Respiratory muscle rigidity in a preterm infant after use of fentanyl during Caesarean section

Fentanyl is in many neonatal intensive care units the sedative of choice. One side-effect is, however, the possibility of muscle and/or chest wall rigidity. A pregnant woman with a critical pulmonary valve stenosis had a balloon dilatation at 26 weeks of gestation. She was put on propranolol, but went into a severe cardiac failure. In week 31, she developed pregnancy induced hypertension. Periodically absent diastolic flow in the umbilical cord was demonstrated. A Caesarean section was performed using fentanyl as analgesia. A boy weighing 1440 g, had a 1 min Apgar score of 3 without respiratory movements. Mask ventilation was tried, but chest wall expansion was not achieved despite using high pressures. He was intubated and positive pressure ventilation attempted, with the same result. Despite the use of high pressures up to 60–70 cm H₂O, no chest movement could be achieved. An intravenous line was established in order to give naloxone and pancuronium. Just before the drugs were given, chest wall movements were achieved and the heart rate normalized. Conclusion This is the first report on chest wall rigidity in a neonate after administration of fentanyl to the mother during Caesarean section. Received: 15 August 1997 and in revised form 30 January 1998 / Accepted 3 February 1998     

Buprenorphine substitution ameliorates spontaneous withdrawal in fentanyl-dependent rat pups

Iatrogenic physical dependence has been documented in human infants infused i.v. with fentanyl or morphine to maintain continuous analgesia and sedation during extracorporeal membrane oxygenation and mechanical ventilation. Many infants are slowly weaned from the opioid. However, this approach requires extended hospital stays. Little is known about the potential benefits of substitution therapy to prevent abstinence. Therefore, the hypothesis was tested that s.c. and p.o. buprenorphine substitution would ameliorate spontaneous withdrawal in fentanyl-dependent rat pups. Analgesia in the tail-flick test was used to indicate behaviorally active doses of buprenorphine in opioid-na?ve postnatal day 17 rats. Other postnatal day 14 rat pups were surgically implanted with osmotic minipumps that infused saline (1 microL/h) or fentanyl (60 microg/kg/h) for 72 h. Vehicle or buprenorphine was administered s.c. or p.o. before the initiation of spontaneous withdrawal brought about the removal of the osmotic minipumps. The major withdrawal signs of wet-dog shakes, jumping, wall climbing, forepaw tremor, and mastication were counted during a 3-h period of withdrawal. The major scored sign, scream on touch, was assessed every 15 min for 3 h. Injection of naloxone after the 3-h observation did not reveal any residual dependence. Subcutaneous buprenorphine administration significantly ameliorated all signs of withdrawal. Surprisingly, p.o. buprenorphine was nearly as efficacious as the s.c. route of administration. These results indicate that buprenorphine substitution therapy may be effective in fentanyl-dependent human infants.     

Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports

Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.     

The effect of gavage feeding on the mechanics of the lung, chest wall, and diaphragm of preterm infants

Preterm infants when given bolus nasogastric (gavage) feedings have well-characterized decreases in arterial partial pressure of oxygen, increases in arterial partial pressure of carbon dioxide, a tendency to have apnea, and are reported to have no change in the mechanics of breathing. The purpose of this study was to assess the function of the lungs, chest wall, and diaphragm in preterm infants without lung disease before and after gavage feeding. Lung mechanics were measured with a pneumotachograph and esophageal balloon, and the mechanics of the chest wall and diaphragm were assessed by inductance plethysmography and measurement of transdiaphragmatic pressure. After feeding, there was a significant decrease in dynamic lung compliance and increase in the minute ventilation (p less than 0.05). The work performed on the lungs was unchanged. The chest wall became more stable, with a significant decrease in its dynamic compliance (p less than 0.05). The diaphragmatic volume displacement, expressed as a percentage of the minute ventilation, was unchanged. The diaphragmatic work increased significantly (p less than 0.05), and was greater than four times the work performed on the lungs. These results are consistent with previous reports of a decrease in functional residual capacity after feeding. The mechanical stability of the chest wall may have been improved by an increase in the area of apposition of the diaphragm to it, or by an increase in the central drive to breathing after feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

