatric intensive care units (PICUs). Also, 49 (36.8%) patients had required respiratory support, of whom 31 (23.3%) cases had required mechanical ventilation/intubation, 18 (13.5%) cases had required other oxygen therapies. In total, 79 (59.4%) cases had been discharged from hospitals, 3 (2.2%) had been readmitted, 9 (6.7%) had been hospitalized at the time of the study, and 9 (6.7%) patients had expired due to the severe heart failure, shock, brain infarction. Similar outcomes had not been reported in other patients. Approximately two-thirds of the children with KLD associated with COVID-19 had been admitted to PICUs, around one-fourth of them had required mechanical ventilation/intubation, and even some of them had been required readmissions. Therefore, physicians are strongly recommended to monitor children that present with the characteristics of KD during the pandemic as they can be the dominant manifestations in children with COVID-19.

Multisystem outcomes and predictors of mortality in critically ill patients with COVID-19: Demographics and disease acuity matter more than comorbidities or treatment modalities.

BACKGROUND: We sought to describe characteristics, multisystem outcomes, and predictors of mortality of the critically ill COVID-19 patients in the largest hospital in Massachusetts. METHODS: This is a prospective cohort study. All patients admitted to the intensive care unit (ICU) with reverse-transcriptase-polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection between March 14, 2020, and April 28, 2020, were included; hospital and multisystem outcomes were evaluated. Data were collected from electronic records. Acute respiratory distress syndrome (ARDS) was defined as PaO2/FiO2 ratio of ≤300 during admission and bilateral radiographic pulmonary opacities. Multivariable logistic regression analyses adjusting for available confounders were performed to identify predictors of mortality. RESULTS: A total of 235 patients were included. The median (interquartile range [IQR]) Sequential Organ Failure Assessment score was 5 (3-8), and the median (IQR) PaO2/FiO2 was 208 (146-300) with 86.4% of patients meeting criteria for ARDS. The median (IQR) follow-up was 92 (86-99) days, and the median ICU length of stay was 16 (8-25) days; 62.1% of patients were proned, 49.8% required neuromuscular blockade, and 3.4% required extracorporeal membrane oxygenation. The most common complications were shock (88.9%), acute kidney injury (AKI) (69.8%), secondary bacterial pneumonia (70.6%), and pressure ulcers (51.1%). As of July 8, 2020, 175 patients (74.5%) were discharged alive (61.7% to skilled nursing or rehabilitation facility), 58 (24.7%) died in the hospital, and only 2 patients were still hospitalized, but out of the ICU. Age (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.04-1.12), higher median Sequential Organ Failure Assessment score at ICU admission (OR, 1.24; 95% CI, 1.06-1.43), elevated creatine kinase of ≥1,000 U/L at hospital admission (OR, 6.64; 95% CI, 1.51-29.17), and severe ARDS (OR, 5.24; 95% CI, 1.18-23.29) independently predicted hospital mortality.Comorbidities, steroids, and hydroxychloroquine treatment did not predict mortality. CONCLUSION: We present here the outcomes of critically ill patients with COVID-19. Age, acuity of disease, and severe ARDS predicted mortality rather than comorbidities. LEVEL OF EVIDENCE: Prognostic, level III.

Characteristics, Outcomes, and Trends of Patients With COVID-19-Related Critical Illness at a Learning Health System in the United States.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. OBJECTIVE: To describe the epidemiology of COVID-19-related critical illness, including trends in outcomes and care delivery. DESIGN: Single-health system, multihospital retrospective cohort study. SETTING: 5 hospitals within the University of Pennsylvania Health System. PATIENTS: Adults with COVID-19-related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. MEASUREMENTS: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. RESULTS: Among 468 patients with COVID-19-related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. LIMITATIONS: Single-health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications. CONCLUSION: Among patients with COVID-19-related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Shock and Myocardial Injury in Children With Multisystem Inflammatory Syndrome Associated With SARS-CoV-2 Infection: What We Know. Case Series and Review of the Literature.

