Manejo de la sedación y la analgesia en unidades de cuidados intensivos neonatales españolas

[Abstract] Introduction. Pain management and sedation is a priority in neonatal intensive care units. A study was designed with the aim of determining current clinical practice as regards sedation and analgesia in neonatal intensive care units in Spain, as well as to identify factors associated with the use of sedative and analgesic drugs. Methods. A multicenter, observational, longitudinal and prospective study. Results. Thirty neonatal units participated and included 468 neonates. Of these, 198 (42.3%) received sedatives or analgesics. A total of 19 different drugs were used during the study period, and the most used was fentanyl. Only fentanyl, midazolam, morphine and paracetamol were used in at least 20% of the neonates who received sedatives and/or analgesics. In infusions, 14 different drug prescriptions were used, with the most frequent being fentanyl and the combination of fentanyl and midazolam. The variables associated with receiving sedation and/or analgesia were, to have required invasive ventilation (p 3 (p = .023; OR = 2.26), the existence of pain evaluation guidelines in the unit (p < .001; OR = 3.82), and a pain leader (p = .034; OR = 2.35). Conclusions. Almost half of the neonates admitted to intensive care units receive sedatives or analgesics. There is significant variation between Spanish neonatal units as regards sedation and analgesia prescribing. Our results provide evidence on the “state of the art”, and could serve as the basis of preparing clinical practice guidelines at a national level.[Resumen] Introducción. El manejo del dolor y la sedación es una prioridad de los cuidados intensivos neonatales. Se diseñó un estudio con el objetivo de determinar la práctica clínica actual en relación con la sedación y la analgesia en unidades de cuidados intensivos neonatales en España e identificar factores asociados al uso de fármacos sedantes o analgésicos. Métodos. Estudio multicéntrico, observacional, longitudinal y prospectivo. Resultados. Participaron 30 unidades neonatales y se reclutó a 468 neonatos. De estos, 198 (42.3%) recibieron medicación sedante o analgésica. En total, se usaron durante el período de estudio 19 fármacos distintos, de los cuales el más utilizado fue el fentanilo. Solo fentanilo, midazolam, morfina y paracetamol se usaron al menos en un 20% de los neonatos que recibieron sedación y/o analgesia. Se usaron 14 pautas distintas de fármacos en perfusión, siendo las más frecuentes la infusión de fentanilo y la combinación de fentanilo y midazolam. Las variables asociadas a recibir sedación y/o analgesia fueron el haber precisado ventilación invasiva (p = 3 (p = 0.023; OR = 2.26), la existencia en la unidad de guías de evaluación del dolor (p < 0.001; OR = 3.82) y de un líder de dolor (p = 0.034; OR = 2.35). Conclusiones. Casi la mitad de los neonatos ingresados en cuidados intensivos recibe medicación sedante y/o analgésica. Existe una importante variabilidad entre las unidades neonatales españolas en relación con las pautas de sedación y analgesia. Nuestros resultados permiten conocer el “estado del arte” y pueden servir de base para la elaboración de guías de práctica clínica a nivel nacional

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

Age- and therapy-related effects on morphine requirements and plasma concentrations of morphine and its metabolites in postoperative infants

BACKGROUND: To investigate clinical variables such as gestational age, sex, weight, the therapeutic regimens used and mechanical ventilation that might affect morphine requirements and plasma concentrations of morphine and its metabolites. METHODS: In a double-blind study, neonates and infants stratified for age [group I 0-4 weeks (neonates), group II > or =4-26 weeks, group III > or =26-52 weeks, group IV > or =1-3 yr] admitted to the paediatric intensive care unit after abdominal or thoracic surgery received morphine 100 micro g kg(-1) after surgery, and were randomly assigned to either continuous morphine 10 micro g kg(-1) h(-1) or intermittent morphine boluses 30 micro g kg(-1) every 3 h. Pain was measured using the COMFORT behavioural scale and a visual analogue scale. Additional morphine was adm

Long-Term Behavioral Effects of Repetitive Pain in Neonatal Rat Pups

Human preterm neonates are subjected to repetitive pain during neonatal intensive care. We hypothesized that exposure to repetitive neonatal pain may cause permanent or long-term changes because of the developmental plasticity of the immature brain. Neonatal rat pups were stimulated one, two, or four times each day from P0 to P7 with either needle prick (noxious groups N1, N2, N4) or cotton tip rub (tactile groups T1, T2, T4). In groups N2, N4, T2, T4 stimuli were applied to separate paws at hourly intervals;each paw was stimulated only once a day. Identical rearing occurred from P7 to P22 days. Pain thresholds were measured on P16, P22, and P65 (hot-plate test), and testing for defensive withdrawal, alcohol preference, air-puff startle, and social discrimination tests occurred during adulthood. Adult rats were exposed to a hot plate at 62°C for 20 s, then sacrificed and perfused at 0 and 30 min after exposure. Fos expression in the somatosensory cortex was measured by immunocytochemistry. Weight gain in the N2 group was greater than the T2 group on P16 (p < 0.05) and P22 (p < 0.005); no differences occurred in the other groups. Decreased pain latencies were noted in the N4 group [5.0 ± 1.0 s vs. 6.2 ± 1.4 s on P16 (p < 0.05); 3.9 ± 0.5 s vs. 5.5 ± 1.6 s on P22 (p < 0.005)], indicating effects of repetitive neonatal pain on subsequent development of the pain system. As adults, N4 group rats showed an increased preference for alcohol (55 ± 18% vs. 32 ± 21%;p = 0.004); increased latency in exploratory and defensive withdrawal behavior (p < 0.05); and a prolonged chemosensory memory in the social discrimination test (p < 0.05). No significant differences occurred in corticosterone and ACTH levels following air-puff startle or in pain thresholds at P65 between N4 and T4 groups. Fos expression at 30 min after hot-plate exposure was significantly greater in all areas of the somatosensory cortex in the T4 group compared with the N4 group (p < 0.05), whereas no differences occurred just after exposure. These data suggest that repetitive pain in neonatal rat pups may lead to an altered development of the pain system associated with decreased pain thresholds during development. Increased plasticity of the neonatal brain may allow these and other changes in brain development to increase their vulnerability to stress disorders and anxiety-mediated adult behavior. Similar behavioral changes have been observed during the later childhood of expreterm neonates who were exposed to prolonged periods of neonatal intensive care

Multiple intravenous doses of paracetamol result in a predictable pharmacokinetic profile in very preterm infants

AimThe therapeutic options available to treat neonatal pain are limited, and one alternative for nonopioid systemic treatment is paracetamol. However, pharmacokinetic data from prolonged administration of intravenous paracetamol in neonates are limited. The aim of this study was to present pharmacokinetics after multiple dose of intravenous paracetamol in very preterm infants of <32weeks' gestation. MethodsFifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites. ResultsA two-compartment pharmacokinetic model gave the best fit for all individual patients and resulted in a predictable pharmacokinetic profile. The estimated pharmacokinetic population parameters were volume of distribution 0.7640.225L/kg, elimination rate constant (k(e)) 0.117 +/- 0.091/h and intercompartment rate constants k(12) 0.607 +/- 0.734/h and k(21) 1.105 +/- 0.762/h. ConclusionOur study found that multiple doses of intravenous paracetamol resulted in a predictable pharmacokinetic profile in very preterm infants. Increases in postmenstrual age and weight were associated with increased clearance. No evidence of hepatotoxicity was found