Analgesia and sedation in preterm neonates who require ventilatory support: results from the NOPAIN trial. Neonatal Outcome and Prolonged Analgesia in Neonates

BACKGROUND: Preterm neonates are exposed to multiple painful procedures after birth and exhibit acute physiological responses to pain. Occurrence of early intraventricular hemorrhage within 24 to 72 hours after birth suggests a role of pain and stress in the multifactorial causation of severe intraventricular hemorrhage and periventricular leukomalacia. We proposed that such neurologic outcomes in preterm neonates who require ventilatory support may be reduced by morphine analgesia or midazolam sedation compared with a placebo. OBJECTIVES: To define the incidence of clinical outcomes in the target study population, to estimate the effect size and adverse effects associated with analgesia and sedation, and to calculate the sample size for a definitive test of this hypothesis. METHODS: Sixty-seven preterm neonates were randomized in a pilot clinical trial from 9 centers. Neonates of 24 to 32 weeks gestation were eligible if they had been intubated and required ventilatory support for less than 8 hours and if they were enrolled within 72 hours after birth. Exclusion criteria included major congenital anomalies, severe intrapartum asphyxia, and participation in other research studies. Severity of illness was assessed by the Clinical Risk Index for Babies, and neonates were randomized to receive continuous infusions of morphine sulfate, midazolam hydrochloride, or 10% dextrose (placebo). Masked study medications were continued as long as clinically necessary, then weaned and stopped according to predefined criteria. Levels of sedation (COMFORT scores) and responses to pain (Premature Infant Pain Profile scores) were measured before, during, and 12 hours after discontinuation of drug infusion. Cranial ultrasound examinations were performed as part of routine practice, and poor neurologic outcomes were defined as neonatal death, severe intraventricular hemorrhage (grade III or IV), or periventricular leukomalacia. RESULTS: No significant differences occurred in the demographic, clinical, and socioeconomic variables related to mothers and neonates in the 3 groups or in the severity of illness at birth as measured by Clinical Risk Index for Babies scores. Two neonates in the placebo group and 1 neonate in the midazolam group died; no deaths occurred in the morphine group. Poor neurologic outcomes occurred in 24% of neonates in the placebo group, 32% in the midazolam group, and 4% in the morphine group (likelihood ratio chi2 = 7.04, P = .03). Secondary clinical outcomes and neurobehavioral outcomes at 36 weeks' postconceptional age were similar in the 3 groups. Responses elicited by endotracheal tube suction (Premature Infant Pain Profile scores) were significantly reduced during the morphine (P<.001) and midazolam (P = .002) infusions compared with the placebo group. CONCLUSIONS: This pilot trial suggests that preemptive analgesia given by continuous low-dose morphine infusion may reduce the incidence of poor neurologic outcomes in preterm neonates who require ventilatory support. Limitations in the sample size of this pilot study suggest that these results should be confirmed in a large multicenter randomized trial.     

Randomised controlled trial evaluating effects of morphine on plasma adrenaline/noradrenaline concentrations in newborns

OBJECTIVES: To determine the effects of continuous morphine infusion in ventilated newborns on plasma concentrations of adrenaline (epinephrine) and noradrenaline (norepinephrine) and their relation to clinical outcome. DESIGN: Blinded, randomised, placebo controlled trial. SETTING: Level III neonatal intensive care units in two centres. PATIENTS: A total of 126 ventilated neonates (inclusion criteria: postnatal age <3 days, duration of ventilation <8 hours, indwelling arterial catheter for clinical purposes; exclusion criteria: severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers). INTERVENTIONS: Plasma adrenaline and noradrenaline concentrations were determined in patients during blinded morphine (n = 60) and placebo (n = 66) infusion (100 microg/kg plus 10 microg/kg/h). RESULTS: Plasma concentrations at baseline (nmol/l with interquartile range in parentheses) were comparable in infants treated with morphine (adrenaline, 0.22 (0.31); noradrenaline, 2.52 (2.99)) or placebo (adrenaline, 0.29 (0.46); noradrenaline, 2.44 (3.14)). During infusion, median adrenaline concentrations were 0.12 (0.28) and 0.18 (0.35) and median noradrenaline concentrations were 2.8 (3.7) and 3.8 (4.0) for the morphine and placebo treated infants respectively. Multivariate analyses showed that noradrenaline (p = 0.029), but not adrenaline (p = 0.18), concentrations were significantly lower in the morphine group than the placebo group. Furthermore, noradrenaline concentrations were related to the length of stay in the neonatal intensive care unit. CONCLUSIONS: Continuous morphine infusion significantly decreased plasma noradrenaline concentrations in ventilated newborns compared with placebo treatment. The results of this study support the idea that routine morphine administration decreases stress responses in ventilated neonates.     

