Objective:To study the early predictors of refractory septic shock (RSS) in neonates.Methods:From July 2020 to December 2021, clinical data of neonates with septic shock admitted to the Neonatal Department of our hospital were retrospectively reviewed. According to the maximum septic shock score (SSS) during clinical course, the neonates were assigned into RSS group and non-RSS group. Perinatal data, laboratory results and hemodynamic parameters at diagnosis were compared between the two groups. Multiple logistic regression analysis was used to identify independent risk factors of RSS and septic shock-related death. Receiver operating characteristic (ROC) curve was constructed to evaluate the early predictors of poor prognosis.Results:A total of 130 neonates were enrolled, including 54 in RSS group and 76 in non-RSS group. Compared with the non-RSS group, the RSS group had significantly lower pH, base excess (BE), stroke volume index (SVI), cardiac output (CO) and cardiac index (CI).Meanwhile, the RSS group had significantly higher mean arterial pressure (MAP) to CI ratio (MAP/CI) and SSS [including bedside SSS (bSSS), computed SSS (cSSS) and modified version of cSSS (mcSSS)] (all P<0.05). Multiple logistic regression analysis showed that increased MAP/CI was an independent predictor of RSS. The cut-off value of MAP/CI was 11.6 [sensitivity 62%, specificity 87%, positive predictive value (PPV) 79% and negative predictive value (NPV) 77%], with an area under the curve (AUC) of 0.734. Increased mcSSS was an independent predictor of septic shock-related death. The cut-off value of mcSSS was 5.8 (sensitivity 83%, specificity 72%, PPV 21% and NPV 97%), with an AUC of 0.845. Conclusions:Increased MAP/CI (≥11.6) and mcSSS (≥5.8) may be early predictors of RSS and septic shock-related death in neonates.

Persistent pulmonary hypertension of the newborn (PPHN) is a common and critical disease in the neonatus characterized by persistent pulmonary hypertension and hypoxemia, with a high mortality.Except for intubation and ventilator support, recognized treatments often require the application of pulmonary vasodilators drugs, such as inhaled nitric oxide, Sildenafil, etc, each with its own advantages.In recent years, L-citrulline, as a potential therapeutic option, has shown huge potential in PPHN treatment.The purpose of this review is to explore the possible potential of L-citrulline in the treatment of PPHN in terms of therapeutic mechanism, pharmacokinetics, current status of research and future perspectives.

Objective:To investigate the influence of combining therapy of massage on sacro-2 to sacro-4 spinal cord reflexion area and anal dilatation therapy on constipation after cerebral apoplexy and promote the rehabilitation of defecation function in patients with constipation after stroke.Methods:Aandomized controlled study method was chosen, 80 patients with constipation after cerebral apoplexy treated in Guangzhou Traditional Chinese Medicine Hospital from August 2018 to July 2019 were selected as research subjects by convenience sampling. The enrolled patients were divided into 2 groups, 40 to the observation group and 40 to the control group by random number table method. On the basis of routine constipation related nursing measures, the control group was given anal dilatation therapy, while the observation group′s treatment was given massage on sacro-2 to sacro-4 spinal cord reflexion area combined with anal dilatation therapy. Before intervention and after intervention, the changes of therapeutic effect of constipation effect, constipation symptoms scores and the degree of neurological deficit were all compared between the two groups.Results:There were 22 males and 18 females in the observation group; age ranged from 40 to 75 (63.33 ± 8.49) years old; in the control group, there were 23 males and 17 females, aged 41-74 (63.03 ± 7.60) years old. Before intervention, there was no statistically significant difference in constipation symptom scores and neurological deficits between the two groups (both P>0.05). After intervention, the score of constipation symptoms was (3.80 ± 2.05) points and the score of the degree of neurological deficit was (7.58 ± 2.69) points in the observation group, both lower than (5.18 ± 3.52) points and (8.90 ± 2.73) points in the control group with statistically significant differences between the two groups ( t values were respectively -2.13 and -2.19, both P<0.05). The total efficacy of the observation group was 97.50% (39/40), which was significantly higher than 87.50% (35/40) of the control group with statistically significant differences between the two groups ( χ2 = - 2.11, P<0.05). Conclusions:Nursing intervention of massage on sacro-2 to sacro-4 spinal cord reflexion area combined with anus dilatation therapy on constipation after cerebral apoplexy can effectively reduce the symptoms of constipation and lowered the degree of neurological deficit, which is beneficial to the functional rehabilitation of patients with cerebral apoplexy.

