Executive Summary: International Clinical Practice Guidelines for Pediatric Ventilator Liberation, A Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Document.

Rationale: Pediatric-specific ventilator liberation guidelines are lacking despite the many studies exploring elements of extubation readiness testing. The lack of clinical practice guidelines has led to significant and unnecessary variation in methods used to assess pediatric patients' readiness for extubation. Methods: Twenty-six international experts comprised a multiprofessional panel to establish pediatrics-specific ventilator liberation clinical practice guidelines, focusing on acutely hospitalized children receiving invasive mechanical ventilation for more than 24 hours. Eleven key questions were identified and first prioritized using the Modified Convergence of Opinion on Recommendations and Evidence. A systematic review was conducted for questions that did not meet an a priori threshold of ⩾80% agreement, with Grading of Recommendations, Assessment, Development, and Evaluation methodologies applied to develop the guidelines. The panel evaluated the evidence and drafted and voted on the recommendations. Measurements and Main Results: Three questions related to systematic screening using an extubation readiness testing bundle and a spontaneous breathing trial as part of the bundle met Modified Convergence of Opinion on Recommendations criteria of ⩾80% agreement. For the remaining eight questions, five systematic reviews yielded 12 recommendations related to the methods and duration of spontaneous breathing trials, measures of respiratory muscle strength, assessment of risk of postextubation upper airway obstruction and its prevention, use of postextubation noninvasive respiratory support, and sedation. Most recommendations were conditional and based on low to very low certainty of evidence. Conclusions: This clinical practice guideline provides a conceptual framework with evidence-based recommendations for best practices related to pediatric ventilator liberation.

Comparison of Blood Pressure Measurements by Currently Available Multiparameter Monitors and Mercury Column Sphygmomanometer in Patients Admitted in Pediatric Intensive Care Unit.

Background: The multiparameter monitor (MPM) is replacing mercury column sphygmomanometers (MCS) in acute care settings. However, data on the former's accuracy in critically ill children are scarce and mostly extrapolated from adults. We compared non-invasive blood pressure (NIBP) measurements by MPMs with MCS in pediatric intensive care unit (PICU). Patients: Adequately sedated and hemodynamically stabilized children (age, 1-144 months) were prospectively enrolled. Materials and methods: Three NIBP measurements were obtained from MCS (Diamond®, India) and MPM (Intellivue MX800® or Ultraview SL®) in rapid succession in the upper limb resting in supine position. Respective three measurements were averaged to obtain a paired set of NIBP readings, one each from MCS and MPM. Such readings were obtained thrice a day. NIBP readings were then compared, and agreement was assessed. Results: From 39 children [median age (IQR), 30 (10-72) months], 1,690 sets of NIBP readings were obtained. A-third of readings were from infants and children >96 months, while 383 (22.6%) readings were from patients on inotropes. Multiparameter monitors gave significantly higher NIBP readings compared to MCS [median systolic blood pressure (SBP), 6.5 (6.4-6.7 mm Hg); diastolic blood pressure (DBP), 4.5 (4.3-4.6 mm Hg); mean arterial pressure (MAP), 5.3 (5.1-5.4 mm Hg); p < 0.05]. It was consistent across age, gender, and critical care characteristics. Multiparameter monitors overestimated SBP in 80% of readings beyond the maximal clinically acceptable difference (MCAD). Conclusions: Non-invasive blood pressure readings from MCS and MPMs are not interchangeable; SBP was 6-7 mm Hg higher with the latter. Overestimation beyond MCAD was overwhelming. Caution is required while classifying systolic hypotension with MPMs. Confirmation with auscultatory methods is advisable. More studies are required to evaluate currently available MPMs in different pediatric age groups. How to cite this article: Khan AA, Gupta PK, Baranwal AK, Jayashree M, Sahoo T. Comparison of Blood Pressure Measurements by Currently Available Multiparameter Monitors and Mercury Column Sphygmomanometer in Patients Admitted in Pediatric Intensive Care Unit. Indian J Crit Care Med 2023;27(3):212-221.

Clinical Features Associated With Need for Mechanical Ventilation in Children With Guillain-Barré Syndrome: Retrospective Cohort From India.