BACKGROUND: Multisystem inflammatory syndrome associated with SARS-CoV-2 infection can lead to myocardial injury and shock in children, likely the result of a severe inflammatory state, and can mimic Kawasaki disease. OBJECTIVE: To describe the characteristics of shock and myocardial injury in children with confirmed or suspeted COVID-19 during the SARS-CoV-2 pandemic in Spain, including clinical presentation, laboratory and imaging findings, treatment, disease course, and outcome. An extensive literature review is provided. METHODS: Retrospective case series including all children (age 1 month-18 years) admitted to a pediatric intensive care unit in Madrid, Spain, between March 15 and April 30, 2020 with suspected or confirmed SARS-CoV-2 infection and shock. RESULTS: Twelve previously healthy patients with shock, age 5 to 14 years, were included. All required volume resuscitation and 75% required vasoactive/inotropic support. Distributive shock was present on admission in 67% (n = 8), and 4 patients (33%) showed features of cardiogenic shock. Myocardial injury was diagnosed in 67% (n = 8) and ventricular dysfunction in 33% (n = 4). The most common symptoms on presentation were fever (100%), anorexia (100%), diarrhea (75%), and vomiting (75%). Five patients showed signs of Kawasaki disease but none met the criteria for the classic form. Laboratory findings revealed lymphopenia (83%), thrombocytopenia (83%), and increased inflammatory markers (100%). Respiratory status was not significantly impacted. Chest X-ray showed bilateral alveolar infiltrates in 7 (58%) and bilateral pneumonia in 3 (25%). COVID-19 was confirmed in 11 cases (92%). All received empirical therapy against COVID-19, thromboprophylaxis and immunomodulation. Median stay in the PICU and inpatient ward was 4.5 and 10 days, respectively. No patients died. CONCLUSION: Multisystem inflammatory syndrome in children with COVID-19 can mimic Kawasaki disease and lead to a combination of distributive and cardiogenic shock, probably secondary to a hyperinflammatory state that remains to be precisely defined. Treatment strategies include hemodynamic support, empirical therapies against COVID-19, thromboprophylaxis, and immunomodulation.

Angiotensin II Administration in Patients With COVID-19 Shock.

PURPOSE: To understand the hemodynamic effect of angiotensin II as a vasopressor in patients with shock secondary to COVID-19 infection. METHODS: A retrospective analysis was performed on all patients at a single center with COVID-19 infection and shock who were treated with angiotensin II. The hemodynamic response to angiotensin II was estimated by recording the mean arterial pressure, norepinephrine equivalent dose (NED) and urine output. RESULTS: Ten patients with COVID-19 related shock were treated with angiotensin II. Over the initial 6 hours, the average the NED decreased by 30.4% (from 64.6 to 44 µg/min) without a significant change in the mean arterial pressure (0.7% decrease). Six patients experienced at least a 25% reduction in NED by 6 hours, and 2 experienced at least a 50% reduction. CONCLUSIONS: On average, the hemodynamic response to angiotensin II in COVID-19 related shock was favorable. Two patients had a marked rapid improvement. Given the relationship of SARS-CoV-2 with the renin-angiotensin-aldosterone system, further evaluation of angiotensin II for the treatment of COVID-19 related shock is warranted.

Recomendación para la sospecha, manejo y seguimiento del compromiso cardiovascular en pacientes con Síndrome Inflamatorio Multisistémico en Pediatría asociado a COVID-19 (PIMS-TC). Declaración de Posición de la Sociedad Chilena de Pediatría (SOCHIPE) y Sociedad Chilena de Cardiología y Cirugía Cardiovascular (SOCHICAR) / Recommendation for the recognition, management and follow up of cardiovascular compromise in patients with Pediatric Multisystemic Inflammatory Syndrome associated with COVID-19 (PIMS-CT). Position statement of Chilean Scientific Societies