新型鼻塞持续气道正压与肺表面活性物质治疗新生儿呼吸窘迫综合征疗效观察

目的　探讨新型鼻塞持续气道正压通气 (NCPAP)与肺表面活性物质 (PS)联合应用治疗新生儿呼吸窘迫综合征 (NRDS)的疗效及临床价值。方法　对 2 3例NRDS患儿进行NCPAP通气同时给予PS治疗 ,观察治疗前后血气、X线胸片和临床效果。结果　与用药前相比 ,用药后 0 5h ,PaO2 和a/APO2 即明显升高。至 6、12、2 4和 72h ,PaO2 和a/APO2 仍高于用药前水平 ,有显著性差异 (P均 <0 0 1)。用药后 6h ,PaCO2 开始下降 ,6、12、2 4和 72h ,PaCO2 明显下降 ,有显著性差异 (P均 <0 0 1)。用药后 1h ,呼吸窘迫症状消失 9例 (39 1% ) ;明显减轻 14例 (6 0 9% )。 2 4h后 ,X胸片显示肺野透明度明显改善 2 2例 (95 7% )。 2 3例中治愈 2 2例 ,治愈率 95 7%。 1例改为机械通气。结论　NCPAP与PS联合治疗NRDS疗效显著 ,能快速有效地改善NRDS的肺换气和通气功能 ,可节省PS及减少机械通气率     

Cerebral blood flow in preterm infants during the first week of life

Forty-two preterm infants of 28-33 weeks of gestation were studied once during the first week of life by 133-Xenon clearance after intravenous injection to estimate global cerebral blood flow. Count rates detected over the chest were corrected for chest wall contribution and used as arterial input function. A neonatal blood-brain partition coefficient of Xenon was used for the calculation of a mean flow estimator (CBF-infinity). The technique was internally validated by use of differently obtained arterial input functions. In 11 infants without respiratory distress, CBF-infinity was 19.8 ml/100 g/min +/- 5.3 SD. In 24 infants treated with mechanical ventilation CBF-infinity was 11.8 ml/100 g/min +/- 3.2 SD. In 7 infants treated with continuous positive airway pressure CBF-infinity was 21.3 ml/100 g/min +/- 12.0 SD. When the reduction of CBF-infinity associated with mechanical ventilation was taken into account, the 9 infants with subependymal/intraventricular haemorrhage had increased CBF-infinity. The effects of gestational age, birthweight, mode of delivery, postnatal age, mean arterial blood pressure, PaCO2, blood haemoglobin and phenobarbitone medication were also analysed and found inconsistent. In conclusion, CBF was lower than expected and in infants requiring mechanical ventilation the values were lower still.     

Cerebral Blood Flow in Preterm Infants during the First Week of Life

ABSTRACT. Forty-two preterm infants of 28–33 weeks of gestation were studied once during the first week of life by 133-Xenon clearance after intravenous injection to estimate global cerebral blood flow. Count rates detected over the chest were corrected for chest wall contribution and used as arterial input function. A neonatal blood-brain partition coefficient of Xenon was used for the calculation of a mean flow estimator (CBF-∞). The techique was internally validated by use of differently obtained arterial input functions. In 11 infants wihout respiratory distress, CBF-∞ was 19.8 ml/100 g/min ±5.3 SD. In 24 infants treated with mechanical ventilation CBF-∞ was 11.8 ml/100 g/min ±3.2 SD. In 7 infants treated with continous positive airway pressure CBF-∞ was 21.3 ml/100 g/min ±12.0 SD. When the reduction of CBF-∞ associated with mechanical ventilation was taken into account, the 9 infants with subependymal/intraventricular haemorrhage had increased CBF-∞. The effects of gestational age, birthweight, mode of delivery, postnatal age, mean arterial blood pressure, PaCO2, blood haemoglobin and phenobarbitone medication were also analysed and found inconsistent. In conclusion, CBF was lower than expected and in infants requring mechanical ventilation the values were lower still.     

Effects of inspiratory resistive loading on chest wall motion and ventilation: differences between preterm and full-term infants.