Morphine in ventilated neonates: its effects on arterial blood pressure

OBJECTIVE: To study the effects of continuous morphine infusion on arterial blood pressure in ventilated neonates. DESIGN: Blinded randomised placebo controlled trial. SETTING: Level III neonatal intensive care unit in two centres. PATIENTS: A total of 144 ventilated neonates. Inclusion criteria were postnatal age <3 days, ventilation <8 hours, and indwelling arterial line. Exclusion criteria were severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers. INTERVENTION: Arterial blood pressure was measured before the start and during the first 48 hours of masked infusion of drug (morphine/placebo; 100 microg/kg + 10 microg/kg/h). OUTCOME MEASURES: Arterial blood pressure and blood pressure variability. RESULTS: There were no significant differences in overall mean arterial blood pressure between the morphine group (median (interquartile range) 36 mm Hg (6) and the placebo group (38 mm Hg (6)) (p = 0.11). Although significantly more morphine treated patients (70%) showed hypotension than the placebo group (47%) (p = 0.004), the use of volume expanders and vasopressor drugs was not significantly different (morphine group, 44%; placebo group, 48%; p = 0.87), indicating the limited clinical significance of this side effect. Blood pressure variability was not influenced by routine morphine analgesia (p = 0.81) or additional morphine (p = 0.80). Patients with and without intraventricular haemorrhage showed no differences in blood pressure (Mann-Whitney U test 1953; p = 0.14) or incidence of hypotension (chi(2) test 1.16; df 1; p = 0.28). CONCLUSIONS: Overall arterial blood pressure, use of inotropes, and blood pressure variability were not influenced by morphine infusion. Therefore the clinical impact of hypotension as a side effect of low dose morphine treatment in neonates is negligible.     

Randomised double blind trial of morphine versus diamorphine for sedation of preterm neonates

AIMS—To compare the safety and effectiveness of morphine and diamorphine for the sedation of ventilated preterm neonates in a double blind, randomised trial.
METHODS—Eighty eight babies were allocated to receive either morphine (n = 44) or diamorphine (n = 44) by bolus infusion (200 or 120mcg/kg, respectively, over two hours), followed by maintenance infusion (25 or 15 mcg/kg/h, respectively) during the initial phase of their respiratory disease. Serial monitoring of physiological, behavioural, and biochemical variables over the first 24 hours of the infusions was performed. Longer term outcomes were also monitored.
RESULTS—Morphine, but not diamorphine, was associated with a mean (SEM) decrease in mean arterial blood pressure of 2.2 (1.0) mm Hg (p = 0.05) over the initial loading infusion. Physiological (blood pressure variability) and behavioural measures of sedation (clinical assessment and sedation scoring) indicated that the two drug regimens were equally effective after 24 hours, but the sedative effects of diamorphine were evident more quickly than those of morphine. Both regimens significantly reduced plasma adrenaline concentrations over the first 24 hours of the infusions. No significant differences in mortality, ventilator days, chronic lung disease or intracranial lesions were noted.
CONCLUSIONS—Both drug regimens reduce the stress response to ventilation in preterm neonates. However, diamorphine''s more rapid onset of sedation and morphine''s hypotensive tendency suggest that diamorphine is preferable for the sedation of mechanically ventilated preterm neonates.