OBJECTIVES: To analyze the clinical features associated with the need for mechanical ventilation (MV) in children with Guillain-Barré syndrome (GBS). DESIGN: Retrospective cohort study, 2010-2019. SETTING: PICU. PATIENTS: All children, 1 month to 12 years old, diagnosed with GBS in our single-center PICU. INTERVENTION: Retrospective chart and data review. MEASUREMENTS AND MAIN RESULTS: Out of 189 children identified with a diagnosis of GBS, 130 were boys (69%). The median (interquartile range [IQR]) age was 6 years (3-9 yr). At admission, the Hughes disability score was 5 (4-5), and cranial nerve palsies were present in 81 children (42%). Autonomic instability subsequently occurred in a total of 97 children (51%). In the 159 children with nerve conduction studies, the axonal variant of GBS (102/159; 64%) predominated, followed by the demyelinating variant (38/189; 24%). All children received IV immunoglobulins as first-line therapy at the time of admission. The median (IQR) length of PICU stay was 12 days (3-30.5 d). Ninety-nine children (52%) underwent invasive MV, and median duration of MV was 25 days (19-37 d). At admission, upper limb power less than or equal to 3 (p = 0.037; odds ratio (OR), 3.5 [1.1-11.5]), lower limb power less than or equal to 2 (p = 0.008; OR, 3.5 [1.4-8.9]), and cranial nerve palsy (p = 0.001; OR, 3.2 [1.6-6.1]) were associated with subsequent need for MV. Prolonged (> 21 d) MV was associated with more severe examination findings at admission: upper limb power less than or equal to 2 (p < 0.0001; OR, 4.2 [2.5-6.9]) and lower limb power less than or equal to 1 (p < 0.0001; OR, 4.5 [2.6-7.9]). CONCLUSIONS: In children with GBS, referred to our center in North India, severe neuromuscular weakness at admission was associated with the need for MV. Furthermore, greater severity of this examination was associated with need for prolonged (> 21 d) MV. Identification of these signs may help in prioritizing critical care needs and early PICU transfer.

Congenitally corrected transposition with absent pulmonary valve: Hitherto unreported association.

Absent pulmonary valve has usually been described in association with tetralogy of Fallot. Present case highlights its association with congenitally corrected transposition which has not been reported so far in literature.

Aetiological Profile and Short-Term Neurological Outcome of Haemorrhagic Stroke in Children.

BACKGROUND: Haemorrhagic stroke (HS) accounts for nearly half of the paediatric strokes. The aetiology of HS in childhood is not well defined in the Indian context. OBJECTIVES: To study the aetiological profile and short-term neurological outcome of children with HS from North India. METHODS: In a prospective observational study, consecutive patients >28 days to <12 years of age admitted with a diagnosis of HS were enrolled. Demography, clinical, radiological details and investigations were recorded. Short-term outcomes were assessed at three months follow-up with the Paediatric Cerebral Performance Category scale and Paediatric Stroke Outcome Measure (PSOM). RESULTS: A total of 48 children with HS were enrolled. The median age was 6 months (1-58 months), and 33 (69%) were <2 years old. Vitamin K deficiency-related bleeding disorder (VKDB, 44%), central nervous system infections (19%), arteriovenous malformations (13%) and inherited coagulation disorders (8%) were the most common risk factors for HS. VKDB and inherited coagulation disorders were more frequent in children <2 years of age, and arteriovenous malformations were more frequent in children >2 years of age (p = 0.001). During hospitalization, 21 (44%) children died. Older age, low Glasgow coma score (<8) at admission and paediatric intracerebral haemorrhage score ≥2 were associated with mortality at discharge (p = <0.05). Among survivors, 15 (56%) children had neurological deficits (PSOM >0.5) at three month follow-up. CONCLUSION: VKDB, inherited coagulation disorders, central nervous system infections and arteriovenous malformations were the most common risk factors for HS. VKDB is the single most important preventable risk factor for HS in infants.

Acute Diarrhea and Severe Dehydration in Children: Does Non-anion-gap Component of Severe Metabolic Acidemia Need More Attention?