Desde la aparición de la pandemia por SARS-CoV-2, la población pediátrica ha sido menos afectada por la enfermedad tanto en frecuencia como en severidad. Sin embargo, desde abril de este año se han reportado casos de presentación y gravedad variables, caracterizados por fenómenos inflamato rios que afectan múltiples órganos, condición denominada Síndrome Inflamatorio Multisistémico Pediátrico (PIMS). La literatura describe frecuente compromiso cardíaco, hasta en un 80%. Este se caracteriza por injuria miocárdica con significativa elevación de biomarcadores: Troponinas séricas I/T, BNP o NT-ProBNP, unido a diversos grados de disfunción ventricular, pericarditis, valvulitis y arritmias. Además, se ha evidenciado la presencia de compromiso coronario el cual puede ocurrir hasta en un 23% de los casos, en un rango que va desde dilataciones hasta aneurismas. El seguimien to cardiológico hospitalizado y ambulatorio se ha sistematizado en base a los fenotipos clínicos de presentación: injuria miocárdica (miocarditis, valvulitis, pericarditis), shock (habitualmente de tipo "vasopléjico"), manifestaciones tipo Enfermedad de Kawasaki y aquellos casos PIMS que no cumplen con la clínica de los tres precedentes. Este último grupo es el que representa el mayor desafío en el cor to, mediano y seguimiento a largo plazo. Por esta razón se requiere un equipo multidisciplinario para su manejo. Considerando la alta frecuencia del compromiso cardíaco en el PIMS y la importancia de lograr un consenso en su manejo y seguimiento, se presentan estas recomendaciones según el estado actual del conocimiento de esta patología recientemente descrita.

Since the onset of the SARS-CoV-2 pandemic, the pediatric population has been less affected by the disease both in frequency and severity. However, since April cases of variable presentation and severity characterized by inflammatory phenomena that affect multiple organs have been reported, a condition called Multisystem Inflammatory Syndrome in Children (MIS-C). The literature has reported frequent cardiac involvement, up to 80%. This is characterized by myocardial injury with a significant increase of biomarkers such as serum troponins I and T, BNP, or NT-ProBNP coupled with varying degrees of ventricular dysfunction, pericarditis, valvulitis, and arrhythmias. Coronary compromise has also been described, which can occur in up to 23% of cases, and ranges from dila tations to aneurysms. Inpatient and outpatient cardiology follow-up has been systematized based on the clinical phenotypes such as myocardial injury (myocarditis, valvulitis, pericarditis), shock (usua lly vasoplegic), Kawasaki disease-type manifestations, and those MIS-C that do not comply with the clinic of the previous three. This last group represents the main challenge in the short-, medium- and long-term follow-up, therefore, it is necessary a multidisciplinary team for managing these patients. Considering the high frequency of cardiac compromise in MIS-C, and the importance of reaching a consensus regarding its management and follow-up, we present these recommendations according to the current state of knowledge regarding this recently described pathology.

[Recommendation for the recognition, management and follow up of cardiovascular compromise in patients with Pediatric Multisystemic Inflammatory Syndrome associated with COVID-19 (PIMS-CT). Position statement of Chilean Scientific Societies]. / Recomendación para la sospecha, manejo y seguimiento del compromiso cardiovascular en pacientes con Síndrome Inflamatorio Multisistémico en Pediatría asociado a COVID-19 (PIMS-TC). Declaración de Posición de la Sociedad Chilena de Pediatría (SOCHIPE) y Sociedad Chilena de Cardiología y Cirugía Cardiovascular (SOCHICAR).

Since the onset of the SARS-CoV-2 pandemic, the pediatric population has been less affected by the disease both in frequency and severity. However, since April cases of variable presentation and severity characterized by inflammatory phenomena that affect multiple organs have been reported, a condition called Multisystem Inflammatory Syndrome in Children (MIS-C). The literature has reported frequent cardiac involvement, up to 80%. This is characterized by myocardial injury with a significant increase of biomarkers such as serum troponins I and T, BNP, or NT-ProBNP coupled with varying degrees of ventricular dysfunction, pericarditis, valvulitis, and arrhythmias. Coronary compromise has also been described, which can occur in up to 23% of cases, and ranges from dila tations to aneurysms. Inpatient and outpatient cardiology follow-up has been systematized based on the clinical phenotypes such as myocardial injury (myocarditis, valvulitis, pericarditis), shock (usua lly vasoplegic), Kawasaki disease-type manifestations, and those MIS-C that do not comply with the clinic of the previous three. This last group represents the main challenge in the short-, medium- and long-term follow-up, therefore, it is necessary a multidisciplinary team for managing these patients. Considering the high frequency of cardiac compromise in MIS-C, and the importance of reaching a consensus regarding its management and follow-up, we present these recommendations according to the current state of knowledge regarding this recently described pathology.

