Early recognition and management of septic shock in children

Septic shock remains a major cause of morbidity and mortality among children, mainly due to acute hemodynamic compromise and multiple organ failures. In the last decade, international guidelines for the management of septic shock, as well as clinical practice parameters for hemodynamic support of pediatric patients, have been published. Early recognition and aggressive therapy of septic shock, by means of abundant fluid resuscitation, use of catecholamines and other adjuvant drugs, are widely considered of pivotal importance to improve the short and long-term outcome of these patients. The aim of this paper is to summarize the modern approach to septic shock in children, particularly in its very initial phase, when pediatric healthcare providers may be required to intervene in the pre-intensive care unit setting or just on admission in the pediatric intensive care unit

Weaning newborn infants from mechanical ventilation

Invasive mechanical ventilation is a life-saving procedure which is largely used in neonatal intensive care units, particularly in very premature newborn infants. However, this essential treatment may increase mortality and cause substantial morbidity, including lung or airway injuries, unplanned extubations, adverse hemodynamic effects, analgosedative dependency and severe infectious complications, such as ventilator-associated pneumonia. Therefore, limiting the duration of airway intubation and mechanical ventilator support is crucial for the neonatologist, who should aim to a shorter process of discontinuing mechanical ventilation as well as an earlier appreciation of readiness for spontaneous breathing trials. Unfortunately, there is scarce information about the best ways to perform an effective weaning process in infants undergoing mechanical ventilation, thus in most cases the weaning course is still based upon the individual judgment of the attending clinician. Nonetheless, some evidence indicate that volume targeted ventilation modes are more effective in reducing the duration of mechanical ventilation than traditional pressure limited ventilation modes, particularly in very preterm babies. Weaning and extubation directly from high frequency ventilation could be another option, even though its effectiveness, when compared to switching and subsequent weaning and extubating from conventional ventilation, is yet to be adequately investigated. Some data suggest the use of weaning protocols could reduce the weaning time and duration of mechanical ventilation, but better designed prospective studies are still needed to confirm these preliminary observations. Finally, the implementation of short spontaneous breathing tests in preterm infants has been shown to be beneficial in some centres, favoring an earlier extubation at higher ventilatory settings compared with historical controls, without worsening the extubation failure rate. Further research is still required to identify the best practices capable to shorten the duration of mechanical ventilation in term and preterm infants, at the same time keeping to a minimum the risk of extubation failure.   Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy) · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge researc

Is there any role for terlipressin in the extremely low birth weight infant with refractory septic shock?

Terlipressin, a synthetic long-acting analogue of vasopressin, has been investigated as a second line vasopressor in adults and children with refractory septic shock, i.e. not responding to fluid resuscitation and high-dose catecholamine administration. Little experience is available about the safety and efficacy of terlipressin in term and preterm newborns. We report the case of an extremely low birth weight infant with severe septic shock, unresponsive to fluids, noradrenalin and hydrocortisone, in whom terlipressin was attempted as a rescue drug. Despite three doses of terlipressin, administered 6-hourly, the patient remained profoundly hypotensive and eventually died. Further studies are required before any recommendation on the use of terlipressin in term or preterm newborns with septic shock can be made

Cell Population Data (CPD) for Early Recognition of Sepsis and Septic Shock in Children: A Pilot Study

Objectives: Innovative Cell Population Data (CPD) have been used as early biomarkers for diagnosing sepsis in adults. We assessed the usefulness of CPD in pediatric patients with sepsis/septic shock, in terms of early recognition and outcome prediction. We revised 54 patients (0-15 y) admitted to our Pediatric Intensive Care Unit (PICU) for sepsis/septic shock during a 4-year period. Twenty-eight patients were excluded, 26 septic patients were enrolled (G1). Forty children admitted for elective surgery served as controls (G2). Data on five selected CPD parameters, namely neutrophils fluorescence intensity (NE-SFL), monocytes cells complexity (MO-X), monocytes fluorescence intensity (MO-Y), monocytes complexity and width of dispersion of events measured (MO-WX), and monocytes cells size and width dispersion (MO-WZ), were obtained at time of PICU admission (t0) by a hematological analyzer (Sysmex XN 9000\uae). As the primary outcome we evaluated the relevance of CPD for diagnosing sepsis/septic shock on PICU admission. Furthermore, we investigated if CPD at t0 were correlated with C-reactive protein (CRP), patient survival, or complicated sepsis course. Results: On PICU admission (t0), NE-SFL, MO-WX, and MO-Y were higher in sepsis/septic shock patients compared to controls. NE-SFL values were correlated with CRP values in G1 patients (r = 0.83). None of the five CPD parameters was correlated with survival or complicated sepsis course. Conclusion: We found higher values of NE-SFL, MO-WX, and MO-Y in children with sepsis/septic shock upon PICU admission. These parameters may be a promising adjunct for early sepsis diagnosis in pediatric populations. Larger, prospective studies are needed to confirm our preliminary observations