Background: Despite significant loss of bicarbonate during acute diarrhea, pediatric data are scarce with acute diarrhea/severe dehydration (ADSD) and severe non-anion-gap metabolic acidemia (sNAGMA). We planned to study their clinical profile, critical care needs, and outcome. Patients: Children (1 month-12 years) with ADSD and sNAGMA (pH <7.2 and/or bicarbonate <15 mEq/L, and normal/mixed anion gap) admitted in Pediatric Emergency Department from January 2016 to December 2018 were enrolled. Children with pure high-anion-gap metabolic acidemia were excluded. Methods: Medical records were reviewed retrospectively. The primary outcome was time taken to resolve acidemia. Secondary outcomes were acute care area free days in 5 days (ACAFD5), and adverse outcome as composite of Pediatric Intensive Care Unit (PICU) admission and/or death. Results: Out of 929 diarrhea patients admitted for intravenous therapy, 121 (13%; median age, 4 months) had ADSD and sNAGMA. Median (IQR) pH was 7.11 (7.01-7.22); 21% patients had pH <7.00. Hyperchloremia (96%) and hypernatremia (45%) were common. About 12% patients each required inotropes and ventilation, while 58% had acute kidney injury (AKI). Median (IQR) time for resolution of acidemia among survivors was 24 (12, 24) hours. Thirty-two patients had adverse outcome. Higher grades of sNAGMA were associated with shock, AKI, coma, hypernatremia, hyperkalemia, adverse outcome, and lesser ACAFD5. Shock, ventilation, renal replacement therapy (RRT), and higher grades of sNAGMA were predictors of adverse outcome, with former two being independent predictors. Conclusion: Severe non-anion-gap metabolic acidemia in children with ADSD is associated with organ dysfunctions, dyselectrolytemias, and lesser ACAFD5. Resolution of acidemia took unacceptably longer time. Higher grades of sNAGMA were a predictor of adverse outcomes. Trials are suggested to assess the role of additional bicarbonate therapy. How to cite this article: Takia L, Baranwal AK, Gupta PK, Angurana SK, Jayashree M. Acute Diarrhea and Severe Dehydration in Children: Does Non-anion-gap Component of Severe Metabolic Acidemia Need More Attention? Indian J Crit Care Med 2022;26(12):1300-1307.

Hemophagocytic Lymphohistiocytosis in a PICU of a Developing Economy: Clinical Profile, Intensive Care Needs, Outcome, and Predictors of Mortality.

OBJECTIVES: To describe the clinical profile, intensive care needs, outcome, and predictors of mortality in critically ill children with hemophagocytic lymphohistiocytosis. DESIGN: Retrospective case series. SETTING: PICU of a tertiary care teaching hospital in North India. PATIENTS: Children 2 months to 12 years old with the diagnosis of hemophagocytic lymphohistiocytosis admitted to PICU from January 2012 to April 2019 (7» yr). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sixty-two children with hemophagocytic lymphohistiocytosis (60 secondary and two primary) were enrolled. The median (interquartile range) age of the study group was 82 months (50.5-124 mo). The median (interquartile range) Pediatric Risk of Mortality III score was 16 (10-23). Majority of hemophagocytic lymphohistiocytosis was infection-associated (n = 51; 82.3%). Among these, scrub typhus accounted for 29% of cases (n = 18), dengue 17.7% (n = 11), bacterial sepsis 14.5% (n = 9), enteric fever 6.5% (n = 4), and other infections 14.5% (n = 9). Systemic-onset juvenile idiopathic arthritis accounted for 9.7% of cases (n = 6) and malignancy for 4.8% patients (n = 3). Majority of cases were treated with steroids (77.4%) and IV immunoglobulin (25.8%). Various complications noted were shock (71%), acute kidney injury (66.1%), acute respiratory distress syndrome (41.9%), disseminated intravascular coagulation (54.8%), CNS dysfunction (54.8%), multiple organ dysfunction syndrome (82.3%), and healthcare-associated infections (14.5%). Intensive care needs for primary illness and/or hemophagocytic lymphohistiocytosis included mechanical ventilation (74.2%); packed RBC (72.3%), fresh frozen plasma (40.3%), and platelet (48.4%) transfusion; vasoactive drugs (71%); and renal replacement therapy (24.2%). The median duration of PICU stay was 5 days (2.5-9.5 d) and mortality was 59.7% (n = 37). On univariate analysis, nonsurvivors had higher Pediatric Risk of Mortality III score; higher proportion of shock, acute kidney injury, acute respiratory distress syndrome, disseminated intravascular coagulation, and multiple organ dysfunction syndrome; the need for blood and blood components, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged duration of mechanical ventilation compared with survivors. CONCLUSIONS: Hemophagocytic lymphohistiocytosis in PICU is commonly secondary to tropical infections and associated with high mortality. Higher severity of illness; shock and multiple organ dysfunction syndrome; need for blood and blood products, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged mechanical ventilation predicted death. Treatment of underlying infection and a less intense immunosuppressive therapy (steroids ± IV immunoglobulin) are suggested options. A high index of suspicion for complicating hemophagocytic lymphohistiocytosis is required in children with prolonged fever, cytopenias, organomegaly, and organ dysfunction not responding to conventional treatment.

