Peritoneal Dialysis in Dengue Shock Syndrome May Be Detrimental

Dengue shock syndrome is the most severe form of Dengue that can be fatal. Nonresponders to standard therapy need intensive care. This paper outlines the clinical features, complications, and outcomes of Dengue Shock Syndrome not responding to standard therapies and needing supportive care in a tertiary referral intensive care unit of a developing country. Nearly one-third die within 3 days of admission to ICU. Peritoneal dialysis predicts the worst outcomes

Oxygen Delivery and Oxygen Consumption in Pediatric Fluid Refractory Septic Shock During the First 42 h of Therapy and Their Relationship to 28-Day Outcome

Background: In septic shock, both oxygen delivery (DO2) and oxygen consumption (VO2) are dysfunctional. The current therapeutic regimens are geared to normalize global oxygen delivery (DO2) to tissues via goal directed therapies but mortality remains high at 10–20%.Methods: We studied cardiac index (CI), systemic vascular resistance index (SVRI), central venous oxygen saturation (ScvO2), central venous pressure (CVP), peripheral oxygen saturation (SpO2), mean blood pressure (MBP), body temperature, blood lactate, base excess and hemoglobin concentration (Hb) in a cohort of children admitted in “fluid-refractory” severe septic shock to pediatric intensive care, over 4.5-years. We calculated their 6 h global oxygen delivery (DO2) and global oxygen consumption (VO2) over the first 42 h and looked at factors associated with VO2/DO2 ratio (i.e., global oxygen extraction, gO2ER) and 28-day mortality.Results: Sixty-two children mean age (SD) 7.19 (5.44) years were studied. Fifty-seven (93%) children were sedated and mechanically ventilated and all received adrenaline or noradrenaline or both and added milrinone in 6 (9.6%). At 28 days, 9 (14.5%) were dead. The global oxygen extraction ratio (gO2ER) was consistently lower amongst the survivors and independently predicted mortality (ROC AUC = 0.75). A lactate level of 4 mmol/l or above, when associated with a concurrent metabolic acidosis predicted mortality with a sensitivity of 100% (95% CI 90.5–100) and a specificity of 67.7% (95% CI 62.2–72.9). A gO2ER of 0.48 or above on admission to the PICU was associated with death with a 66.7% sensitivity (95%CI 29.9–92.5) and 90.5% specificity (95%CI 79.3–96.8). A global O2ER of >0.48 combined with a concurrent blood lactate >4.0 mmol/l at any time within the first 42 h of therapy predicted death with a sensitivity of 63.9% (95% CI, 46.2–79.1) and specificity of 97.8% (95% CI, 95.7–99.0). A radar plot identified MBP-CVP difference, and CI as additional goals of therapy that may offer a survival benefit.Conclusions: Global O2ER of >0.48 with a concurrent blood lactate >4.0 mmol/l in children with metabolic acidosis was an independent factor associated with death in fluid resistant septic shock. Trends of gO2ER seem useful to recognize survivors and non-survivors early in the illness

Clinical Study Peritoneal Dialysis in Dengue Shock Syndrome May Be Detrimental

Dengue shock syndrome is the most severe form of Dengue that can be fatal. Nonresponders to standard therapy need intensive care. This paper outlines the clinical features, complications, and outcomes of Dengue Shock Syndrome not responding to standard therapies and needing supportive care in a tertiary referral intensive care unit of a developing country. Nearly one-third die within 3 days of admission to ICU. Peritoneal dialysis predicts the worst outcomes

A Students’ Perspective on University Education and Well-Being One-Year into the COVID-19 Pandemic

We report university student perspectives on COVID-19 impact on education, general health and well-being, one year into the pandemic.   A ‘low risk’ questionnaire with modified General Health (GHQ-28) and Anxiety Disorder (GAD-7) instruments was shared with students via an email link over a 4-week period.   725 students responded from five countries. Half of the students reported significant general health difficulties and more than ten per cent experienced a severe state of generalised anxiety disorder. The virtual learning techniques adopted during the pandemic were welcomed by students but many were frustrated by the poor quality teaching material, poor scheduling of virtual sessions with inadequate spacing and assessments not being truly representative of what was taught. Digital poverty due to inadequacies in hardware, software compatibility and connectivity were major hindrances to virtual learning.   Universities should urgently modify the virtual training methods and enhance mental health and wellbeing support before disaster strikes

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

The role of nitric oxide in childhood hypertension and a critical analysis of the measurement and interpretation of blood pressure

Nitric oxide, synthesised continuously from the amino acid L-arginine by the constitutive nitric oxide synthase enzyme of the vascular endothelium maintains a constant vasodilator tone. This basal release of nitric oxide, that help maintains blood pressure at normal level, was believed to be diminished in adults with essential (primary) hypertension but no data was available on its role in childhood hypertension. Raised plasma levels of naturally occurring nitric oxide synthase inhibitors (arginine analogues) had been identified in some cases of pregnancy induced hypertension and in renal failure but their physiological importance was uncertain. Experimentally, however, oral administration of nitric oxide inhibitors was known to produce hypertension. The initial investigations described in Part A of this thesis demonstrate raised plasma levels of arginine analogues, particularly asymmetric dimethyl arginine (ADMA) in children with hypertension. Subsequent experiments in vitro on mice aortic rings confirm that the concentrations of ADMA detected in human plasma may be sufficient to cause an alteration in vascular tone, hence blood pressure. Although a concomitant reduction in nitric oxide generation was expected in these subjects, its assessment indirectly by estimating plasma levels of nitrate appear to suggest otherwise. Additionally higher levels of plasma ADMA was associated with a lower plasma renin activity in these subjects, a possible but hitherto unknown negative feed back mechanism for renin dependent blood pressure control. Furthermore, raised levels of ADMA were shown to be associated with raised plasma levels of the adhesion molecule VCAM-1, a known intermediary in the development of atheroma. This may have wider implications in terms of the development of atheroma in other conditions with raised plasma arginine analogues. Despite the known influence of these plasma agents on blood pressure, none correlated with blood pressure itself in these subjects. On investigation of this observation, a second theme evolved; i.e. factors causing errors in interpretation of blood pressure and its measurement. This is described in Part B that includes a critical analysis of current approved methods of blood pressure measurement and clinical validation of new blood pressure monitors for use in children. This thesis therefore provides the first insight into the role of nitric oxide, in particular its inhibitor ADMA in childhood hypertension especially in the presence of renal impairment. This molecule is at least likely to be involved in modulation of renin angiotensin system and endothelium mediated complications such as atheroma in hypertensive children, besides its prominent role in altering vascular tone and natriuresis. Demonstration of a link between ADMA and blood pressure itself in vivo, however, is difficult due to the complexity of the cardiovascular regulation and covert errors in blood pressure measurement and interpretation