     

Randomised controlled trial of low dose fentanyl infusion in preterm infants with hyaline membrane disease

AIM: To evaluate the effects of low dose fentanyl infusion analgesia on behavioural and neuroendocrine stress response and short term outcome in premature infants ventilated for hyaline membrane disease. METHODS: Twenty seven ventilated preterm infants were randomly assigned to receive a mean fentanyl infusion of 1.1 (0.08 SE) micrograms/kg/h for 75 (5) hours, and 28 untreated infants were considered a control group. A behavioural sedation score was used to assess the infants' behaviour. Urinary metanephrine and the normetanephrine:creatinine molar ratio were determined at 0, 24, 48 and 72 hours. Outcome data and ventilatory indexes were recorded for each infant. RESULTS: The fentanyl group showed significantly lower behavioural stress scores and O2 desaturations than controls and lower urinary concentrations of metanephrine and normetanephrine at 24, 48, 72 hours. The two groups showed no significant difference in ventilatory variables or short term outcome. CONCLUSIONS: A short course of low dose fentanyl infusion reduces behavioural sedation scores, O2 desaturations and neuroendocrine stress response in preterm ventilated infants.     

Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants

BACKGROUND: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. OBJECTIVES: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. METHODS: 11 patients (GA 26.6-33.0 weeks, BW 780-2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4-33.3 weeks, BW 842-1,955 g) were sedated with morphine (loading dose 0.05 mg/kg, maintenance 0.01 mg/kg/h). Changes in oxyhemoglobin (Delta cO2Hb) and deoxyhemoglobin (Delta cHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= Delta cO(2)Hb - Delta cHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (Delta ctHb = Delta cO2Hb + Delta cHHb) represent changes in cerebral blood volume (DeltaCBV). Changes in cerebral blood flow velocity (DeltaCBFV) were intermittently measured using Doppler ultrasound. Heart rate (HR), mean arterial blood pressure (MABP), arterial oxygen saturation (saO2) and transcutaneous measured pO2 (tcpO2) and pCO2 (tcpCO2) were continuously registered. Statistical analyses were carried out using linear mixed models to account for the longitudinal character study design. RESULTS: Within 15 min after the loading dose of midazolam, a decrease in saO2, tcpO2 and cHbD was observed in 5/11 infants. In addition, a fall in MABP and CBFV was observed 15 min after midazolam administration. Immediately after morphine infusion a decrease in saO2, tcpO2 and cHbD was observed in 6/10 infants. Furthermore, morphine infusion resulted in a persistent increase in CBV. CONCLUSIONS: Administration of midazolam and morphine in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful.     

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目的评价小剂量芬太尼持续滴注对机械通气早产儿的镇痛作用、神经行为以及短期预后的影响。方法2000年10月至2003年10月,将广东省妇幼保健院新生儿科行机械通气治疗的36例早产儿随机分为实验组与对照组,实验组18例早产儿滴注芬太尼,平均剂量为(1.10±0.06)μg/(kg·h),平均滴注时间为(65±5)h,对照组18例患儿,以相同滴注速度滴注注射用水。应用镇静行为评分评价患儿的镇静效果,并记录各患儿的通气指标以及预后数据。结果实验组的镇静行为评分显著低于对照组,2组的机械通气参数及短期预后无显著差异。结论短时间小剂量滴注芬太尼可降低机械通气的早产儿行为评分,并能取得良好的镇痛效果。     

Sedation with midazolam for voiding cystourethrography in children: a randomised double-blind study

BACKGROUND: Sedation with midazolam facilitates the performance of diagnostic procedures in children, including voiding cystourethrography (VCUG). However, the influence of sedation on voiding and imaging results have not been adequately evaluated. OBJECTIVE: Midazolam and placebo were compared to assess discomfort during VCUG and to evaluate if sedation influenced the outcome of the examination. MATERIALS AND METHODS: The study was prospective, randomised and double-blind, and included 95 children, 48 in the midazolam group (median age 2.2 years) and 47 in the placebo group (median age 3.2 years). The evaluation included the child's/parent's experience of the VCUG, as well as the examination results. RESULTS: The children/parents in the midazolam group experienced the VCUG as less distressing compared to those in the placebo group ( P<0.001). Forty-six of 48 children sedated with midazolam could void during the imaging procedure compared to 38 of 47 children given placebo ( NS). There was no difference in frequency or grade of vesicoureteric reflux or bladder emptying between the groups. CONCLUSIONS: When sedation is required to perform VCUG in children, midazolam can be used without negative effect on the outcome of the examination.     

