Neuraxial Analgesia in Neonates and Infants

Walker, Suellen M.; Yaksh, Tony L.

doi:10.1213/ane.0b013e31826253f2

Cited by 90 publications

(36 citation statements)

References 309 publications

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“…29,30 With regard to concentration, clinicians typically measure intrathecal injections in terms of dose, but for local toxicity, both drug concentration and duration of exposure are considered to be of particular importance. 30,31 The therapeutic intrathecal oxytocin dose in dogs is unknown, but in rats, it is approximately 0.1-1.0 μg, 32 administered in a volume of 10 μL, or a concentration of 10-100 μg/μL.…”

Section: Discussionmentioning

confidence: 99%

Preclinical Toxicity Screening of Intrathecal Oxytocin in Rats and Dogs

et al. 2014

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Background Anatomic, physiologic, and behavioral studies in animals suggest that spinally released oxytocin should produce analgesia in humans and may also protect from chronic pain after injury. Here we report preclinical toxicity screening of oxytocin for intrathecal delivery. Methods Intrathecal oxytocin, 11 μg (6 IU) or vehicle, was injected intrathecally in 24 rats, followed by frequent behavioral assessment and histologic examination of spinal contents 2 or 14 days after injection. In 3 dogs, a range of intrathecal oxytocin doses (18-550 μg in 0.5 mL) was injected followed by physiologic, biochemical, and behavioral assessments. Ten dogs were then randomized to receive 5 daily injections of intrathecal oxytocin, 550 μg in 0.5 mL, or vehicle with similar assessments and, 2 days later, necropsy and histologic analysis. Results In rats intrathecal oxytocin resulted in transient scratching and itching behaviors, without other differences from vehicle. There was no behavioral, gross anatomic, or histologic evidence of neurotoxicity. Dose-ranging in dogs suggested mild effects on motor tone, blood pressure and heart rate at the 550 μg dose. Repeated boluses in dogs did not produce behavioral, biochemical, neurological, gross anatomic, or histologic evidence of neurotoxicity. Conclusions Substances, including natural neurotransmitters, may be toxic when administered in pharmacologic doses in the spinal cord. This preclinical toxicity screen in two species suggests that bolus injections of oxytocin in concentrations up to 1100 μg/mL is unlikely to cause neurotoxicity. They also support cautious clinical application of intrathecal oxytocin under regulatory supervision.

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Section: Discussionmentioning

confidence: 99%

Preclinical Toxicity Screening of Intrathecal Oxytocin in Rats and Dogs

et al. 2014

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“…Issues of such safety evaluations have been extensively discussed [243, 244, 462, 491]. Several specific guidelines will be outlined here.…”

Section: Current Spinal Agentsmentioning

confidence: 99%

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Yaksh

Fisher²,

Hockman³

et al. 2017

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Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety.

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“…However, it should be noted that subarachnoidally injected drugs are in close communication with neural tissue. Therefore, potential neurotoxicity should be considered before injecting any additive drugs (such as preservatives and antioxidants) into the cerebrospinal fluid [11,57]. The use of preservative-free additives seems to be a safe method that avoids these neurotoxic risks.…”

Section: Adjuncts To Local Anaesthetics In Paediatric Spinal Anaesthesiamentioning

confidence: 99%

Spinal Anaesthetic Management in Paediatric Surgery

Caliskan¹

2017

Pediatric and Neonatal Surgery

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The first paediatric cases involving the use of spinal anaesthesia were published at the end of the nineteenth century. However, the technique did not receive much interest in paediatric anaesthesia until the 1980s. In the last three decades, paediatric spinal anaesthesia has received widespread approval as an alternative technique to general anaesthesia in school-/preschool-aged children, particularly in term and preterm neonates with high risk associated with general anaesthesia. The development of new and safer local anaesthetics mainly through better understanding of the pharmacokinetics and dynamics and dedicated paediatric tools are the keys to this success. Paediatric spinal anaesthesia is an easy and effective technique, and its high efficiency and safety are supported by the presence of numerous publications from the medical literature. However, it remains limited to situations in which general anaesthesia poses a major risk. Despite these advances, it is important to understand the correct technique and the anatomy of children at different ages. Also, the appropriate equipment, the pharmacokinetics and toxicities of local anaesthetics and the indications and complications of paediatric regional blocks should be well known. The goal of this chapter is to review and discuss some of these topics of paediatric spinal anaesthesia for paediatric surgery.

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Neuraxial Analgesia in Neonates and Infants

Cited by 90 publications

References 309 publications

Preclinical Toxicity Screening of Intrathecal Oxytocin in Rats and Dogs

Preclinical Toxicity Screening of Intrathecal Oxytocin in Rats and Dogs

Current and Future Issues in the Development of Spinal Agents for the Management of Pain

Spinal Anaesthetic Management in Paediatric Surgery

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