Objective:To study the predictive value of vasoactive-inotropic score (VIS), fluid overload (FO) and lactate level for the outcome of preterm infants with refractory septic shock.Methods:Preterm infants diagnosed with refractory septic shock and required hydrocortisone treatment in our Department from January 2016 to December 2021 were analyzed retrospectively. Preterm infants were assigned into three gestational age groups (<28 weeks, 28-31 weeks, 32-36 weeks). According to the outcome of the disease, the children were further divided into good prognosis group and poor prognosis group. The relationship between the maximum VIS, FO and the mean lactic acid before hydrocortisone and the outcome of refractory septic shock was analyzed by receiver operating characteristic (ROC) curve, the cut-off point of ROC curve was calculated to obtain the predictive efficacy of the three indicators for the outcome of refractory septic shock in preterm infants.Results:A total of 50 preterm infants with refractory septic shock and received hydrocortisone treatment were enrolled, including 20 in the good prognosis group and 30 in the poor prognosis group. There were no significant differences in the maximum VIS, FO and mean lactic acid before hydrocortisone treatment between the two groups of gestational age of <32 weeks ( P> 0.05). The maximum VIS, FO and mean lactic acid of gestational age of 32-36 weeks in the poor prognosis group were higher than those in the good prognosis group, VIS: 56.1±15.7 vs. 37.1±12.9, FO (%): 108.2 (78.6,137.7) vs. 55.5 (10.3, 100.7), and mean lactic acid (mmol/L): 8.3 (4.6, 12.0) vs. 4.8 (-0.8, 10.5), all P<0.05. The area under the ROC curve of the mean lactic acid was the largest, the cut-off value was 4.1 mmol/L, and the Youden index was 1.732. Conclusions:VIS, FO and lactate level are difficult to be used for determining the outcome of refractory septic shock in preterm infants of <32 weeks. While the mean lactic acid has the best predictive performance in preterm infants of 32-36 weeks.

Objective:To explore the effect of quality improvement of hemodynamic monitoring on fluid overload (FO) and outcome in newborns with septic shock.Methods:Non-invasive cardiac output monitoring and functional cardiac ultrasound quality improvement program was started during January 2020 in our hospital. Neonates with septic shock admitted before and after the program were retrospectively analyzed. From January 2018 to December 2019 was pre-improvement period when fluid resuscitation was routinely performed and vasoactive drugs was selected empirically. From January 2020 to December 2021 was post-improvement period when fluid resuscitation and/or use and adjustment of vasoactive drugs were guided by hemodynamic parameters. The 24 h, 48 h, 72 h FO, duration of invasive respiratory support, vasoactive-inotropic score, septic shock score, incidences of complications and all-cause mortality were compared between the two groups.Results:A total of 284 eligible cases were enrolled, including 136 cases in pre-improvement group and 148 cases in post-improvement group. Post-improvement group had significantly lower gestational age (GA), birth weight (BW) and body weight at disease onset than pre-improvement group ( P<0.05). Incidences of 48 h and 72 h FO, fluid resuscitation volume within 72 h, pulmonary hemorrhage and periventricular leukomalacia (PVL) were significantly lower in the post-improvement group ( P<0.05). No significant differences existed in 24 h FO, other complications and all-cause mortality between the two groups ( P>0.05). No significant differences existed in GA and BW for neonates with pulmonary hemorrhage and PVL between the two groups ( P>0.05). Conclusions:Quality improvement of hemodynamic monitoring can effectively improve FO and reduce the incidences of pulmonary hemorrhage and PVL.