Minimal ventilation to prevent bronchopulmonary dysplasia in extremely-low-birth-weight infants

OBJECTIVE: To determine whether minimal ventilation decreases death or bronchopulmonary dysplasia (BPD).Study design: Infants with birth weight 501 g to 1000 g and mechanically ventilated before 12 hours were randomly assigned to minimal ventilation (partial pressure of carbon dioxide [PCO(2)] target >52 mm Hg) or routine ventilation (PCO(2) target <48 mm Hg) and a tapered dexamethasone course or saline placebo for 10 days, using a 2 x 2 factorial design. The primary outcome was death or BPD at 36 weeks' postmenstrual age. RESULTS: After enrollment of 220 patients, the trial was halted because of unanticipated nonrespiratory adverse events related to dexamethasone therapy. The relative risk for death or BPD at 36 weeks in the minimal versus routine ventilation groups was 0.93 (95% CI, 0.77-1.12; P =.43). Ventilator support at 36 weeks was 1% in the minimal versus 16% in the routine group (P <.01). Major morbidities and long-term outcome were comparable in both treatment groups. CONCLUSIONS: With the sample size studied, minimal ventilation did not reduce the incidence of death or BPD. The reduced ventilator support at 36 weeks in the minimal ventilation group warrants further study of this intervention.     

Sedative tolerance accompanies tolerance to the analgesic effects of fentanyl in infant rats

Iatrogenic tolerance and physical dependence have been documented in human neonates and infants infused with fentanyl or morphine i.v. to maintain continuous analgesia and sedation during extracorporeal membrane oxygenation (ECMO) and mechanical ventilation for the treatment of life-threatening pulmonary diseases. Using postnatal d 17 infant rats, the hypothesis was tested that sedative tolerance accompanies tolerance to fentanyl analgesia in the tail-flick test. Postnatal d 14 infant rats remained naive or received osmotic minipumps infusing saline (1 microL/h) or fentanyl citrate (60 microg x kg(-1) h(-1)). Seventy-two hours later, fentanyl's antinociceptive potency was reduced 3.1-fold in fentanyl-infused rats. Conscious sedation and deep sedation were examined with the cliff-avoidance and the righting-reflex procedures, respectively. Fentanyl-infused infants were tolerant to both the conscious and deep sedative effects of fentanyl. Another hypothesis tested was that very high receptor intrinsic activity opioids are less likely to produce tolerance, or to be cross-tolerant to other opioids. Dihydroetorphine is 5,000 to 10,000 times more potent than morphine. However, fentanyl-infused infant rats were cross-tolerant to the analgesic and sedative effects of dihydroetorphine. Interestingly, dihydroetorphine's analgesic efficacy was significantly reduced to a maximum analgesic efficacy (Emax) value of 40% maximum possible effect (MPE). Another concern was whether fentanyl tolerance would generalize to another class of sedatives, the benzodiazepines. This was especially relevant considering the widespread use of benzodiazepines like midazolam in ECMO and mechanical ventilation. Midazolam elicited no analgesia in the tail-flick test. Furthermore, fentanyl-tolerant rats were not cross-tolerant to the conscious or deep sedative effects of midazolam.     

Use of dexmedetomidine in children after cardiac and thoracic surgery.