The ability to maintain effective tidal volume and minute ventilation during resistive loaded breathing depends on both adequate central neural respiratory output response and respiratory system mechanical properties such as respiratory muscle strength and chest wall stability. We hypothesized that chest wall instability limits the ability of the preterm (PT) infant to respond to inspiratory resistive loading (IRL) compared with full-term (FT) infants. To test this hypothesis, we subjected eight FT and 10 PT infants to IRL with loads of 1.3, 2, and 6 times intrinsic lung resistance and measured steady state tidal volume (VT), minute ventilation (VE), and chest wall motion. Thoracoabdominal asynchrony was measured by respiratory inductive plethysmography and quantitated by measuring the phase angle, theta, between rib cage and abdominal motion (0 degrees = synchronous motion, 180 degrees = paradoxic motion). At baseline, VT/kg (mL/kg, mean +/- SEM) was similar between PT (7.0 +/- 0.7) and FT (7.5 +/- 0.5) infants. VE/kg (mL/min/kg) was greater in PT (545 +/- 50) than in FT (385 +/- 33) infants (p < 0.05) as a result of increased respiratory frequency in the former. PT infants demonstrated significantly greater chest wall asynchrony (theta = 38 +/- 9 degrees) than FT infants (theta = 9 +/- 3 degrees) (p < 0.01). With the highest resistive loads, VT decreased significantly in the PT but not the FT infants. Furthermore, during IRL, VE decreased to 417 +/- 50 mL/min/kg (p < 0.05) and theta increased to 56 +/- 7 (p < 0.05) in the PT infants, whereas no significant change in either value was observed in the FT group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of chest physiotherapy on pO2 and pCO2 in premature and mature babies with respiratory distress syndrome (author's transl)]

pH, pCO2, pO2 and where possible DAaO2 determinations were done before, immediately after and 30 minutes after chest physiotherapy in 4 groups (respiratory adaptation disturbance, pneumonia, hyaline membrane disease--controlled ventilation and RDS--nasal-CPAP) of mature and premature infants and in a group of healthy infants. The most striking alterations of the parameters investigated were found in infants treated with nasal-CPAP and controlled ventilation where especially a decrease of pH and increase of pCO2 was observed. After small increases of paO2 immediately after physiotherapy the paO2 values and concomitantly DAaO2 values 30 minutes after chest physiotherapy fell below the levels before physiotherapy. There was no significant change from pretreatment values in any group of infants. A physiotherapist experienced in the care of infants with respiratory diseases is most important for achieving satisfactory results.     

早产儿呼吸窘迫综合征的呼吸支持策略及研究进展

新生儿呼吸窘迫综合征（respiratory distress syndrome,RDS）多见于早产儿,胎龄越小,发病率越高。近年的大规模随机对照研究突出了产房内开始的持续气道正压通气（continuous positive airway pressure,CPAP）在RDS防治中的重要作用,对于生后有自主呼吸的早产儿,产房内应用CPAP优于气管插管,而顶防性应用肺表面活性物质（pulmonary surfactant,PS）不再具有优势。2013版欧洲新生儿RDS防治指南推荐有患RDS风险的早产儿生后均应立即接受CPAP支持,初设呼气末正压至少6cmH2O（1cmn20=0．098kPa）;对于患RDS的早产儿,最理想的处理是生后CPAP以及早期解救性PS应用。而需要气管插管的早产儿应尽早接受PS替代治疗。不能耐受CPAP的患儿更换通气模式为无创正压通气可能降低拔管失败率。目前有多种策略来缩短机械通气时间并增加无创通气的成功率。患RDS的极早产儿应常规接受咖啡因治疗以提高撤机成功率,并降低支气管肺发育不良的发生率。生后1～2周后仍不能脱离呼吸机者,需接受小剂量递减地塞米松治疗,但应避免生后1周内应用地塞米松以及较大剂量应用。     

极/超早产儿的生存现状和呼吸管理进展

极/超早产儿由于肺发育不成熟,病死率和支气管肺发育不良的发生率较高,呼吸管理和患儿的生存率及生存质量密切相关.合理的产前皮质激素促肺成熟、肺表面活性物质(pulmonary surfactant,PS)的应用和机械通气策略有助于改善极/超早产儿的预后.采用无创技术进行呼吸支持,特别是生后立即给予持续气道正压通气而后根据病情选择性给予PS作为预防性给予PS的替代呼吸支持策略已受到普遍推荐.新的机械通气策略与模式如高频振荡通气、神经调节辅助呼吸和目标容量通气是否具有更大的优势仍需要进一步的研究证实.     