Cost analysis of pediatric intensive care: a low-middle income country perspective.

BACKGROUND: Globally, Pediatric Intensive Care Unit (PICU) admissions are amongst the most expensive. In low middle-income countries, out of pocket expenditure (OOP) constitutes a major portion of the total expenditure. This makes it important to gain insights into the cost of pediatric intensive care. We undertook this study to calculate the health system cost and out of pocket expenditure incurred per patient during PICU stay. METHODS: Prospective study conducted in a state of the art tertiary level PICU of a teaching and referral hospital. Bottom-up micro costing methods were used to assess the health system cost. Annual data regarding hospital resources used for PICU care was collected from January to December 2018. Data regarding OOP was collected from 299 patients admitted from July 2017 to December 2018. The latter period was divided into four intervals, each of four and a half months duration and data was collected for 1 month in each interval. Per patient and per bed day costs for treatment were estimated both from health system and patient's perspective. RESULTS: The median (inter-quartile range, IQR) length of PICU stay was 5(3-8) days. Mean ± SD Pediatric Risk of Mortality Score (PRISM III) score of the study cohort was 22.23 ± 7.3. Of the total patients, 55.9% (167) were ventilated. Mean cost per patient treated was US$ 2078(₹ 144,566). Of this, health system cost and OOP expenditure per patient were US$ 1731 (₹ 120,425) and 352 (₹ 24,535) respectively. OOP expenditure of a ventilated child was twice that of a non- ventilated child. CONCLUSIONS: The fixed cost of PICU care was 3.8 times more than variable costs. Major portion of cost was borne by the hospital. Severe illness, longer ICU stay and ventilation were associated with increased costs. This study can be used to set the reimbursement package rates under Ayushman Bharat - Pradhan Mantri Jan Arogya Yojana (AB-PMJAY). Tertiary level intensive care in a public sector teaching hospital in India is far less expensive than developed countries.

Thiamine Status in Children with Septic Shock from a Developing Country: A Prospective Case-Control Study.

OBJECTIVE: Mitochondrial dysfunction is central to sepsis-induced multi-organ dysfunction. Thiamine deficiency may contribute to mitochondrial dysfunction and thus high mortality. Study was planned to assess thiamine status in children with septic shock in comparison to healthy controls from a developing country and to study the effect of thiamine levels on its outcome. METHODS: A prospective case-control study (April 2017 to May 2018) enrolling consecutive children with septic shock as 'cases' (n = 76), their healthy siblings (n = 51) and apparently healthy children from immunization clinic (n = 35) as 'controls'. Whole blood total thiamine (WBTT) level was measured on days 1, 10 and 1-month post-discharge. Outcome parameters were acute care area free days on days 14 and 28, and mortality. RESULTS: WBTT [nMol/l; median (interquartile range, IQR)] was significantly lower on day 1 in cases compared with sibling controls [23.1 (21.8-26.3) vs. 36.9 (33.6-40.5); p < 0.001]. It fell further on day 10 [20.8 (18.1-21.1); p < 0.02]. Levels rose significantly 1-month post-discharge [35.5 (31.2-36.6)] and became comparable to sibling controls (p = 0.4). Immunization clinic controls also had lower WBTT [42.3 (40.1-45.9)], but was significantly higher than sibling controls and cases at 1-month post-discharge (p < 0.001). Survivors and non-survivors of septic shock were similar. WBTT levels did not correlate with any of the severity indicators of septic shock or its outcomes. CONCLUSIONS: WBTT was significantly low in all children, and fell further during septic shock. Observed severe deficiency might have precluded any further association of thiamine levels with severity of septic shock and its outcome. Data obtained may inform trials on metabolic resuscitation in paediatric septic shock in developing countries. Lay summaryThiamine deficiency may contribute to high mortality in paediatric septic shock as thiamine is an essential factor for functioning of mitochondria, the powerhouse of the cells. This prospective case-control study was conducted to assess thiamine status in children with septic shock in comparison with healthy controls in a developing country. Consecutive children with fluid-refractory septic shock were enrolled as 'cases'. Their apparently healthy siblings, and apparently healthy children from immunization clinic, were enrolled as 'controls'. The whole blood total thiamine (WBTT) level was measured on days 1, 10 and 1 month after hospital discharge. Seventy-six children were enrolled as cases, 51 children as sibling controls and 35 children as immunization clinic controls. WBTT was significantly lower on day 1 in cases as compared with their sibling controls. It fell further on day 10. The level rose significantly after a month of discharge and became comparable to sibling controls. Immunization clinic controls also had lower WBTT but was significantly higher compared with sibling controls and cases at 1-month post-discharge. Survivors and non-survivors of septic shock had similar WBTT levels. Observed severe deficiency might have precluded any further association of thiamine levels with septic shock outcome.