Congenital Heart Disease: Growth Evaluation and Sport Activity in a Paediatric Population

(1) Objective: To evaluate: (i) the associations of age and disease severity with anthropometric indices and weight status, (ii) the difference in the frequency of sports activity among different levels of disease severity in paediatric patients with congenital heart disease (CHD). (2) Methods: Clinical data of Caucasian children (aged 2-18 years) diagnosed with CHD (2005-2018) were retrospectively collected from the electronic register of outpatient visits. Of the 475 children with CHD, 368 children and their 1690 complete anthropometric measurements were eligible for inclusion in our analysis. (3) Results: Significant increase with age was observed for weight z-score [beta (95%CI): 0.03 (0.02, 0.05) for one-unit of age] and BMI z-score [0.06 (0.03, 0.08)] but not for height z-score. The probability of being underweight and overweight/obese increased and decreased with disease severity, respectively. The obesity probability of patients with mild CHD (0.06 [95%CI: 0.03, 0.08]) was not statistically distinguishable from that of patients with moderate CHD (0.03 [95%CI: 0.02, 0.05]), whereas it was lower in patients with severe CHD (0.004 [95%CI: 0.0, 0.009]). No obese patients with a univentricular heart defect were observed. Days spent in sport activities were equal to 1.9 [95%CI: 1.6, 2.2] days/week, 1.9 [1.5, 2.2], 1.4 [1.1, 1.7] and 0.7 [0.1, 1.3] in patients with mild, moderate, severe and univentricular CHD, respectively. (4) Conclusions: The risk of being overweight and obese should not be underestimated in paediatric patients diagnosed with CHD, especially in children with mild or moderate heart defects. It could be prevented or reduced by promoting a healthy lifestyle

Systemic Catheter-Related Venous Thromboembolism in Children: Data From the Italian Registry of Pediatric Thrombosis.

BACKGROUND: Central venous catheters (CVCs) represent one of the main risk factors for venous thrombotic events (VTEs) in children. METHODS: We studied the Italian Registry of Pediatric Thrombosis (RITI) with regard to systemic radiologically confirmed CVC-related VTEs (CVC-VTEs) occurred during 6.5 years in children aged 29 days to 18 years. RESULTS: A total of 78 CVC-VTEs were included, which occurred in 76 patients (40/76, 53% males). CVC-VTEs comprised 67 non-cardiac VTEs (86%) and 11 intracardiac thrombotic events (ICTEs) (14%); the median age at onset was 19 and 17 months, respectively. The most frequent reason for CVC insertion was supportive therapy. The catheters were placed percutaneously in 85% of cases (56/66) and surgically in the remaining 15% (10/66). Peripherally inserted central catheters (PICCs) were used in 47% (31/66) cases, partially implanted catheters in 42% (28/66), non-implantable catheters in 7% (5/66), and totally implanted catheters (Port) in 2% (1/66). CVC-VTEs were symptomatic in 77% of cases (60/78), while in the remaining 23%, they were incidentally detected on the imaging performed for the underlying condition. The median time between CVC insertion and the onset of symptoms was 10 days in non-cardiac VTEs and 39 days in ICTEs. Doppler ultrasound was the diagnostic technique most frequently used. The venous compartment most frequently affected was the veins of the lower extremities (52%, 43/73). Anti-thrombotic treatment was administered in 96% of CVC-VTEs (75/78). About 2.6% (2/76) of patients experienced a second thrombotic event. At discharge, post-thrombotic syndrome was reported in 13.5% (5/37) events with available data, CVC replacement in 10.8% (4/47), and ischemic necrosis with toe finger amputation in 2.7% (1/37). Three patients died due to an underlying condition; no CVC-VTE-related deaths were reported. CONCLUSIONS: We have carried out a registry-based study on CVC-VTEs in the children in Italy, providing the data that may help improve the detection and management of this CVC-related complication