肺表面活性剂治疗对新生儿呼吸窘迫综合征肺功能影响的研究

目的观察肺表面活性剂(PS)对新生儿呼吸窘迫综合征(NRDS)肺功能的影响.方法用PS固尔舒治疗10例NRDS患儿.观察治疗前后血气、肺泡充气程度和胸肺总有效动态顺应性的变化.结果用药后30min,PO2和动脉-肺泡氧分压比值(a/APO2)与用药前比较明显升高,用药后1、6、12、24h和3天,PO2和a/APO2仍高于用药前水平,差异均有显著意义(均为P＜0.05).用药后6h,PCO2显著下降,12、24h和3天,PCO2进一步下降,与用药前比较,差异均有显著意义(均为P＜0.05).用药后6h,胸肺总有效动态顺应性较用药前明显升高(P＜0.05),12和24h仍在较高水平,与用药前比较,均为P＜0.01.同时,X线胸片显示肺野透亮度明显改善.结论PS固尔舒能有效改善NRDS的肺换气和通气功能、肺泡充气程度以胸肺总有效动态顺应性.     

Effect of supine and prone positions on arterial oxygen tension in the preterm infant.

To determine the optimal position for the preterm infant, arterial oxygen tension (Pao2) was monitored in 16 preterm infants by the transcutaneous method with the infants in both supine and prone positions. When the infants were prone, Pao2 rose by a mean of 7.4 mm Hg (P less than .001), an increase of 15%. In those infants with residual cardiopulmonary disease a 25% increase was noted. The higher Pao2 in the prone position was accompanied by a significant decrease in the amount of time the chest wall moved asynchronously. This improved oxygenation in the prone position appears to be the result of enhanced ventilation/perfusion ratios and not merely secondary to an alteration in sleep state with positioning of the infant. These findings may have important implications in the management of preterm infants, requiring neonatal intensive care.     

Reversible neurologic abnormalities associated with prolonged intravenous midazolam and fentanyl administration

An encephalopathy developed in three infants in the intensive care unit after heavy sedation with midazolam and fentanyl for 4 to 11 days. The affected infants had poor social interaction, decreased visual attentiveness, dystonic postures, and choreoathetosis. Symptoms cleared completely in 5 days to 4 weeks. Retrospective review of records of all children treated in the intensive care unit with prolonged intravenous administration of midazolam revealed that 45 children could be assessed neurologically on withdrawal of sedation. Three children had definite and two had possible neurologic sequelae (5/45, 11.1%). All had received concomitant intravenous fentanyl therapy. Neurologic sequelae were significantly associated with young age, female gender, low serum albumin concentration, and concomitant administration of aminophylline. This encephalopathy may represent a benzodiazepine withdrawal syndrome, a prolonged agonist action on the benzodiazepine receptor, or the combined effects of multiple toxic, metabolic, and infectious insults to the central nervous system of infants in the intensive care unit. Prolonged use of intravenous midazolam sedation necessitates careful dosing, monitoring, and discontinuation, particularly in infants and young children.     

小剂量芬太尼在机械通气中的应用

目的　 了解机械通气患儿以小剂量芬太尼持续静脉滴注的作用。 方法 　观察用药前后呼吸顺应性 (Cdyn)、气道阻力 (Raw)及呼气末二氧化碳分压 (PetCO2 )的变化。 结果 　 1个月～ 3岁患儿用药前后Raw及PetCO2 明显下降 ,肺部感染患儿指标变化显著大于非感染患儿 ,Cdyn用药前后均未发现显著差异。 结论 　提示机械通气中用小剂量芬太尼可以减轻人机对抗 ,降低气道压 ,改善肺气体交换及肺功能 ,有利于患儿顺利地渡过危险期     

Symptomatic patent ductus arteriosus following prophylactic indomethacin. A clinical and biochemical appraisal.

Seven of 36 premature infants with birth weight less than 1,250 g who had been randomly assigned to either high-frequency ventilatory ventilation or conventional mechanical ventilation developed symptomatic patent ductus arteriosus (PDA) after receiving prophylactic indomethacin, 0.2 mg/kg, i.v. 24 h after birth. Infants who developed symptomatic PDA were more likely to be white and male and have more severe pulmonary insufficiency than infants who did not develop symptomatic PDA. Serum indomethacin levels were similar in both groups of patients. There was no difference in the degree of suppression or subsequent recovery of endogenous eicosanoid biosynthesis between infants who did and did not develop symptomatic PDA. Compared to conventional mechanical ventilation, high-frequency oscillatory ventilation had no significant effect on endogenous eicosanoid biosynthesis. The susceptibility of white male infants to symptomatic PDA following prophylactic indomethacin may represent the influence of maturational factors on ductus patency. Cyclooxygenase products do not appear to be involved in mediating ductus patency when symptomatic PDA occurs immediately following administration of prophylactic indomethacin.     