Epidemiology and Outcomes of Early Morning Neuroparalytic Syndrome Following Snake Bite-A Retrospective Study.

OBJECTIVE: Snake envenomation has been poorly studied in developing countries. 'Early morning neuroparalytic syndrome' (EMNS), the classical clinical constellation caused by krait bites, refers to nighttime, indoor bites where nonspecific symptoms progress to neuroparalysis. Literature regarding EMNS in children is scarce. This study was planned to describe the clinical profile, intensive care needs and predictors of outcome in children with EMNS. METHODS: It is a retrospective study of children below 12 years admitted with a clinical diagnosis of snake envenomation to the pediatric intensive care unit (PICU) of a tertiary care hospital in North India. Patient records were reviewed from the electronic patient database manager. Comparison was made between the EMNS group and the non-EMNS group and between survivors and nonsurvivors within the EMNS group. RESULTS: Of the 111 children with snake envenomation, 76 had neuroparalysis (68%) and 51 had EMNS. In the EMNS cohort, 37 (72.5%) belonged to rural areas, 46 (90.2%) had indoor bites and 39 (76.5%) were witnessed. Patients with EMNS were more likely to have absent fang marks, hypoxemia at admission, bulbar palsy and need for PICU admission. Mortality rate was 13.7% in EMNS; predictors included younger age, presence of ptosis, cardiac arrest at admission and nonavailability of PICU bed (univariable analysis) but none of them independently predicted mortality. CONCLUSION: Younger age, presence of ptosis, cardiac arrest at admission and nonavailability of intensive care beds increase the risk of mortality in children with EMNS. Timely recognition and respiratory support may reduce mortality in these children.

Better Groundwork Can Avoid Troubled Waters: A Developing Country Perspective on Drowning.

OBJECTIVE: Drowning is a leading cause of unintentional injury-related death in low- and middle-income countries (LMICs). This study was undertaken to know the epidemiology, intensive care needs and predictors of outcome of children with drowning. METHODS: Records of children below 12 years admitted with drowning to the emergency room and/or paediatric intensive care unit (PICU) of a tertiary care hospital in North India were retrospectively analysed. 'Favourable outcome' was defined as normal neurological status at discharge (normal cognition and no motor deficits) and 'unfavourable outcome' as death or abnormal neurological status at discharge. Multivariable analysis was done for predictors of unfavourable outcome. RESULTS: Twenty-seven children were analyzed, 14 (51.8%) were boys. Median (IQR) age was 18 months (12-30). The median (IQR) duration of submersion was 4 min (3-9). Six children (22.2%) presented in pulseless arrest, and 7 (43.7%) had both hypoxaemia (saturation <94% on room air) and encephalopathy (GCS <13) at admission. Ten children (37%) were transferred to PICU; principal indications being hypoxic ischaemic encephalopathy (HIE) (n = 6) and ventilation (n = 4). One child died, four survived with sequalae. Predictors of unfavourable outcome on univariable analysis were hypoxaemia, or pulseless arrest at admission, HIE and need for mechanical ventilation; none of these could predict outcome on multivariable analysis. CONCLUSION: Hypoxaemia or pulseless arrest at admission, HIE and need for ventilation predict unfavourable outcome. Appropriate on-site resuscitation and early stabilization may improve outcome in children with drowning in LMIC.