Paediatric arterial ischaemic stroke and cerebral sinovenous thrombosis: First report from the Italian registry of pediatric thrombosis (R. I. T. I., Registro Italiano Trombosi Infantili)

reserved55noData from large case series of children with cerebral thrombotic events are pivotal to improve prevention, early recognition and treatment of these conditions. The Italian Registry of Pediatric Thrombosis (R. I. T. I.) was established in 2007 by a multidisciplinary team, aiming for a better understanding of neonatal and paediatric thrombotic events in Italy and providing a preliminary source of data for the future development of specific clinical trials and diagnostic-therapeutic protocols. We analysed data relative to the paediatric cerebral thrombotic events of the R. I. T. I. which occurred between January 2007 and June 2012. In the study period, 79 arterial ischaemic stroke (AIS) events (49 in males) and 91 cerebral sinovenous thrombosis (CSVT) events (65 in males) were enrolled in the R. I. T. I. Mean age at onset was 4.5 years in AIS, and 7.1 years in CSVT. Most common modes of presentation were hemiparesis, seizures and speech disturbances in AIS, and headache, seizures and lethargy in CSVT. Most common etiologies were underlying chronic diseases, vasculopathy and cardiopathy in AIS, and underlying chronic diseases and infection in CSVT. Time to diagnosis exceeded 24 hours in 46% AIS and 59% CSVT. Overall data from the Italian Registry are in substantial agreement with those from the literature, despite small differences. Among these, a longer time to diagnosis compared to other registries and case series poses the accent to the need of an earlier recognition of paediatric cerebrovascular events in Italy, in order to enable prompt and effective treatment strategies.mixedSuppiej A.; Gentilomo C.; Saracco P.; Sartori S.; Agostini M.; Bagna R.; Bassi B.; Giordano P.; Grassi M.; Guzzetta A.; Lasagni D.; Luciani M.; Molinari A.C.; Palmieri A.; Putti M.C.; Ramenghi L.A.; Rota L.L.; Sperli D.; Laverda A.M.; Simioni P.; Angriman M.; Aru A.B.; Barisone E.; Bartalena L.; Berta M.; Bertoni E.; Cancarini P.; Cavaliere E.; Celle M.E.; Cerbone A.M.; Cesaroni E.; Via L.D.; Dell'Oro M.G.; Di Rosa G.; Ferrari G.M.; Fiori S.; Gaffuri M.; Gallina M.R.; Gimmillaro A.; Grandone E.; Ladogana S.; Laforgia N.; La Piana R.; Maschio F.; Miniero R.; Nosadini M.; Panzeri D.; Petrucci A.; Piersigilli F.; Sala D.; Sangermani R.; Santoro N.; Tufano A.; Ventura G.; Vittorini R.Suppiej, A.; Gentilomo, C.; Saracco, P.; Sartori, S.; Agostini, M.; Bagna, R.; Bassi, B.; Giordano, P.; Grassi, M.; Guzzetta, A.; Lasagni, D.; Luciani, M.; Molinari, A. C.; Palmieri, A.; Putti, M. C.; Ramenghi, L. A.; Rota, L. L.; Sperli, D.; Laverda, A. M.; Simioni, P.; Angriman, M.; Aru, A. B.; Barisone, E.; Bartalena, L.; Berta, M.; Bertoni, E.; Cancarini, P.; Cavaliere, E.; Celle, M. E.; Cerbone, A. M.; Cesaroni, E.; Via, L. D.; Dell'Oro, M. G.; Di Rosa, G.; Ferrari, G. M.; Fiori, S.; Gaffuri, M.; Gallina, M. R.; Gimmillaro, A.; Grandone, E.; Ladogana, S.; Laforgia, N.; La Piana, R.; Maschio, F.; Miniero, R.; Nosadini, M.; Panzeri, D.; Petrucci, A.; Piersigilli, F.; Sala, D.; Sangermani, R.; Santoro, N.; Tufano, A.; Ventura, G.; Vittorini, R

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research