Objective:To study the efficacy of norepinephrine in the treatment of neonates with septic shock.Methods:A prospective observation study of neonates with septic shock, who received norepinephrine in the neonatal intensive care unit of Guangdong Women and Children's Hospital from January 2019 to November 2020. All infants had functional echocardiography for hemodynamic monitoring before norepinephrine treatment and 1 hour thereafter blood pressure, heart rate, arterial blood gas analyses were recorded at the same time. The intravenous fluid volume and urine volume from the diagnosis of shock to the commencement of norepinephrine therapy (T0) and 24 hours thereafter (T1) were recorded, and the hemodynamic parameters, vasoactive drugs and clinical outcomes were analyzed.Results:A total of 66 newborns were enrolled, including 27 cases of mild shock, 33 cases of moderate shock and 6 cases of severe shock. 48 were male infants, 38 cases were premature infants. The gestational age was (35.2±4.1) weeks and the birth weight was (2 476±909) g. The median time of shock diagnosis was 2 days after birth, and the median shock score was 4 points. The median time from the diagnosis of shock to the start of norepinephrine treatment was 7.5 hours. Compared with that before norepinephrine treatment, stroke volume, stroke volume index, cardiac output, cardiac index, left ventricular ejection fraction, shortening fraction, systolic blood pressure, diastolic blood pressure, mean arterial pressure, blood pH and BE at 1 hour after treatment were increased, heart rate and blood lactic acid were decreased, the differences were statistically significant ( P<0.05). Urine volume was increased 24 hours after treatment ( P<0.05), and fluid overload decreased ( P<0.05). The maximum dopamine dose, the down-regulation time and duration of vasoactive drugs were positively correlated with the time to start norepinephrine therapy ( r=0.325、 r=0.383、 r=0.319, P<0.05). Among the 66 infants, 58 infants with shock had been corrected and 14 infants died within 28 days. Conclusions:Norepinephrine is effective and feasible in the treatment of neonatal septic shock and can significantly improve hemodynamic parameters.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To study the predictive value of vasoactive-inotropic score (VIS), shock score and lactate level for the outcome of term infants with septic shock.Methods:From January 2019 to October 2020, clinical data of term infants with septic shock admitted to our department were reviewed. According to their clinical outcome, the infants were assigned into the survival group and the deceased group and the differences of the two groups were compared. Logistic regression was used to determine the risk factors of mortality in term infants with septic shock. Receiver operating characteristic curve was used to compare the predictive efficacy of VIS, shock score and lactate level for the outcome of septic shock.Results:Significant differences existed between the survival group and the deceased group in the following: maximum VIS, maximum shock score, maximum lactate level, the mean value of VIS during the second 24 h, the mean value of lactate during the first and second 24 h ( P < 0.05). Meanwhile, maximum VIS ( OR = 1.038, 95% CI 1.014~1.063), maximum shock score ( OR = 2.372, 95% CI 1.126~4.999) and the mean value of lactate during the first 24h ( OR = 2.983, 95% CI 1.132~7.862) were correlated with mortality in the infants ( P < 0.05). The area under the curve of maximum VIS was the most prominent, with 58.5 as cut-off. Conclusions:Among the three indicators, VIS has the best predictive value for mortality outcome in term infants with septic shock, followed by shock score and lactate level.

Objective:To study the threshold of fluid overload (FO) and its risk factors in neonatal septic shock.Methods:From January 2019 to November 2020, clinical data of infants with septic shock hospitalized in the neonatal department of our hospital were reviewed. With poor prognosis as the outcome, ROC curve was drawn based on 24 h (from the beginning of septic shock), 48 h and 72 h FO value. FO cutoff value was determined as area under curve (AUC) reached maximum. Risk factors of FO were analyzed between FO

Objective:To study the clinical value of neonatal shock score (NSS) and septic shock score (SSS) in the evaluation of mortality and serious complications of neonatal refractory septic shock.Method:From January 2019 to November 2020, clinical data of neonates with septic shock admitted to Neonatal Department of our hospital were retrospectively reviewed. According to the final outcomes, neonates were assigned into good prognosis group (neonates survived without serious complications) and poor prognosis group (neonates were dead within 28 days after birth and/or had serious complications). The NSS and SSS were calculated according to the worst value of each index during the septic shock course. SSS included computed septic shock score (cSSS) and bedside septic shock score (bSSS). The receiver operating characteristic (ROC) curve was used to analyze the efficacy of each scoring system evaluating the risk of poor prognosis due to septic shock. The correlation of each scoring system with the duration of vasoactive drugs was analyzed using Spearman rank correlation analysis.Result:A total of 72 neonates were enrolled, including 45 in good prognosis group and 27 in poor prognosis group. The vasoactive drug score, serum lactate level, NSS and cSSS in poor prognosis group were significantly higher than good prognosis group ( P<0.05).And bSSS score showed no significant differences between the two groups ( P>0.05). The area under the ROC curve (AUC) of NSS and cSSS predicting the adverse prognosis of neonates with septic shock were 0.644 (95% CI 0.510~0.777, P<0.05) and 0.765 (95% CI 0.654~0.877, P<0.05). The best cut-off values for NSS and cSSS predicting poor prognosis were 4.0 and 80.5, respectively. The positive predictive value (PPV) (81.3% vs. 47.5%) and negative predictive value (NPV) (75.0% vs. 70.6%) of cSSS were higher than NSS. Spearman rank correlation analysis showed that cSSS was positively correlated with the duration of vasoactive drugs( r=0.487, P<0.01). Conclusion:Both shock scoring systems have an evaluation value for the prognosis of neonatal septic shock. The evaluation value of cSSS is better than NSS, and can be used as a main tool for the evaluation of neonatal refractory septic shock.