Articles: opioid-analgesics.
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Cochrane Db Syst Rev · Apr 2023
Review Meta AnalysisSystemic opioid regimens for postoperative pain in neonates.
Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature. ⋯ In this review, we included seven randomized controlled clinical trials (504 infants) from 1996 to 2020. We identified no studies comparing different doses of the same opioid, or different routes. The administration of continuous opioid infusion versus bolus administration of opioids was evaluated in six studies, while one study compared 'as needed' versus 'as scheduled' administration of morphine given by parents or nurses. Overall, the effectiveness of continuous infusion of opioids over bolus infusion as measured by the visual analog scale (MD 0.00, 95% confidence interval (CI) -0.23 to 0.23; 133 participants, 2 studies; I² = 0); or using the COMFORT scale (MD -0.07, 95% CI -0.89 to 0.75; 133 participants, 2 studies; I² = 0), remains unclear due to study designs' limitations, such as the unclear risk of attrition, reporting bias, and imprecision among reported results (very low certainty of the evidence). None of the included studies reported data on other clinically important outcomes such as all-cause mortality rate during hospitalization, major neurodevelopmental disability, the incidence of severe retinopathy of prematurity or intraventricular hemorrhage, and cognitive- and educational-related outcomes. AUTHORS' CONCLUSIONS: Limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. We are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. Only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.
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Neonates are an extremely vulnerable patient population, with 6% to 9% admitted to the neonatal intensive care unit (NICU) following birth. Neonates admitted to the NICU will undergo multiple painful procedures per day throughout their stay. There is increasing evidence that frequent and repetitive exposure to painful stimuli is associated with poorer outcomes later in life. To date, a wide variety of pain control mechanisms have been developed and implemented to address procedural pain in neonates. This review focused on non-opioid analgesics, specifically non-steroidal anti-inflammatory drugs (NSAIDs) and N-methyl-D-aspartate (NMDA) receptor antagonists, which alleviate pain through inhibiting cellular pathways to achieve analgesia. The analgesics considered in this review show potential for pain relief in clinical practice; however, an evidence summation compiling the individual drugs they comprise and outlining the benefits and harms of their administration is lacking. We therefore sought to summarize the evidence on the level of pain experienced by neonates both during and following procedures; relevant drug-related adverse events, namely episodes of apnea, desaturation, bradycardia, and hypotension; and the effects of combinations of drugs. As the field of neonatal procedural pain management is constantly evolving, this review aimed to ascertain the scope of non-opioid analgesics for neonatal procedural pain to provide an overview of the options available to better inform evidence-based clinical practice. OBJECTIVES: To determine the effects of non-opioid analgesics in neonates (term or preterm) exposed to procedural pain compared to placebo or no drug, non-pharmacological intervention, other analgesics, or different routes of administration. ⋯ We included two RCTs involving a total of 269 neonates conducted in Nigeria and India. NMDA receptor antagonists versus no treatment, placebo, oral sweet solution, or non-pharmacological intervention One RCT evaluated using oral ketamine (10 mg/kg body weight) versus sugar syrup (66.7% w/w at 1 mL/kg body weight) for neonatal circumcision. The evidence is very uncertain about the effect of ketamine on pain score during the procedure, assessed with the Neonatal Infant Pain Scale (NIPS), compared with placebo (mean difference (MD) -0.95, 95% confidence interval (CI) -1.32 to -0.58; 1 RCT; 145 participants; very low-certainty evidence). No other outcomes of interest were reported on. Head-to-head comparison of different analgesics One RCT evaluated using intravenous fentanyl versus intravenous ketamine during laser photocoagulation for retinopathy of prematurity. Neonates receiving ketamine followed an initial regimen (0.5 mg/kg bolus 1 minute before procedure) or a revised regimen (additional intermittent bolus doses of 0.5 mg/kg every 10 minutes up to a maximum of 2 mg/kg), while those receiving fentanyl followed either an initial regimen (2 μg/kg over 5 minutes, 15 minutes before the procedure, followed by 1 μg/kg/hour as a continuous infusion) or a revised regimen (titration of 0.5 μg/kg/hour every 15 minutes to a maximum of 3 μg/kg/hour). The evidence is very uncertain about the effect of ketamine compared with fentanyl on pain score assessed with the Premature Infant Pain Profile-Revised (PIPP-R) scores during the procedure (MD 0.98, 95% CI 0.75 to 1.20; 1 RCT; 124 participants; very low-certainty evidence); on episodes of apnea occurring during the procedure (risk ratio (RR) 0.31, 95% CI 0.08 to 1.18; risk difference (RD) -0.09, 95% CI -0.19 to 0.00; 1 study; 124 infants; very low-certainty evidence); and on hypotension requiring medical therapy occurring during the procedure (RR 5.53, 95% CI 0.27 to 112.30; RD 0.03, 95% CI -0.03 to 0.10; 1 study; 124 infants; very low-certainty evidence). The included study did not report pain score assessed up to 10 minutes after the procedure or episodes of bradycardia occurring during the procedure. We did not identify any studies comparing NSAIDs versus no treatment, placebo, oral sweet solution, or non-pharmacological intervention or different routes of administration of the same analgesics. We identified three studies awaiting classification. AUTHORS' CONCLUSIONS: The two small included studies comparing ketamine versus either placebo or fentanyl, with very low-certainty evidence, rendered us unable to draw meaningful conclusions. The evidence is very uncertain about the effect of ketamine on pain score during the procedure compared with placebo or fentanyl. We found no evidence on NSAIDs or studies comparing different routes of administration. Future research should prioritize large studies evaluating non-opioid analgesics in this population. As the studies included in this review suggest potential positive effects of ketamine administration, studies evaluating ketamine are of interest. Furthermore, as we identified no studies on NSAIDs, which are widely used in older infants, or comparing different routes of administration, such studies should be a priority going forward.
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Limited studies are available on patients' perspectives regarding opioid-related awareness, beliefs, and pain management in primary care settings in the US. Pain catastrophizing (PC) is a cascade of negative thoughts and emotions in response to actual or anticipated pain. High PC is 1 of the strongest predictors of negative pain outcomes. ⋯ Significant gaps existed among our participants with high PC in their awareness of opioid epidemic issues and side effects/risks compared with their low PC counterparts. They may also carry positive beliefs regarding opioids and pain-control in general. In any pain care, it seems important to identify patients with high pain catastrophizing. Doing so may facilitates exploration of their beliefs and expectations regarding pain management and aids in tailoring individualized treatment and prevent adverse side effects.