OBJECTIVE: In this report, we describe our experience with the use of dexmedetomidine in spontaneously breathing as well as in mechanically ventilated patients, after congenital cardiac and thoracic surgery. DESIGN: Retrospective case series. SETTING: University hospital, pediatric cardiac intensive care unit. PATIENTS: Thirty-three spontaneously breathing and five mechanically ventilated patients who received dexmedetomidine after cardiothoracic surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-eight patients, age 8 +/- 1.1 yrs old and weight 29 +/- 3.8 kg, were included. Seven patients (18%) were <1 yr old. Dexmedetomidine was used as a primary sedative and analgesic agent, and when its effect was considered inadequate, despite incremental infusion doses, a rescue agent was administered. The initial dexmedetomidine infusion dose was 0.32 +/- 0.15 microg/kg/hr followed by an average infusion of 0.3 +/- 0.05 microg/kg/hr (range 0.1-0.75 microg/kg/hr). There was a trend toward higher dexmedetomidine infusion requirement in patients <1 yr old compared with older children, 0.4 +/- 0.13 vs. 0.29 +/- 0.17 microg/kg/hr (p = .06). Desired sedation and analgesia were achieved during 93% and 83% of the dexmedetomidine infusion, respectively. According to the intensive care unit sedation scale (score 0-3) and two pain scales (Numeric Visual Analog Scale and Face, Legs, Activity, Cry, and Consolability, score 0-10), the mean sedation score was 1.3 +/- 0.6 (mild sedation) and the mean pain score was 1.5 +/- 0.9 (mild pain). The most frequently rescue drugs administered were fentanyl, morphine, and midazolam. Overall, 49 rescue doses of sedatives/analgesics were given. Patients <1 yr old required more rescue boluses than older children, 22 boluses (3.19 +/- 0.8) vs. 27 boluses (0.8 +/- 0.2, p = .003). Throughout the dexmedetomidine infusion there was no significant change in the systolic and diastolic blood pressure trend. Six patients (15%) had documented hypotension. In three, hypotension resolved with decreasing the dexmedetomidine infusion dose whereas in the other three, hypotension resolved after discontinuing the infusion. Although there was a trend toward lower heart rates, this was not clinically significant. One patient had an episode of considerable bradycardia without hypotension, which resolved shortly after discontinuing the dexmedetomidine infusion. No significant changes in the arterial blood gases or respiratory rates were observed. There was no mortality, and the total intensive care unit length of stay was 19 +/- 2 hrs. CONCLUSIONS: Our data suggest that dexmedetomidine is a well-tolerated and effective agent for both spontaneously breathing and mechanically ventilated patients following congenital cardiac and thoracic surgery.     

Clinical experience with continuous intravenous sedation using midazolam and fentanyl in the paediatric intensive care unit

Twenty-four patients in a paediatric intensive care unit mostly undergoing cardiac surgery, received a midazolam dosage between 50–400 g/kg per hour as a continuous intravenous infusion partly in combination with fentanyl [0,5–2,5 g/kg per hour] for analgesia and sedation. The mean duration of midazolam infusion was 11.6 days (range 38h–40 days). Blood samples for the HPLC assay of serum midazolam concentration were taken and the clearance estimated. The efficiency of sedation in correlation to the midazolam concentration was evaluated by a clinical sedation score. Serum midazolam concentrations between 100–400 g/l were sufficient for sedation. Dosage had to be increased during therapy according to an increased midazolam clearance. The evaluation of the sedation score showed that sedation of artifically ventilated infants and young children can be established by continuous intravenous infusion of midazolam.Dedicated to the 65th birthday of Prof.Dr. Erich Gladtke     

Sedation and monitoring of paediatric patients undergoing open low-field MRI

The purpose of this study was to determine the need, effectiveness and safety of sedation and monitoring in infants and children in a paediatric open low-field MRI system. Of 274 patients (median age 9 y) examined, only 74 children (median age 25 mo) needed sedation. Sedation was achieved by intravenous administration of midazolam (0.2 mg/kg) and etomidate (0.2 mg/kg). Mean total doses required were 0.28 and 0.27 mgl/kg, respectively. With the exception of eight primarily ventilated patients, all children breathed spontaneously. O2 saturation, arterial blood pressure and ECG were monitored. The low resonance frequency of the MRI system required a specially designed high frequency (HF) shielding of the monitor system to avoid HF artifacts. The overall sedation rate was markedly lower (74/274 = 27%) compared to a control group previously examined in a closed high-field MRI system (52/111 = 47%). This was due to a significant lower need for sedation in patients aged up to 10 y (p < or = 0.0001) in the open MRI unit. General anaesthesia could be avoided in all patients. No significant movement artifacts occurred in any of the MRI examinations and no serious side effects were observed. CONCLUSIONS: MRI of children is easier in an open MRI system and with fewer sedations, as in closed high-field systems. Sedation by a combination of midazolam and etomidate is highly effective and safe. Monitoring devices for high-field systems may have to be modified for low-field systems. An in-house paediatric MRI unit with an open and special paediatric design is of major advantage for imaging paediatric patients.     