Dengue virus-elicited tryptase induces endothelial permeability and shock.

Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and organs. Mast cells (MCs), which line blood vessels and regulate vascular function, are able to detect DENV in vivo and promote vascular leakage. Here, we identified that a MC-derived protease, tryptase, is consequential for promoting vascular permeability during DENV infection, through inducing breakdown of endothelial cell tight junctions. Injected tryptase alone was sufficient to induce plasma loss from the circulation and hypovolemic shock in animals. A potent tryptase inhibitor, nafamostat mesylate, blocked DENV-induced vascular leakage in vivo. Importantly, in two independent human dengue cohorts, tryptase levels correlated with the grade of DHF severity. This study defines an immune mechanism by which DENV can induce vascular pathology and shock.

Kawasaki disease triggered by parvovirus infection: an atypical case report of two siblings.

BACKGROUND: There are reports of the familial occurrence of Kawasaki disease but only a few reports described Kawasaki disease in siblings. However, the familial cases were not simultaneous. In these patients the idea of infective agents as trigger must be considered. CASE PRESENTATION: We describe two siblings with atypical presentations of Kawasaki disease; the sister was first diagnosed as having parvovirus infection with anemia and the brother was diagnosed as having myocarditis. The first patient was a 9-month-old Caucasian girl with fever, conjunctivitis, rash, and pharyngitis, and later she had cervical adenopathy, diarrhea and vomiting, leukocytosis, and anemia, which were explained by positive immunoglobulin M against parvovirus. However, coronary artery lesions with aneurysms were documented at day 26 after fever onset. An infusion of intravenous immunoglobulin and high doses of steroids were not efficacious to resolve the coronary lesions. She was treated with anakinra, despite a laboratory test not showing inflammation, with prompt and progressive improvement of coronary lesions. Her 7-year-old Caucasian brother presented vomiting and fever at the same time as she was unwell, which spontaneously resolved after 4 days. Four days later, he again presented with fever with abdominal pain, associated with tachypnea, stasis at the pulmonary bases, tachycardia, gallop rhythm, hypotension, secondary anuria, and hepatomegaly. An echocardiogram revealed a severe hypokinesia, with a severe reduction of the ejection fraction (20%). He had an increase of immunoglobulin M anti-parvovirus, tested for the index case of his sister, confirming the suspicion of viral myocarditis. He received dopamine, dobutamine, furosemide plus steroids, with a progressive increase of the ejection fraction to 50%. However, evaluating his sister's history, the brother showed a myocardial dysfunction secondary to Kawasaki shock syndrome. CONCLUSIONS: We report on familial Kawasaki disease in two siblings which had the same infectious trigger (a documented parvovirus infection). The brother was diagnosed as having post-viral myocarditis. However, in view of the two different and simultaneous evolutions, the girl showed Kawasaki disease with late coronary artery lesions and aneurysms, whereas the brother showed Kawasaki shock syndrome with myocardial dysfunction. We stress the effectiveness of anakinra in non-responder Kawasaki disease and the efficacy on coronary aneurysms.

Correlations between clinical features and death in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging high-fatality infectious disease caused by a novel phlebovirus belonging to the Bunyaviridae family. Thus, the independent predictors of death in this disease must be identified to improve the survival of affected patients.A total of 25 hospitalized patients with SFTS virus infection were enrolled in our study, and their medical records and laboratory data were reviewed. The risk factors for death were examined by binary logistic regression.The patient age was significantly higher in the deceased cases than in those who recovered (P = .020). Moreover, the occurrence of shock, respiratory failure, hemorrhagic manifestations, kidney dysfunction, and arrhythmia was significantly more common in the deceased cases than in the recovered cases (P = .016, P = .004, P = .005, P = .002, P = .038). Univariate binary logistic regression showed that shock, arrhythmia, and hemorrhage, as well as PCT, serum creatinine (Scr), and blood urea nitrogen (BUN) elevations, were the risk factors for death (odds ratio, OR 28.5, P = .015; OR 13.5, P = .027; OR 36, P = .008; OR 28.5, P = .015; OR 36, P = .008; and OR 76.0, P = .004). However, the BUN increase was the only independent risk factor for death indicated by multivariate logistic regression (OR 76.0, P = .004).SFTS presents with a high fatality rate. When patients with SFTS manifest shock, arrhythmia, hemorrhage, PCT increase, and Scr and BUN elevations, especially BUN > 8.2 µmol/L, health care providers should be alerted and must administer early intervention to prevent the progress to death.

