Paracetamol and Preterm Infants: a painless liaison?

__Abstract__ In the late 1980s there was a true turnabout on the important issue of neonatal pain. Then, Anand and co-workers [1, 2], published a trial on preterm infants randomly allocated to fentanyl with a muscle relaxant or muscle relaxant only during surgical patent ductus arteriosus (PDA) closure. This provided evidence, for the first time, that preterm infants have a capacity to feel pain from a very early age (24-26 weeks gestation) and that early repetitive pain gives rise to short-term and long-term consequences [3, 4]. Nowad

Eight years later, are we still hurting newborn infants?

Objective: To study whether new pharmacological and nonpharmacological guidelines lowered numbers of painful procedures in neonates and changed the amount and frequency of analgesic therapy as compared to the results of our previous study in 2001. Design: A prospective observational study. Setting: Level III NICU of the Erasmus MC-Sophia Children's Hospital, Rotterdam. Participants: Neonates admitted at postnatal ages less than 3 days with length of stay at least 72 h. Main Outcome Measures: Number of all potentially painful procedures and analgesic therapy recorded at the bedside during the first 14 days of NICU stay. Results: A total number of 21,076 procedures were performed in the 175 neonates studied during 1,730 patient-days (mean 12.2). The mean number of painful procedures per neonate per day was 11.4 (SD 5.7), significantly lower than the number of 14.3 (SD 4.0) in 2001 (p < 0.001). The use of analgesics was 36.6% compared to 60.3% in 2001. Sixty-three percent of all peripheral arterial line insertions failed versus 37.5% in 2001 and 9.1% venipunctures failed versus 21% in 2001. Conclusions: The mean number of painful procedures per NICU patient per day declined. Nonpharmacological pain- or stress-reducing strategies like NIDCAP and sucrose were fully embedded in our pain management. As further reduction of the number of painful procedures is unlikely, we should apply more nonpharmacological interventions and explore newer pharmacological agents

Insufficient Sedation and Severe Side Effects after Fast Administration of Remifentanil during INSURE in Preterm Newborns

Background: Neonatal intubation is stressful and should be performed with premedication. In the case of an INSURE (intubation/surfactant/extubation) procedure a short duration of action of the premedication used is needed to facilitate fast extubation. Given its pharmacological profile, remifentanil seems a suitable candidate. Objectives: The aim here was to evaluate the effect and side effects of remifentanil as a premedication for preterm neonates undergoing INSURE. Methods: A prospective, single-center study in a level III neonatal intensive care unit was conducted. The quality of sedation was assessed in preterm infants receiving remifentanil prior to intubation for the INSURE procedure. Intravenous remifentanil was administered quickly and followed by a saline flush in approximately 30 s. The quality of sedation was defined by a combination of adequate sedation score, good intubation conditions and absence of side effects. Results: The study was terminated after the inclusion of 14 patients because of the high rate of side effects and the poor intubation conditions. Adequate sedation was achieved in only 2 patients (14%). Six patients (43%) needed additional propofol to obtain adequate sedation. Chest wall rigidity occurred in 6 patients (43%). Conclusions: The rapid administration of remifentanil provides insufficient sedation and is associated with a high risk of chest wall rigidity in preterm neonates

Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different paracetamol doses in preterm infants are lacking. __Objectives:__ To determine the analgesic effects of different single intravenous paracetamol doses on pain from peripherally inserted central catheter (PICC) placement in preterm infants. __Methods:__ In a blinded randomized controlled trial, the an

Limited effects of intravenous paracetamol on patent ductus arteriosus in very low birth weight infants with contraindications for ibuprofen or after ibuprofen failure

Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3–7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 251/7 weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %. Conclusion: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective.What is known:• The ductus arteriosus fails to close after birth in 30 to 60 % of prematurely born neonates and is a significant cause of morbidity and mortality in these infants.• Paracetamol gained importance as an alternative drug in PDA closure.What is new:• Paracetamol for PDA closure after ibuprofen treatment failure was not effective in VLBW infants.• Effect of paracetamol on PDA closure was observed when given as primary treatment

Morphine in ventilated neonates: Its effects on arterial blood pressure

Objective: To study the effects of continuous morphine infusion on arterial blood pressure in ventilatedneonates. 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 intraventricularhaemorrhage, major congenital anomalies, neuromuscular blockers. Intervention: Arterial blood pressure was measured before the start and during the first 48 hours ofmasked infusion of drug (morphine/placebo; 100mg/kg+10mg/kg/h). Outcome measures: Arterial blood pressure and blood pressure variability. Results:There were no significant differences in overall mean arterial blood pressure between themorphine 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 placebogroup (47%) (p = 0.004), the use of volume expanders and vasopressor drugs was not significantlydifferent (morphine group, 44%; placebo group, 48%; p = 0.87), indicating the limited clinicalsignificance 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 haemorrhageshowed no differences in blood pressure (Mann-Whitney U test 1953; p = 0.14) or incidence ofhypotension (x2test 1.16; df 1; p = 0.28). Conclusions:Overall arterial blood pressure, use of inotropes, and blood pressure variability were notinfluenced by morphine infusion. Therefore the clinical impact of hypotension as a side effect of low dosemorphine treatment in neonates is negligible