咪达唑仑滴鼻用于新生儿磁共振镇静的效果研究——前瞻性单盲随机对照研究

目的 观察并比较咪达唑仑经鼻吸收与苯巴比妥钠肌肉注射对于新生儿头颅磁共振检查时的镇静效果。方法 将2017年9月至2019年3月间行头颅磁共振检查的70例新生儿随机分为观察组和对照组，每组35例。观察组给予咪达唑仑滴鼻（0.3 mg/kg），对照组给予苯巴比妥钠肌肉注射（10 mg/kg）。应用改良Ramsay镇静评分表评估新生儿镇静情况；同时比较两组磁共振完成情况及不良反应发生情况。结果 观察组给药后20 min时镇静评分最高，后逐渐降低，70 min时降至最低；对照组给药后10 min时镇静评分最低，后逐渐增高，40 min、50 min时达最高，再逐渐降低。两组各时间段镇静评分比较，给药后40 min前观察组镇静评分均高于对照组（P < 0.05）；40~70 min两组镇静评分比较差异均无统计学意义（P > 0.05）。观察组磁共振检查成功率（89%）高于对照组（69%，P < 0.05）。两组不良反应比较，差异无统计学意义（P > 0.05）。结论 咪达唑仑滴鼻用于新生儿头颅磁共振检查的镇静效果优于苯巴比妥钠肌肉注射，且快速易行，安全有效。     

Clara cell secretory protein (CC16) as a peripheral blood biomarker of lung injury in ventilated preterm neonates

The aim of this study was to assess the serum concentrations of Clara cell secretory protein (CC16) in association with acute and chronic lung injury in mechanically ventilated preterm neonates. Thirty-five preterm neonates (gestational age [GA] ≤31 weeks) with acute respiratory failure were enrolled. Of these, 23 neonates requiring ventilatory support within 2 h after birth comprised the mechanically ventilated group (MV group), and 12 neonates who were not ventilated made up the nonventilated group (NV group). Serum CC16 was measured (using enzyme-linked immunosorbent assay [ELISA]) within 2 h (T0) and at 72 h (T1) after birth, at day 14 of life (T2) and at 36 weeks postmenstrual age (T3). The median CC16 concentrations were significantly higher in the MV group compared to the NV group at all times. Analysis with respect to differences observed in the group characteristics showed that GA, Apgar score at 5 min and mechanical ventilation were significant covariates of serum CC16 at T0. All neonates in the NV group and 18 cases in the MV group, respectively, survived discharge. Ventilated survivors with later bronchopulmonary dysplasia (BPD; oxygen requirement at T3, n = 7) had significantly higher CC16 at all times compared to nonventilated neonates. Elevated serum CC16 levels at T2 were predictive of BPD development. In conclusion, our results show that serum CC16 increases significantly in preterm neonates ventilated early after birth and remains high in those with later BPD. Further research is needed to validate the usefulness of CC16 as a peripheral blood biomarker of acute and chronic lung injury.     

Haemodynamic features during high-frequency oscillatory ventilation in preterms

Aim: To compare the haemodynamic status during high-frequency oscillatory ventilation and conventional mechanical ventilation in very preterm infants with respiratory distress syndrome. Methods: Thirty-two neonates of less than 30 wk gestation randomly assigned to high-frequency oscillatory ventilation (n = 15) or conventional mechanical ventilation (n = 17) had three echocardiographies and one cerebral Doppler-echography under the same ventilation during the first 48 h of life. Results: Mean airway pressure was 2 cm H[Formula: See Text]O higher in infants ventilated with high-frequency oscillatory ventilation at the different echocardiographies. Comparable right ventricular indexes were observed in the two groups. Reduction of the ductus arteriosus diameter and ductal closure were significant only in neonates ventilated conventionally. Left ventricular performance and left ventricular contractility did not differ between the groups. The high-frequency group had lower end diastolic velocity and a higher resistance index in the anterior cerebral artery.