芬太尼在机械通气新生儿镇痛中的临床应用分析

目的 探讨芬太尼对机械通气新生儿的镇痛效果及安全性。方法 将2010 年12 月至2011 年2月接受机械通气的30 例新生儿随机分为芬太尼组和对照组,每组均为15 例,两组除常规治疗外,芬太尼组加用芬太尼镇痛治疗。记录两组患儿在用药前及用药后30 min、2 h、4 h 的心率、呼吸频率、血压的变化及PIPP评分。患儿出院后进行随访,分别在3、6、9 和12 月龄时用CDCC 婴幼儿智能发育量表测定两组患儿智力发育指数(MDI)和精神运动发育指数(PDI)。结果 芬太尼组使用芬太尼后,其呼吸频率和心率均较对照组下降(PPP>0.05)。结论 芬太尼能有效缓解机械通气患儿的疼痛反应,且对患儿远期神经发育情况无影响。     

Effects of theophylline on ventilatory response to hypoxic challenge.

The respiratory and arousal responses to mild hypoxia during quiet sleep were studied using inductive plethysmography and transcutaneous gas electrodes in 11 apnoeic infants before and after the administration of oral theophylline (3 mg/kg). Theophylline changed the ventilatory response to a more biphasic pattern--that is, ventilation decreased after an initial increase. The relative ventilatory slope (defined as the decrease in transcutaneous carbon dioxide tension (PCO2) in relation to the fall in transcutaneous oxygen tension (PO2)) decreased significantly after theophylline. Four infants were roused during hypoxia before theophylline administration compared with none after treatment. Theophylline abolished the periodic breathing induced by hypoxia in one of six infants. These findings suggest that methylxanthines may not, as previously thought, enhance the respiratory drive during hypoxia.     

Monitoring of Regional Lung Ventilation Using Electrical Impedance Tomography After Cardiac Surgery in Infants and Children

Electrical impedance tomography (EIT) is a noninvasive method to monitor regional lung ventilation in infants and children without using radiation. The objective of this prospective study was to determine the value of EIT as an additional monitoring tool to assess regional lung ventilation after pediatric cardiac surgery for congenital heart disease in infants and children. EIT monitoring was performed in a prospective study comprising 30 pediatric patients who were mechanically ventilated after cardiac surgery. Data were analyzed off-line with respect to regional lung ventilation in different clinical situations. EIT data were correlated with respirator settings and arterial carbon dioxide (CO₂) partial pressure in the blood. In 29 of 30 patients, regional ventilation of the lung could sufficiently and reliably be monitored by means of EIT. The effects of the transition from mechanical ventilation to spontaneous breathing after extubation on regional lung ventilation were studied. After extubation, a significant decrease of relative impedance changes was evident. In addition, a negative correlation of arterial CO₂ partial pressure and relative impedance changes could be shown. EIT was sufficient to discriminate differences of regional lung ventilation in children and adolescents after cardiac surgery. EIT reliably provided additional information on regional lung ventilation in children after cardiac surgery. Neither chest tubes nor pacemaker wires nor the intensive care unit environment interfered with the application of EIT. EIT therefore may be used as an additional real-time monitoring tool in pediatric cardiac intensive care because it is noninvasive.     

PULMONARY MECHANICS, CHEST X-RAY AND LUNG DISEASE AFTER MECHANICAL VENTILATION IN LOW BIRTH WEIGHT INFANTS

Abstract. Lindroth, M., Jonson, B., Svenningsen, N. W. and Mortensson, W. (Neonatal Unit, Department of Paediatrics, University Hospital, Lund, Sweden). Pulmonary mechanics, chest X-ray and lung disease after mechanical ventilation in low birth weight infants. Acta Paediatr Scand, 69:761, 1980.—Pulmonary mechanics, chest X-ray and the incidence of clinical lung disease were studied in 41 low birth weight infants treated with intermittent positive pressure ventilation (IPPV) in the neonatal period. Shortly after IPPV most patients, irrespective of X-ray findings, had signs of lung damage reflected in low dynamic compliance or high pulmonary resistance. Both parameters, however, had a strong tendency towards normalization during the first year of life. Overdistention on chest X-ray was common at 6–12 months of age. Pneumonia and bronchitis were common during the first two years of life but subsided later on. Development of BPD or later respiratory disease were not correlated to treatment with high inspired oxygen concentrations but commonest in patients with hyaline membrane disease. The combined findings of pulmonary mechanics and chest X-ray shortly after IPPV were correlated to later clinical lung disease.