Decompressive craniectomy in pediatric non-traumatic intracranial hypertension: a single center experience.

Purpose: To study the clinical profile and predictors of outcome in children undergoing decompressive craniectomy (DC) for non-traumatic intracranial hypertension (ICH).Materials and methods: Mixed observational study of children, aged 1 month-12 years, who underwent DC for non-traumatic ICH in a tertiary care pediatric intensive care unit from 2012 to 2017. Data on clinical profile and outcome were retrieved retrospectively and survivors were assessed prospectively. The primary outcome was neurological outcome using Glasgow Outcome Scale-Extended (GOS-E) at minimum 6 months' post-discharge. GOS-E of 1-4 were classified as a poor and 5-8 as a good outcome.Results: Thirty children, median (IQR) age of 6.5 (2, 50) months, underwent DC; of which 26 (86.7%) were boys. Altered sensorium (n = 26, 86.7%), seizures (n = 25, 83.3%), pallor (n = 19, 63.3%) and anisocoria (n = 14, 46.7%) were common signs and symptoms. Median (IQR) Glasgow Coma Scale at admission was 9 (6,11). Commonest etiology was intracranial bleed (n = 24; 80%). Median (IQR) time to DC was 24 (24,72) h. Eight (26.7%) children died; 2 during PICU stay and 6 during follow-up. Neurological sequelae at discharge (n = 28) were seizures (n = 25; 89.2%) and hemiparesis (n = 16; 57.1%). Twenty-one children were followed-up at median (IQR) duration of 12 (6,54) months. Good neurological outcome was seen in 14/29 (48.2%) and hemiparesis in 10/21 (47.6%) patients. On regression analysis, anisocoria at admission was an independent predictor of poor outcome [OR 7.33; 95%CI: 1.38-38.87; p = 0.019].Conclusions: DC is beneficial in children with non-traumatic ICH due to a focal pathology and midline shift. Evidence on indications and timing of DC in NTC is still evolving.

Comparison of Ventilator-free Days at 14 and 28 days as a Clinical Trial Outcome in Low- and Middle-income Countries.

AIMS AND OBJECTIVES: Reporting ventilator-free days (VFDs) with time frame of 28 days is a popular composite outcome measure (COM) in trials. However, early deaths and shorter pediatric intensive care unit (PICU) stay predominate in low- and middle-income countries (LMICs). A shorter time frame may reduce sample size required. We planned to compute sample size requirements for different effect sizes from datasets of previously conducted prospective studies for 28-day and 14-day time frames (VFD28 vs VFD14) to examine the hypothesis. MATERIALS AND METHODS: The VFD28 and VFD14 were defined. Datasets of five prospective studies from PICU of our hospital were analyzed to estimate sample sizes for target reductions of 1-9 days in VFDs and other COMs for the two time frames. Reconfirmation of results was done with datasets of two other studies from PICUs of two geographical extremes of the country. RESULTS: Time-to-event occurred within 14 days in majority of patients. Sample size required for VFD14 is about one-fifth to one-sixth of what is required for VFD28 for target reductions of 1-9 days for all the enrolled studies. The same was true for other COMs as well. The hypothesis was supported by datasets of two other studies used for reconfirmation. CONCLUSION: Choice of time frame for assessing VFDs and other COMs in clinical trials should be guided by the clinical context. A shorter time frame may be rewarding in terms of smaller sample size in the prevalent clinical setting of LMICs. Further confirmation with more datasets and prospective studies is desirable. HOW TO CITE THIS ARTICLE: Baranwal AK, Kumar MP, Gupta PK. Comparison of Ventilator-free Days at 14 and 28 days as a Clinical Trial Outcome in Low- and Middle-income Countries. Indian J Crit Care Med 2020;24(10):960-966.

Longitudinal Study of CPK-MB and Echocardiographic Measures of Myocardial Dysfunction in Pediatric Sepsis: Are Patients with Shock Different from Those without?

