Ketamine for procedural pain relief in newborn infants

Abstract

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 ineVective method of relieving the pain caused by endotracheal suction. (Arch Dis Child Fetal Neonatal Ed 2001;85:F53-F56)

l-Carnitine rescues ketamine-induced attenuated heart rate and MAPK (ERK) activity in zebrafish embryos

“…In new born infants, ketamine at a dose of 2 mg/kg significantly reduces heart rate compared to the pacebo [52]. The zebrafish embryo response to ketamine with regard to heart rate is concordant with that of the human infants [52] and non-human primate PND5 and 35 infants [19]. Differential effects of ketamine on heart rate in new born and adult humans has been attributed to the poorly developed sarcoplasmic reticulum of the neonatal myocardium [53], which appears to be more dependent on the entry of extracellular calcium rather than the release of calcium from intracellular sarcoplasmic reticulum [54].…”

“…For example in Leghorn hens ketamine decreased heart rate at a relatively low dose [49]; in rabbits ketamine exposure caused a "slow normal" heart rate [50] and in rats, it stimulated cardiovascular function [51]. In new born infants, ketamine at a dose of 2 mg/kg significantly reduces heart rate compared to the pacebo [52]. The zebrafish embryo response to ketamine with regard to heart rate is concordant with that of the human infants [52] and non-human primate PND5 and 35 infants [19].…”

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

“…Conflicting results have been reported in the use of morphine for procedures such as heel lance (165,166) or tracheal suctioning (112,115). During tracheal suctioning, alfentanil was found to be effective but induced frequent thoracic rigidity (167), whereas ketamine was found to be inappropriate (125). For percutaneous central venous catheter (PCVC) placement, morphine provided good analgesia but induced mild respiratory depression (168).…”

“…Remifentanil decreased pain for PICC insertion (169) Thoracic rigidity requiring muscle blocker injection (alfentanil 20 g/kg) (167). Same time to complete the maneuver and procedure time as placebo (169) Acetaminophen Ն37 wks GA No effect for heel lance (170) Good hepatic tolerance (149) Ketamine Ineffective for tracheal suctioning (125) No cerebral hemodynamic adverse effect (5 mg/kg) (124) Repetitive painful stimuli may persistently alter pain processing in humans (171), and epidemiologic studies have revealed an association between peri-and neonatal complications and behavioral/emotional problems in childhood, anxiety/ depression, and even suicidal tendencies (172,173). Conversely, drug toxicity should not be underestimated and risk/ benefit balance must be evaluated when prescribing analgesia or sedation for neonates.…”

Prevention and Management of Pain in the Neonate: An Update

“…24 Ketamine hydrochloride was evaluated in a randomized, controlled trial for relief of procedural pain associated with endotracheal suctioning in ventilated preterm neonates. 101 However, these authors concluded that ketamine was only modestly effective at reducing pain scores and did not alter physiologic responses in heart rate and systemic blood pressure.…”