Barriers to Pediatric Pain Management in Children Undergoing Surgery: A Survey of Health Care Providers

The appropriate pain management in neonates and children is lacking. Factors that prevent the execution of proper pain relief vary from center to center. We studied the factors responsible for it in a surgical unit. We conducted a survey at a tertiary-level institute among the resident doctors and nursing staff by means of an informal questionnaire analyzing their basic knowledge. The questions pertained mainly to pain assessment, analgesic usage, role of opioids, and formal training, and the responses so obtained were analyzed under these four headings. Seventy-three percent (22/30) of the residents and 74% (26/35) of the nursing staff knew about pain assessment scoring system in pediatric patients. However, assessment of pain in emergency cases was always done by only 6.6% of the residents. Effect of analgesia on severity of pain was never recorded by 33% (10/30) of the residents. Eighty-six percent (26/30) of the residents and 91% (32/35) of the nursing staff had adequate knowledge about analgesic dosage and interval for routine use. Ten of the 30 (33%) residents believed that analgesic administration in an acute abdomen, before definitive diagnosis, will always mask the symptoms. During a minor procedure, 56% (17/30) of the residents always used analgesia. Only 3.3% (1/30) of residents and 2.8% (1/35) of the nursing staff had received a structured training for pain management. Although, 93% (28/30) of the residents claimed to know about the safety of use of opioids, only 46% (14/30) used them routinely as analgesics. Pain management in surgical neonates and children is often ignored. Lack of formal training, inadequate knowledge, and standard protocols are the barriers in our setup, which may in turn be due to overwhelming attention given to the surgical condition.     

Management of Severe Pain Due to Lumbar Disk Protrusion

Lumbar intervertebral disk protrusion can cause excruciating pain in severe cases, which can be exacerbated by activity such as sitting down and straining at stool. Acute sciatica due to disk rupture will improve within 1 to 3 months. The efficacy of drugs used for the management of sciatica in primary care is unclear. Severe cases can require opioid analgesia, however people taking opioids for pain relief frequently present with opioid-induced bowel dysfunction. The use of transforaminal steroid injections is a controversial issue and repeat steroid injections should be considered in light of the risk–benefit profile of the individual patient.

This report is adapted from paineurope 2014; Issue 3, ©Haymarket Medical Publications Ltd, and is presented with permission. paineurope is provided as a service to pain management by Mundipharma International, LTD and is distributed free of charge to healthcare professionals in Europe. Archival issues can be accessed via the website: http://www.paineurope.com at which European health professionals can register online to receive copies of the quarterly publication.     

Neuropeptides: Metabolism to Bioactive Fragments and the Pharmacology of Their Receptors

The proteolytic processing of neuropeptides has an important regulatory function and the peptide fragments resulting from the enzymatic degradation often exert essential physiological roles. The proteolytic processing generates, not only biologically inactive fragments, but also bioactive fragments that modulate or even counteract the response of their parent peptides. Frequently, these peptide fragments interact with receptors that are not recognized by the parent peptides. This review discusses tachykinins, opioid peptides, angiotensins, bradykinins, and neuropeptide Y that are present in the central nervous system and their processing to bioactive degradation products. These well‐known neuropeptide systems have been selected since they provide illustrative examples that proteolytic degradation of parent peptides can lead to bioactive metabolites with different biological activities as compared to their parent peptides. For example, substance P, dynorphin A, angiotensin I and II, bradykinin, and neuropeptide Y are all degraded to bioactive fragments with pharmacological profiles that differ considerably from those of the parent peptides. The review discusses a selection of the large number of drug‐like molecules that act as agonists or antagonists at receptors of neuropeptides. It focuses in particular on the efforts to identify selective drug‐like agonists and antagonists mimicking the effects of the endogenous peptide fragments formed. As exemplified in this review, many common neuropeptides are degraded to a variety of smaller fragments but many of the fragments generated have not yet been examined in detail with regard to their potential biological activities. Since these bioactive fragments contain a small number of amino acid residues, they provide an ideal starting point for the development of drug‐like substances with ability to mimic the effects of the degradation products. Thus, these substances could provide a rich source of new pharmaceuticals. However, as discussed herein relatively few examples have so far been disclosed of successful attempts to create bioavailable, drug‐like agonists or antagonists, starting from the structure of endogenous peptide fragments and applying procedures relying on stepwise manipulations and simplifications of the peptide structures.     