Conclusion: Compared with conventional mechanical ventilation, high-frequency oscillatory ventilation was achieved without altering cardiac function. However, the inability of the left ventricle to improve its performance in the presence of a significant ductal shunt suggests a narrow range of optimal pressures under this ventilatory mode.     

山东省多中心儿童重症监护室镇静镇痛治疗及管理状况调查

目的了解山东省三级甲等医院儿童重症监护室(PICU)镇静镇痛治疗及管理状况,为镇静镇痛治疗方案的改进提供依据。方法本研究为一项多中心回顾性研究,山东省6家三级甲等医院的PICU参与了本研究。收集2016年1月至2018年12月入住这6家PICU的1340例患儿,调阅病历资料,统计患儿的年龄、性别、入院24 h小儿死亡风险评分Ⅲ、是否接受机械通气、是否接受镇静和(或)镇痛治疗、是否监测镇静和(或)镇痛情况、住院病死率等。依据是否接受镇静治疗和(或)镇痛治疗,将患儿分为单纯镇静组(798例)、镇静+镇痛组(120例)及非镇静镇痛组(422例),比较各组的病种、机械通气比例、低血压发生率、平均住PICU天数及院内病死率。结果1340例患儿的平均年龄为(13.3±6.4)个月,其中男786例(58.7%)。6家PICU均已开展镇静治疗,其中5家PICU进行常规镇静评估;已开展镇痛治疗的PICU有4家,其中仅有2家进行常规疼痛评估。共有918例(68.5%)患儿接受了镇静治疗和(或)镇痛治疗,咪达唑仑是最常用的镇静药物,其次是右美托咪定。526例(57.3%)患儿进行了镇静评估监测,最常用的评估方法是Richmond躁动镇静量表。120例(9.0%)患儿接受了镇静联合镇痛治疗,芬太尼是最常用的镇痛药物,38例(31.7%)患儿接受了常规疼痛评估。3组患儿年龄和性别差异无统计学意义。镇静+镇痛组外科疾病的比例最高,该组机械通气患儿的比例也最高(100.0%,120/120),非镇静镇痛组机械通气患儿的比例最低(11.4%,48/422),两组比较差异有统计学意义(P<0.01)。镇静+镇痛组的平均机械通气时间略短于单纯镇静组,但组间比较差异无统计学意义(P>0.05)。镇静+镇痛组低血压发生率最高,非镇静镇痛组低血压发生率最低[21.7%(26/120)比2.1%(9/422),P<0.01]。院内病死率和平均住PICU天数3组间比较差异无统计学意义。结论苯二氮类药物仍是目前山东省PICU中主要使用的镇静药物,右美托咪定的应用逐渐增加,但镇痛剂应用的比例很低。目前镇痛镇静治疗主要用于外科术后及接受机械通气治疗的患儿,镇痛镇静治疗虽未增加患儿的院内病死率及平均住PICU天数,但增加了低血压的发生率。山东省PICU的镇静镇痛治疗和监测仍欠规范,主要体现在镇痛治疗以及对镇静和疼痛水平的评估未受到重视。     

