Ketamine for procedural pain relief in newborn infants.

AIM: To assess the suitability of ketamine for relief of pain caused by tracheal suction during ventilator treatment in newborn infants. STUDY DESIGN: In a randomised, double blind, cross over trial, 16 newborn infants received placebo or 0.5, 1, or 2 mg/kg ketamine as two minute infusions in random order five minutes before four separate endotracheal suctions, with intervals of at least 12 hours. RESULTS: Mean (SD) plasma ketamine concentration increased linearly with the dose (103 (49), 189 (75), and 379 (97) ng/ml after 0.5, 1, and 2 mg/kg respectively). Heart rate decreased significantly only after 2 mg/kg ketamine (-7 (10) beats/min, p = 0.029 v placebo). The increases in heart rate, arterial blood pressure, and pain score in response to tracheal suction during the placebo phase (11 (23) beats/min, p = 0.065; 6 (7) mm Hg, p = 0.004; 3.5 (interquartile range (IQR) 2.75-5) points, p = 0.001) were not attenuated by 0.5 or 2 mg/kg ketamine. However, 1 mg/kg ketamine attenuated the increase in pain score (1 (IQR 0.75-4.25) points, p = 0.043 v placebo), but not in heart rate (7 (23) beats/min) or blood pressure (7 (9) mm Hg). CONCLUSION: None of the doses of ketamine attenuated the changes in heart rate or blood pressure caused by suction, and only with a dose of 1 mg/kg was the suction induced pain moderately reduced. Thus infusion of ketamine at the doses used appears to be an ineffective method of relieving the pain caused by endotracheal suction.

Morphine clearance and effects in newborn infants in relation to gestational age.

OBJECTIVE: We sought to provide a rational basis for morphine administration in preterm infants in the immediate postnatal period by determining the clearance and evaluating the efficacy and adverse effects of a continuous infusion. STUDY DESIGN: Morphine was infused for 2 to 4 days (140 microg/kg over 1 hour followed by 20 microg/kg/h) to 31 ventilator-treated newborn infants (gestational age, 24 to 41 weeks; birth weight, 765 to 4,015 g). Morphine, morphine-3-glucuronide, and morphine-6-glucuronide concentrations in serum were determined from arterial blood obtained at 2, 12, 24, 48, and 60 hours after the start of morphine infusion at a median postnatal age of 10 hours. RESULTS: The mean +/- SD steady-state morphine concentration, 167 +/- 77 ng/mL, was achieved between 24 and 48 hours of infusion, and morphine-6-glucuronide and morphine-3-glucuronide concentrations did not reach steady state within 60 hours. Morphine clearance (range, 0.8 to 6.5 mL/min/kg) correlated significantly with gestational age (r = 0.60; P < .01) and birth weight (r = 0.55; P < .01). Pain relief did not correlate with the steady-state morphine concentration. However, significantly higher morphine concentrations were found in infants with decreased gastrointestinal motility (187 +/- 82 ng/mL) compared with those without (128 +/- 51 ng/mL; P < .05). CONCLUSIONS: Morphine should be used with caution in prematurely born infants because of its low clearance, which correlates with gestational age.

Gestational age and birth weight effects on plasma clearance of fentanyl in newborn infants.

OBJECTIVE: To provide a rational basis for the dosage of fentanyl in newborn infants by determining clearance in the first days of life. STUDY DESIGN: A continuous infusion of fentanyl for 2 to 3 days (10. 5 microg/kg over a 1-hour period followed by 1.5 microg/kg/h) was administered to 38 newborn infants who had undergone ventilation (gestational ages 26 to 42 weeks and birth weights 835 to 3550 g). Fentanyl concentrations were measured in arterial blood samples collected at 2, 12, 24, 48, and 60 hours after the start of fentanyl infusion. Fentanyl levels were correlated with a pain score. RESULTS: The mean (+/-SD) steady-state fentanyl concentration of 2.5 (+/-1) ng/mL achieved between 24 and 48 hours of infusion correlated significantly with the concomitant pain score (r = -0.57, P <.01). The clearance, 11.5 (+/-4.0) mL/min/kg, correlated significantly with the gestational age (r = 0.46, P <.01) and birth weight (r = 0. 48, P <.01). CONCLUSIONS: Because plasma fentanyl clearance increases with maturity, gestational age should be taken into account when fentanyl is administered to newborn infants.

Advantages of fentanyl over morphine in analgesia for ventilated newborn infants after birth: A randomized trial.

OBJECTIVE: To compare the efficacy and adverse effects of fentanyl or morphine analgesia during the first 2 days of life in newborn infants who underwent mechanical ventilation. STUDY DESIGN: In a randomized double-blind trial, 163 infants were allocated to receive a continuous infusion of fentanyl (10.5 microg/kg over a 1-hour period followed by 1.5 microg/kg/hr) or morphine (140 microg/kg over a 1-hour period followed by 20 microg/kg/hr) for at least 24 hours. The severity of pain was assessed with physiological parameters, a behavioral pain scale, and stress hormone concentrations before and 2 and 24 hours after the start of treatment. RESULTS: The analgesic effect was similar in both groups, as judged by the pain scale. Plasma adrenaline and noradrenaline concentrations decreased significantly from 0 to 24 hours in both groups. Median adrenaline decrease was 0.5 nmol/L (interquartile range [IQR] 1.1;0.0) in the fentanyl and 0.7 nmol/L (IQR 1.3;0.1) in the morphine group, noradrenaline 2.1 nmol/L (IQR 9.0;0.2), and 3.0 nmol/L (IQR 7. 5;0.3), respectively. beta-endorphin decreased significantly only in the fentanyl group ( 14 pmol/L (IQR 28; 7), P <.05). Decreased gastrointestinal motility was less frequent in the fentanyl group (23% vs 47%, P <.01). CONCLUSIONS: With at least as effective analgesia as with morphine, fentanyl had fewer side effects. Fentanyl may be superior to morphine for short-term postnatal analgesia in newborn infants.

Alfentanil as procedural pain relief in newborn infants.

AIMS: To assess the need for, and the suitability of, alfentanil for pain relief during tracheal suction used in assisted ventilation in newborn infants. METHODS: In a randomised, controlled, double blind, crossover trial, placebo (10 micrograms/kg) and 20 micrograms/kg alfentanil were infused in random order two minutes before three separate endotracheal suctions, at least six hours apart, to 10 infants. Measurements were made of physiological variables, behaviour, and stress hormones. RESULTS: After placebo infusion heart rate significantly increased (median 14; interquartile range 12-16 beats/minute) as did behavioural pain score (5; 3-5). Alfentanil (20 micrograms/kg) attenuated the heart rate increase, normalised the pain score, and caused a decrease in plasma adrenaline activity (0.3; 0.2-0.7 nmol/l). Noradrenaline concentration showed a nonsignificant decreasing trend with increasing alfentanil dose and beta endorphin was unchanged. Rigidity was noted in the placebo (n = 2), 10 micrograms/kg (n = 2), and 20 micrograms/kg (n = 5) alfentanil groups, respectively. CONCLUSIONS: Tracheal suction is a painful procedure. The dose of alfentanil required for pain relief (20 micrograms/kg) causes a high incidence of rigidity and thus should be used only with muscle relaxant.