Maternal hair cortisol levels as a novel predictor of neonatal abstinence syndrome severity: A pilot feasibility study

Neonatal abstinence syndrome (NAS) after in-utero opioid exposure remains a poorly understood condition with multiple factors contributing to severity. Exposure to maternal stress may be one contributing factor. Hair cortisol measurement represents a novel technique for assessing prenatal stress. In this pilot study, the association between maternal hair cortisol levels and NAS severity was examined in 70 postpartum women with opioid use disorder within 72 hr of delivery. Infants were monitored for NAS and treated according to institutional protocol. Forty-four (63%) of the infants were pharmacologically treated for NAS, with a mean length of hospital stay (LOS) for all infants of 14.2 (SD 9.0) days. The mean cortisol level in the mothers was 131.8 pg/mg (SD 124.7). In bivariate analysis, higher maternal hair cortisol levels were associated with shorter infant LOS (R = −.26, p = .03) and fewer infant opioid treatment days (R = −.28, p = .02). Results were no longer statistically significant in regression models after adjusting for maternal opioid and smoking. In conclusion, we demonstrated the feasibility of hair cortisol assaying within the first few days after delivery in mothers with opioid use disorder as a novel marker for NAS. The findings suggest that maternal stress may impact the severity of infant opioid withdrawal.     

Direct‐acting antiviral interactions with opioids,alcohol or illicit drugs of abuse in HCV‐infected patients

The hepatitis C virus (HCV) prevalence is extremely high in patients who consume and inject illicit drugs. Concerns about poor adherence and fear of interaction with drugs of abuse could constitute further disincentive for treatment initiation in these patients. We discussed the pharmacokinetics (PKs) and pharmacodynamics (PD) of currently prescribed direct antiviral agents (NSA5 inhibitors: daclatasvir, elbasvir, ledipasvir, pibrentasvir, velpatasvir; NS5B inhibitor: sofosbuvir; NS3/4A protease inhibitors: glecaprevir, grazoprevir, voxilaprevir) and most common substances of abuse (opioids: buprenorphine, fentanyl, heroin, methadone, morphine, oxycodone; stimulants: amphetamines, cathinones, cocaine; cannabinoids; ethanol). Overall, most direct‐acting antivirals (DAAs) are substrates and inhibitors of the transmembrane transporter P‐glycoprotein (P‐gp), and several of them are metabolized by cytochrome P450 enzymes. Clinically relevant interactions are associated with P‐gp and CYP3A modulators. Most substances of abuse are eliminated by Phase I and Phase II metabolizing enzymes, but none of them are either major inhibitors or inducers. PK studies did not show any relevant interactions between DAA and methadone or buprenorphine. Based on pharmacological considerations, neither efficacy loss nor adverse drug event associated with detrimental interaction are expected with opioids, stimulants, cannabinoids and ethanol. In summary, our literature review shows that the interaction potential of DAA with most opioids and illicit drugs is limited and should not be a hurdle to the initiate DAA.     

In vitro metabolism of the novel synthetic opioid agonist cyclopropylfentanyl and subsequent confirmation in authentic human samples using liquid chromatography‐high resolution mass spectrometry

Novel synthetic opioids (NSOs) are a class of novel psychoactive substances (NPS) that are growing in popularity and presenting a significant public health risk. Included in this class are derivatives of the highly potent analgesic, fentanyl. Cyclopropylfentanyl (CycP‐F) was first reported to the EU Early Warning System in August 2017, and was subsequently linked to more than 100 deaths in the US alone. Limited pharmacological, pharmacokinetic or toxicological data is available for many emerging NSOs; however we can expect novel fentanyl analogues to present limited detection windows, short onset, narrow therapeutic indices and the potential for very high potency. Knowledge of the metabolism of these drugs is essential for the identification of analytical targets for their detection. Therefore in vitro metabolites of CycP‐F were produced using human liver microsomal incubations. Metabolites formed were elucidated using liquid chromatography‐high resolution accurate mass analysis (LC‐HRAM). Identified metabolites were added to our accurate mass screening database for NPS which was utilised for subsequent screening analysis. CycP‐F and metabolites were identified in two human blood case samples. Eleven metabolites were identified in vitro, with the major metabolites produced via N‐dealkylation, monohydroxylation and N‐oxidation. Analysis of the positive case samples identified four in vivo metabolites, all of which were observed in vitro. The major metabolite identified in vitro and in vivo was the N‐dealkylated nor‐metabolite; two further mono‐hydroxylated and one dihydroxylated metabolite were detected in vivo.