Predictors of fatality in neonates requiring mechanical ventilation

OBJECTIVE: To evaluate initial arterial blood gas, pulmonary pressures, pulmonary mechanics (compliance and resistance), pulmonary volumes, oxygenation indices and serum carotenoid levels as predictors of fatality in mechanically ventilated neonates. DESIGN: Cross Sectional. SETTING: Referral neonatal unit of a teaching hospital. SUBJECTS: 83 mechanically ventilated outborn neonates. METHODS: 83 neonates consecutively put on mechanical ventilator from March to December 2001 were enrolled in the study. The mechanical ventilator used was pressure limited time cycled ventilator with facility for online measurement of volumes and pulmonary mechanics. Arterial blood gas after half an hour of initiation of mechanical ventilation and initial pulmonary pressures, pulmonary compliance, resistance and duration of mechanical ventilation were recorded in a pre structured proforma. Initial serum carotenoid levels were also measured using spectrophotometric method. The neonates were regularly followed up for outcome. Multiple logistic regression analysis was done to find out the predictors of fatality for those variables that were significantly associated with outcome on univariate analysis. RESULTS: On univariate analysis weight ( < 2000 g), gestational age <34 weeks, pH <7.3, duration of mechanical ventilation <72 hours, a/A <0.25, compliance <1 mL/cmH2O, fraction of inspired oxygen (FiO2) >60%, oxygenation index >10, AaDO2 >250 and serum carotenoid levels < 100 microg/dL were significantly associated with fatality in neonates requiring mechanical ventilation. However, on multiple regression analysis only FiO2, gestational age and serum carotenoids < 100 microg/dL were found to be independent predictors of fatality. CONCLUSIONS: Initial FiO2 > 60%, gestational age <34 weeks and initial serum carotenoid levels < 100 microg/dL were independent predictors of fatality in neonatal mechanical ventilation. Even in a setting with high fatality rates, high risk of mortality in mechanically ventilated neonates can be identified.     

Protective effect of pentoxifylline on volume-induced lung injury in newborn piglets

To evaluate the efficacy of pentoxifylline (PTXF) in the attenuation of lung inflammation during volume-induced lung injury (VILI) in newborn piglets, 17 newborn piglets were mechanically ventilated with a large tidal volume (50 ml/kg) for a period of 8 h. They were randomly assigned to a placebo (PL, n = 9) or a treatment group (PTXF, n = 8) that received PTXF (20 mg/kg as a bolus, followed by a continuous infusion of 5 mg/kg/h). Hemodynamics, lung mechanics and arterial blood gases were measured during the 8 h of study. Serum and tracheoalveolar fluid (TAF) platelet-activating factor (PAF) and thromboxane (TXB(2)) levels were obtained at baseline and at 8 h, while lung tissue myeloperoxidase (MPO) and wet to dry weight were assessed after the completion of the study. In the PL group, a marked increase in TAF PAF and TXB(2) levels was observed only in TAF, suggesting that the inflammatory process was localized within the lungs. A significant decrease in lung tissue MPO activity (p < 0.005) and lung wet to dry weight ratio (p < 0.04) was observed in the PTXF group. There were no differences in hemodynamics, arterial blood gases or lung mechanics measurements between groups. A significant reduction in pulmonary inflammatory response was observed during VILI in the PTXF pretreated animals. These results suggest that PTXF may be effective in modulating lung inflammation associated with mechanical ventilation in neonates.     

Evaluation of intranasal midazolam in refraction and fundus examination of young children with strabismus

PURPOSE: To determine the clinical sedative effect and dosage of intranasal midazolam in refraction and fundus examination of children with strabismus. PATIENTS AND METHODS: Refraction and fundus examination with (n = 28) and without (n = 24) sedation were performed in 52 children with strabismus whose ages ranged from 7 to 26 months. We delivered a 5-mg/mL solution of midazolam via a syringe for 60 seconds to provide a dose of 0.2 mg/kg. We repeated the dose to a maximum of 0.3 mg/kg if there was no clinical sedative response after 10 to 15 minutes. The ease of examination and sedation for each patient was scored by a blinded observer. The groups were evaluated for ease of examination and the time needed to complete it. RESULTS: We obtained clinically adequate sedation at a mean (+/- standard deviation) of 15 minutes (+/- 2.69 minutes). Sedation was achieved with a mean dose of 2.64 mg/kg (+/- 0.66 mg/kg). Children receiving midazolam had significantly calmer examination scores. The time needed to complete the examination was statistically significantly shorter for these children than for children not receiving sedation (P < .05). CONCLUSIONS: Intranasal midazolam is a beneficial drug and method of delivery for the sedation of anxious children with strabismus undergoing refraction and fundus examination. Sedation prior to examination is effective in reducing the anxiety and time associated with ophthalmologic examination of children with strabismus.