Cardio-haemodynamic assessment and venous lactate in severe dengue: Relationship with recurrent shock and respiratory distress.

BACKGROUND: Dengue can cause plasma leakage that may lead to dengue shock syndrome (DSS). In approximately 30% of DSS cases, recurrent episodes of shock occur. These patients have a higher risk of fluid overload, respiratory distress and poor outcomes. We investigated the association of echocardiographically-derived cardiac function and intravascular volume parameters plus lactate levels, with the outcomes of recurrent shock and respiratory distress in severe dengue. METHODS/PRINCIPLE FINDINGS: We performed a prospective observational study in Paediatric and adult ICU, at the Hospital for Tropical Diseases (HTD), Ho Chi Minh City, Vietnam. Patients with dengue were enrolled within 12 hours of admission to paediatric or adult ICU. A haemodynamic assessment and portable echocardiograms were carried out daily for 5 days from enrolment and all interventions recorded. 102 patients were enrolled; 22 patients did not develop DSS, 48 had a single episode of shock and 32 had recurrent shock. Patients with recurrent shock had a higher enrolment pulse than those with 1 episode or no shock (median: 114 vs. 100 vs. 100 b/min, P = 0.002), significantly lower Stroke Volume Index (SVI), (median: 21.6 vs. 22.8 vs. 26.8mls/m2, P<0.001) and higher lactate levels (4.2 vs. 2.9 vs. 2.2 mmol/l, P = 0.001). Higher SVI and worse left ventricular function (higher Left Myocardial Performance Index) on study days 3-5 was associated with the secondary endpoint of respiratory distress. There was an association between the total IV fluid administered during the ICU admission and respiratory distress (OR: 1.03, 95% CI 1.01-1.06, P = 0.001). Admission lactate levels predicted patients who subsequently developed recurrent shock (P = 0.004), and correlated positively with the total IV fluid volume received (rho: 0.323, P = 0.001) and also with admission ALT (rho: 0.764, P<0.001) and AST (rho: 0.773, P<0.001). CONCLUSIONS/SIGNIFICANCE: Echo-derived intravascular volume assessment and venous lactate levels can help identify dengue patients at high risk of recurrent shock and respiratory distress in ICU. These findings may serve to, not only assist in the management of DSS patients, but also these haemodynamic endpoints could be used in future dengue fluid intervention trials.

Hantavirus cardiopulmonary syndrome due to Puumala virus in Germany.

In Germany Puumala virus (PUUV), known to cause mild forms of hemorrhagic fever with renal syndrome (HFRS), is the predominating endemic hantavirus. We herein describe an unusually severe case of a PUUV infection that occurred in summer 2015 in South Eastern Germany in a region known to be endemic for PUUV since over ten years. A 54-year-old female gardener was admitted to hospital with fever, cough and dyspnea. Within 48hours the patient developed a rapid progressive adult respiratory distress syndrome (ARDS) with circulatory failure and required ECMO (extracorporeal membrane oxygenation) treatment. Serological and molecular biological examinations of serum samples confirmed an infection with PUUV. Partial sequences of the S- and M-segment clustered to a strain previously described in South Eastern Germany. Our reported case highlights, that in rare incidents PUUV can cause hantavirus cardiopulmonary syndrome, a syndrome that is usually found after infections with New World hantaviruses, and neurological symptoms.

Vascular leakage in dengue--clinical spectrum and influence of parenteral fluid therapy.

