Moving Toward a Multimodal Analgesic Regimen for Acute Sickle Cell Pain with Non-Opioid Analgesic Adjuncts: A Narrative Review

Abstract

Purpose of Review Sickle cell disease (SCD) is an inherited hemoglobinopathy with potential life-threatening complications that affect millions of people worldwide. Severe and disabling acute pain, referred to as a vaso-occlusive crisis (VOC), is a fundamental symptom of the disease and the primary driver for acute care visits and hospitalizations. Despite the publication of guidelines for VOC management over the past decade, management of VOCs remains unsatisfactory for patients and providers. Recent Findings Acute SCD pain includes pain secondary to VOCs and other forms of acute pain. Distinguishing VOC from non-VOC pain may be challenging for both patients and clinicians. Further, although opioids have been the gold-standard for VOC pain management for decades, the current highest standard of care for all acute pain is a multimodal approach that is less dependent on opioids, and, instead incorporates analgesics and adjuvants from different mechanistic pathways. In this narrative review, we focus on a multimodal pharmacologic approach for acute SCD pain management and explore the evidence for existing non-opioid pharmacological adjuncts. Moreover, we present an explanatory model of pain, which is not only novel in its application to SCD pain but also captures the multidimensional nature of the SCD pain experience and supports the need for such a multimodal approach. This model also highlights opportunities for new investigative and therapeutic targets – both pharmacological and non-pharmacological. Summary Multimodal pain regimens that are less dependent on opioids are urgently needed to improve acute pain outcomes for individuals with SCD. The proposed explanatory model for SCD pain offers novel opportunities to improve acute pain management for SCD patients.

Safety and efficacy of ketorolac continuous infusion for multimodal analgesia of vaso-occlusive crisis in patients with sickle cell disease

“…The innovative aspects of SITE algorithm are the optimization of the triage and of the pain management with multimodal analgesia. This is based on the administration of drugs with different pharmacological mechanisms of action and maximizing analgesia and minimizing their adverse events [ 3 – 5 ]. Additionally, multimodal analgesia controls pain of different origin such as vascular or neuropathic pain that characterizes SCD [ 6 ] and decreases the opioid induced post-synaptic changes underlying tolerance and hyperalgesia [ 7 ], contributing to the reduction in the incidence of most severe SCD-related complications such as the acute chest syndrome [ 8 ].…”

Intraindividual pain variability metrics for youth with sickle cell disease: Relations to health outcomes

“…9 The implied intent, to conceptualize or define SCD pain phenotypes using summary pain measures 10,11 and then use them to predict pain-related outcomes or design treatment interventions, has met with only modest success based on recent reviews or treatment guidelines. 12,13 Describing SCD pain using these gross summary measures is simply not detailed enough to improve treatment, create better prognoses, or increase our understanding of mechanistic processes, information essential for guiding our intervention and prevention efforts. What is needed are better systems for describing and phenotyping SCD pain, an area of intense investigation.…”

“…They have then tried to relate either of these SCD pain measures or utilization due to VOC to health‐related quality of life, 7 daily mood and stress, 8 or coping 9 . The implied intent, to conceptualize or define SCD pain phenotypes using summary pain measures 10,11 and then use them to predict pain‐related outcomes or design treatment interventions, has met with only modest success based on recent reviews or treatment guidelines 12,13 . Describing SCD pain using these gross summary measures is simply not detailed enough to improve treatment, create better prognoses, or increase our understanding of mechanistic processes, information essential for guiding our intervention and prevention efforts.…”

Biopsychosocial Factors Associated With Pain and Pain-Related Outcomes in Adults and Children With Sickle Cell Disease: A Multivariable Analysis of the GRNDaD Multicenter Registry

“…The biopsychosocial model of pain emphasizes that pain is a complex, multidimensional phenomenon that is influenced by biological, psychological, and social mechanisms. 11 , 12 In a previous publication, we introduced an explanatory model for sickle cell pain 13 that is grounded in the neuromatrix framework proposed by pain psychologist, Ronald Melzack. 14 Consistent with the biopsychosocial model of pain, our explanatory model emphasizes the complex interplay between biological, psychological, and social factors in the perception and modulation of pain in SCD.…”