Citations

This is the first clinical practice guideline (CPG) from the American Academy of Pediatrics outlining evidence-based approaches to safely prescribing opioids for acute pain in outpatient settings. The central goal is to aid clinicians in understanding when opioids may be indicated to treat acute pain in children and adolescents and how to minimize risks (including opioid use disorder, poisoning, and overdose). The document also seeks to alleviate disparate pain treatment of Black, Hispanic, and American Indian/Alaska Native children and adolescents, who receive pain management that is less adequate and less timely than that provided to white individuals. There may also be disparities in pain treatment based on language, socioeconomic status, geographic location, and other factors, which are discussed. The document recommends that clinicians treat acute pain using a multimodal approach that includes the appropriate use of nonpharmacologic therapies, nonopioid medications, and, when needed, opioid medications. Opioids should not be prescribed as monotherapy for children or adolescents who have acute pain. When using opioids for acute pain management, clinicians should prescribe immediate-release opioid formulations, start with the lowest age- and weight-appropriate doses, and provide an initial supply of 5 or fewer days, unless the pain is related to trauma or surgery with expected duration of pain longer than 5 days. Clinicians should not prescribe codeine or tramadol for patients younger than 12 years; adolescents 12 to 18 years of age who have obesity, obstructive sleep apnea, or severe lung disease; to treat postsurgical pain after tonsillectomy or adenoidectomy in patients younger than 18 years; or for any breastfeeding patient. The CPG recommends providing opioids when appropriate for treating acutely worsened pain in children and adolescents who have a history of chronic pain; clinicians should partner with other opioid-prescribing clinicians involved in the patient’s care and/or a specialist in chronic pain or palliative care to determine an appropriate treatment plan. Caution should be used when treating acute pain in those who are taking sedating medications. The CPG describes potential harms of discontinuing or rapidly tapering opioids in individuals who have been on stable, long-term opioids to treat chronic pain. The guideline also recommends providing naloxone and information on naloxone, safe storage and disposal of opioids, and direct observation of medication administration. Clinicians are encouraged to help caregivers develop a plan for safe disposal. The CPG contains 12 key action statements based on evidence from randomized controlled trials, high-quality observational studies, and, when studies are lacking or could not feasibly or ethically be conducted, from expert opinion. Each key action statement includes a level of evidence, the benefit-harm relationship, and the strength of recommendation.

Studies were performed in dogs to determine if inhibition of neuronal reuptake of norepinephrine was the cause of the enhanced response to sympathetic nerve impulses seen in the cutaneous veins when the temperature of the blood perfusing them was decreased. Changes in driving pressure of the saphenous vein perfused with blood at constant flow were used to measure venomotor responses. The increases in venoconstrictor response to norepinephrine infusion caused by cooling the perfusate were similar in both hindlegs, one subjected to acute and the other to chronic sympathectomy. Blocking the reentry of norepinephrine into the sympathetic nerve endings by treating the vein with cocaine did not affect the augmentation by local cooling of the constrictor response to norepinephrine or electric stimulation of the lumbar sympathetic chain. The venoconstrictor responses to norepinephrine, epinephrine, 5-hydroxytryptamine, and molar potassium chloride were all augmented by local cooling. The results suggest that the sensitizing effect of cold on the smooth muscle of the veins cannot be explained by inhibition of norepinephrine re-uptake by the nerve terminals.

The cutaneous veins of the dog constrict and dilate with local cooling and warming, respectively. This response, which is dependent on the integrity of the adrenergic nerves, might be explained by an altered response of the smooth muscle to a given frequency of sympathetic nerve impulses or by local temperature receptors that initiate alterations in sympathetic nerve activity. In the lateral saphenous vein perfused at 42°, 27°, and 17°C, the constriction caused by stimulation of lumbar sympathetic nerves was 40%, 160%, and 200%, respectively, of that at 37°C; the constriction caused by norepinephrine at the same temperatures was 70%, 187%, and 318% of that at 37°C. Division of the dorsal spinal roots from L-1 to S-1 made no difference to the veno-constrictor response to local cooling. It is concluded that an alteration in the sensitivity of the smooth muscle to arriving sympathetic nerve impulses accounts for the venous responses to local temperature changes seen in the intact dog.

To study the separate actions of peripheral and central temperature-sensitive systems on the cutaneous veins of the dog, a cross-circulation preparation was made in which hindleg and central temperatures could be varied independently. The lateral saphenous vein of a vascularly isolated hindleg was cross-perfused at constant flow; the difference between perfusion and femoral vein pressures was a measure of venomotor activity. With central temperature constant, local cooling of one leg from 47° to 17°C caused the lateral saphenous vein to constrict; sensitivity to cooling was maximal between 42° and 27°C. With leg temperature constant, central cooling caused the lateral saphenous vein to constrict; over the range of 40° to 33°C, the constriction was linearly related to the decrease in temperature. Central heating reduced the response to local cooling, whereas central cooling had the opposite effect. Thus a decrease in central temperature from 38° to 34°C increased the venoconstrictor response to local cooling from 42° to 22°C by a factor of ten or more.

The lateral saphenous vein of the dog was perfused with homologous blood at constant, flow. Changes in perfusion pressure were used to measure active changes in venous tone. Cooling of the perfusate caused the vein to constrict and warming to relax. Most of the change occurred over the temperature range of 27° to 42°C. The powerful venoconstrictor response to cooling depended on intact sympathetic nerves, since it was reduced by lumbar sympathectomy and largely abolished by alpha-receptor or ganglionic blockade. The response was confined to the vein being cooled. By comparison, cooling the body core when the temperature of the blood in the vein was 37°C caused a generalized constriction of the superficial limb veins. These responses were impaired by anesthetic agents (for example, pentobarbital), by generalized hypoxia, and by arterial hypotension. The data indicate a role for the cutaneous veins in temperature regulation. In the cold, the venous return is directed preferentially to the venae comitantes for heat preservation through countercurrent exchange with the arteries, and in warmth to the superficial veins for heat dissipation.