OBJECTIVE: Clinical management of dengue relies on careful monitoring of fluid balance combined with judicious intravenous (IV) fluid therapy. However, in patients with significant vascular leakage, IV fluids may aggravate serosal fluid accumulation and result in respiratory distress. METHODS: Trained physicians followed suspected dengue cases prospectively at seven hospitals across Asia and Latin America, using a comprehensive case report form that included daily clinical assessment and detailed documentation of parenteral fluid therapy. Applying Cox regression, we evaluated risk factors for the development of shock or respiratory distress with fluid accumulation. RESULTS: Most confirmed dengue patients (1524/1734, 88%) never experienced dengue shock syndrome (DSS). Among those with DSS, 176/210 (84%) had fluid accumulation, and in the majority (83%), this was detectable clinically. Among all cases with clinically detectable fluid accumulation, 179/447 (40%) were diagnosed with shock or respiratory distress. The risk for respiratory distress with fluid accumulation increased significantly as the infused volume over the preceding 24 h increased (hazard ratio 1.18 per 10 ml/kg increase; P < 0.001). Longer duration of IV therapy, use of a fluid bolus in the preceding 24 h, female gender and poor nutrition also constituted independent risk factors. CONCLUSIONS: Shock and respiratory distress are relatively rare manifestations of dengue, but some evidence of fluid accumulation is seen in around 50% of cases. IV fluids play a crucial role in management, but they must be administered with caution. Clinically and/or radiologically detectable fluid accumulations have potential as intermediate severity endpoints for therapeutic intervention trials and/or pathogenesis studies.

Dengue shock syndrome in an infant.

Dengue is a mosquito-borne infection affecting children and adults worldwide. In newborn infants, the dengue virus can cause diseases, especially in infants born to pregnant women hospitalised with dengue or postpartum women with fever. The authors report a case of a term newborn infant who presented with haemodynamic instability and thrombocytopaenia at the age of 7 days, without a history of clinical dengue infection in the mother. The physical examination revealed an afebrile and drowsy infant with a petechial rash all over the body and ecchymosis on both palms and soles. The authors confirmed the diagnosis using the dengue NS1 antigen on the first day of admission. The treatment included fluid management and platelet transfusion. The patient recovered well and was discharged from the hospital on the 10th day of hospitalisation.

Milrinone therapy for enterovirus 71-induced pulmonary edema and/or neurogenic shock in children: a randomized controlled trial.

OBJECTIVE: Enterovirus 71-induced brainstem encephalitis with pulmonary edema and/or neurogenic shock (stage 3B) is associated with rapid mortality in children. In a small pilot study, we found that milrinone reduced early mortality compared with historical controls. This prospective, randomized control trial was designed to provide more definitive evidence of the ability of milrinone to reduce the 1-week mortality of stage 3B enterovirus 71 infections. DESIGN: Prospective, unicenter, open-label, randomized, controlled study. SETTING: Inpatient ward of a large tertiary teaching hospital in Ho Chi Minh City, Vietnam. PATIENTS: Children (≤ 18 yr old) admitted with proven enterovirus 71-induced pulmonary edema and/or neurogenic shock. INTERVENTIONS: Patients were randomly assigned to receive intravenous milrinone (0.5 µg/kg/min) (n = 22) or conventional management (n = 19). Both groups received dopamine or dobutamine and intravenous immunoglobulin. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was 1-week mortality. The secondary endpoints included length of ventilator dependence and hospital stay and adverse events. The median age was 2 years with a predominance of boys in both groups. The 1-week mortality was significantly lower, 18.2% (4/22) in the milrinone compared with 57.9% (11/19) in the conventional management group (relative risk = 0.314 [95% CI, 0.12-0.83], p = 0.01). The median duration of ventilator-free days was longer in the milrinone treatment group (p = 0.01). There was no apparent neurologic sequela in the survivors in either group, and no drug-related adverse events were documented. CONCLUSIONS: Milrinone significantly reduced the 1-week mortality of enterovirus 71-induced pulmonary edema and/or neurogenic shock without adverse effects. Further studies are needed to determine whether milrinone might be useful to prevent progression of earlier stages of brainstem encephalitis.