BACKGROUND: Sepsis-induced myocardial dysfunction has implications on outcome. For lack of echocardiography in resource-limited settings, myocardial biomarkers may be an alternative monitoring tool. OBJECTIVE: This study was planned to explore the longitudinal behavior of creatine phosphokinase-MB (CPK-MB) in children with sepsis with and without shock, and its correlation with clinical and echocardiographic parameters over the first 10 days. DESIGN: Prospective observational study. SETTING: Tertiary care hospital in a lower-middle-income economy of South Asia. PATIENTS: Children (3 months to 12 years) with nonshock sepsis (NSS) (n = 40) and septic shock survivors (SSSs) (n = 40) after optimal resuscitation. Patients with catecholamine refractory shock, preexisting heart disease, and cardiorespiratory event within the past 1 month were excluded from the study. MEASUREMENTS AND MAIN RESULTS: Pediatric logistic organ dysfunction (PeLOD) score, vasoactive inotrope score (VIS), CPK-MB, and echocardiographic measures of myocardial function were recorded on days 1, 3, 7, and 10. Echocardiography was repeated at 1 month. Both groups were similar at baseline. The SSSs had higher CPK-MB (180 vs 53 IU/L; p < 0.001) and PeLOD score (2 ± 0.4 vs 11.7 ± 5.1, p < 0.001) on day 1 compared to the NSS children. More than half of the SSS and none of the NSS patients had myocardial dysfunction. Reduction in CPK-MB over 10 days correlated well with improvement in PeLOD (p < 0.01), VIS (p = 0.04), and echocardiographic measures of myocardial dysfunction (p < 0.05) among SSSs. At 1 month follow-up, all had normal echocardiography. CONCLUSION: The SSSs had markedly elevated CPK-MB, and its fall paralleled the improvement in clinical status and myocardial dysfunctions. The CPK-MB could be a potential monitoring tool for septic cardiomyopathy in resource-limited settings. HOW TO CITE THIS ARTICLE: Baranwal AK, Deepthi G, Rohit MK, Jayashree M, Angurana SK, Kumar-M P. Longitudinal Study of CPK-MB and Echocardiographic Measures of Myocardial Dysfunction in Pediatric Sepsis: Are Patients with Shock Different from Those without? Indian J Crit Care Med 2020;24(2):109-115.

Spontaneous intracranial haemorrhage in children-intensive care needs and predictors of in-hospital mortality: a 10-year single-centre experience.

PURPOSE: Spontaneous intracranial haemorrhage (SICH) in children, although uncommon, is associated with significant mortality and morbidity. Paediatric data is however limited. MATERIAL AND METHODS: Case records of 105 children with SICH, > 1 month to 12 years, admitted to a tertiary level PICU of a teaching and referral hospital between January 2009 and May 2018 were analysed retrospectively. In-hospital mortality was the primary outcome. Variables between survivors and non-survivors were compared to  determine predictors of mortality. RESULTS: The median (IQR) age of subjects was 6 (2.25, 70) months. Common clinical features were altered sensorium (n = 87, 82.9%), seizures (n = 73, 69.5%), pallor (n = 66, 62.9%) and bulging anterior fontanelle (n = 52, 49.5%). Median (IQR) Glasgow Coma Scale (GCS) at admission was 10 (6, 13) with herniation noted in 27 (25.7%) children. Vitamin K deficiency bleeding (VKDB) and arteriovenous malformation (AVM) were the most common etiology for bleeding among infants and older children respectively. The most common site of bleeding was intracerebral (n = 47, 44.8%) followed by subdural (n = 26; 24.8%). Sixteen (15.2%) children died during hospital stay. On univariate analysis, GCS < 8, Pediatric Risk of Mortality score (PRISM III) > 20, need for intubation, thiopentone coma for refractory intracranial pressure (ICP) and progression to shock and acute kidney injury (AKI) predicted mortality. Seizures were favourably associated with survival. Age, site of bleeding, etiology or type of management for raised ICP (conservative versus decompressive craniectomy) did not affect the outcome. On multivariable analysis, progression to AKI (OR 5.86; 95% CI, 1.53-22.4; p 0.01) predicted poor outcome. Seizures, however, were associated with better odds for survival (OR 0.12; 95% CI, 0.03-0.47; p 0.002). CONCLUSIONS: VKDB and AVM were the common etiologies among infants and older children respectively. Age, site, etiology of bleeding and type of management did not affect outcome. Severe decompensation at presentation, thiopentone for refractory ICP and progression to multiorgan dysfunction determined mortality.

Suspecting Hyperferritinemic Sepsis in Iron-Deficient Population: Do We Need a Lower Plasma Ferritin Threshold?

OBJECTIVES: Hyperferritinemia is being suggested to identify patients with sepsis-induced macrophage activation syndrome for early intervention. However, data among iron-deficient children are scarce. This study was planned to explore the biological behavior of plasma ferritin in children from communities with a high frequency of iron deficiency with septic shock and its association with the outcome. DESIGN: Prospective observational study. SETTING: Tertiary care teaching hospital in a low-middle income economy of South Asia. PATIENTS OR SUBJECTS: Patients (6 mo to 12 yr) (n = 42) with septic shock and their healthy siblings as controls (n = 36). Patients/controls with blood transfusion/iron supplement during last 6 months or with any chronic disease were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ferritin was measured in patients at enrollment and then at 1 month of hospital discharge while they were not on iron supplementation and in controls as indicative of baseline level. Patients' median age was 30 months (13.5-87 mo), 31% were malnourished, majority (86%) had anemia, and two thirds had microcytic hypochromic red cells. Ferritin at admission was 763 ng/mL (480-1,820 ng/mL) in nonsurvivors, whereas 415 ng/mL (262-852 ng/mL) in survivors (p = 0.11). Pediatric Logistic Organ Dysfunction score and C-reactive protein correlated positively with plasma ferritin (p = 0.03 and p = 0.01, respectively) at enrollment. Elevated ferritin of greater than 500 ng/mL (relative risk, 2.48; 95% CI, 0.95-6.43) and greater than 1,000 ng/mL (relative risk, 1.94; 95% CI, 0.94-4.02) were associated with higher mortality but not independently. Among survivors, the 1-month follow-up ferritin fell significantly to 97 ng/mL (16-118 ng/mL) (p = 0.001). However, it was still significantly higher than that in sibling controls (19 ng/mL [10-54 ng/mL]) (p = 0.003). CONCLUSIONS: Ferritin rises significantly in septic shock patients despite iron deficiency and seems to correlate with the severity of inflammation and organ dysfunction. Even a lower threshold (of 500 or 1,000 ng/mL) could predict higher mortality. It may suggest the need for redefining the plasma ferritin threshold for suspecting hyperferritinemic sepsis and sepsis-induced macrophage activation syndrome in these patients. Larger studies with frequent ferritin measurements are desirable to validate these initial observations.

Subdural empyema due to Salmonella paratyphi B in an infant: a case report and review of literature.

Intracranial infection due to Salmonella is uncommon in children. Subdural empyema (SDE) is described with Salmonella typhi as a complication of meningitis. We report a 6-month-old infant with SDE secondary to Salmonella paratyphi B who had presented with prolonged fever and enlarging head. A literature review of Salmonella SDE in infants with respect to clinical course and outcome is presented.

High-dose Oral Ambroxol for Early Treatment of Pulmonary Acute Respiratory Distress Syndrome: an Exploratory, Randomized, Controlled Pilot Trial.

OBJECTIVE: To evaluate efficacy of high-dose oral ambroxol in acute respiratory distress syndrome (ARDS) with respect to ventilator-free days (VFD). DESIGN: Prospective, randomized, placebo-controlled, blinded pilot trial. PATIENTS: Sixty-six mechanically ventilated patients (1 month to 12 years) with ARDS who were hand-ventilated for <24 hr before pediatric intensive care unit admission. INTERVENTIONS: Patients randomized to oral ambroxol (40 mg/kg/day, in four divided doses) (n = 32) or placebo (n = 34) until 10 days, extubation or death whichever is earlier. MEASUREMENTS AND MAIN RESULTS: Majority (91%) had pneumonia and bronchiolitis. Two study groups were similar in baseline characteristics. Mean partial pressure of arterial oxygen/fraction of inspired oxygen and oxygenation index were >175 and <10, respectively, with no difference in the two study groups. VFD were similar in the two study groups. Overall mortality was 26%. No adverse events were noted with ambroxol. CONCLUSIONS: Among ventilated pulmonary ARDS patients with oxygenation index of <10, mortality was 26%. Ambroxol did not improve VFD. Study with higher and more frequently administered doses of ambroxol in larger sample is suggested after having generated relevant pharmacokinetic data among critically ill children.