Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Risk Factors for Chronic Opioid Use Following Hip and Knee Arthroplasty: Evidence from New Zealand Population Data

BackgroundPatients awaiting total joint arthroplasty (TJA) have high rates of opioid use, and many continue to use opioid medications long term after surgery. The objective of this study is to estimate the risk factors associated with chronic opioid use after TJA in a comprehensive population-based cohort.MethodsAll patients undergoing TJA in the New Zealand public healthcare system were identified from Ministry of Health records. Dispensing of opioid medications up to 3 years postsurgery and potential risk factors, including demographic, socioeconomic, and surgery-related characteristics, pre-existing medical comorbidities, and use of other analgesic medications prior to surgery, were identified from linked population databases. Logistic regression analysis was used to identify factors associated with chronic postoperative opioid use.ResultsThe strongest risk factor for chronic postoperative opioid use was preoperative opioid use. Other significant risk factors included perioperative opioid use, history of alcohol or drug abuse, younger age, female gender, knee arthroplasty, several comorbid health conditions, and preoperative use of some analgesic medications. Protective factors included higher education levels and preoperative use of nonsteroidal anti-inflammatory drugs. Most risk factors had similar effects on chronic postoperative opioid use irrespective of the length of follow-up considered (1, 2, or 3 years).ConclusionThis study of a comprehensive nationwide population-based cohort of TJA patients with 3 years of follow-up identified several modifiable risk factors and other easily measured patient characteristics associated with higher risk of long-term postoperative opioid use.     

Long QT interval syndrome with increased QT dispersion

This case report describes the anaesthetic management of a patient with sporadic-type long QT interval syndrome (LQTS), and increased QT dispersion, who presented for removal of an ovarian cyst. Beta adrenergic blockade and adequate depth of anaesthesia for successful management is emphasized. The Successful use of epidural administration of lignocaine and opioids in addition to general anaesthesia is described.     

Modification of the Phe3 aromatic moiety in delta receptor-selective dermorphin/deltorphin-related tetrapeptides Effects on opioid receptor binding

The previously described cyclic delta opioid receptor-selective tetrapeptide H-Tyr-d -Cys-Phe-d -Pen-OH (JOM-13) was modified at residue 3 by incorporation of both natural and unnatural amino acids with varying steric, electronic, and lipophilic properties. Effects on mu and delta opioid receptor binding affinities were evaluated by testing the compounds for displacement of radiolabeled receptor-selective ligands in a guinea pig brain receptor binding assay. Results obtained with the bulky aromatic 1-Nal³ and 2-Nal³ substitutions suggest that the shape of the receptor subsite with which the side chain of the internal aromatic residue interacts differs for delta and mu receptors. This subsite of either receptor can accommodate the transverse steric bulk of the 1-Nal³ side chain but only the delta receptor can readily accept the more elongated 2-Nal³ side chain. Several analogs with pi-excessive heteroaromatic side chains in residue 3 were examined. In general, these analogs display diminished binding to mu and delta receptors, consistent with previous findings for analogs with residue 3 substitutions of modified electronic character. Several analogs with alkyl side chains in residue 3 were also examined. While delta receptor binding affinity is severely diminished with Val³, Ile³, and Leu³ substitutions, Cha³ substitution is very well tolerated, indicating that, contrary to the widely held belief, an aromatic side chain in this portion of the ligand is not required for delta receptor binding. Where possible, comparison of results in this delta-selective tetrapeptide series with those reported for analogous modification in the cyclic delta-selective pentapeptide [d -Pen², d -Pen⁵]enkephalin (DPDPE) and linear pentapeptide enkephalins reveals similar trends.     

Noradrenaline- and Enkephalin-Induced Inhibition of Voltage-Sensitive Calcium Currents in NG108-15 Hybrid Cells

Voltage-sensitive calcium currents were recorded from chemically differentiated neuroblastoma x glioma hybrid (NG108-15) cells using the whole-cell clamp technique. Both noradrenaline and [D-Ala2, D-Leu5] enkephalin (DADLE) reversibly depressed the amplitude of the calcium current by up to 30%. The response to noradrenaline occluded that to DADLE suggesting that both agonists depress the same fraction of current. The response to DADLE but not that to noradrenaline desensitized rapidly. Cells responded normally to noradrenaline when desensitized to the opioid. Responses to either agonist were absent in cells pre-incubated with pertussis toxin. In addition the response to noradrenaline became irreversible in cells dialysed internally with a non-hydrolysable analogue of GTP. The response to noradrenaline was not affected by treatment of the cells with either membrane-permeable analogues of cAMP or a combination of forskolin and isobutylmethylxanthine. It is concluded that both noradrenaline and DADLE depress the same fraction of voltage-dependent calcium current in NG108-15 cells; that the responses are mediated by a pertussis-sensitive GTP-binding protein but are not secondary to a reduction in the intracellular concentration of cAMP; and that desensitization of the opioid response occurs at a site linked intimately to the opioid receptor rather than at a common site in the transduction pathway between receptor activation and reduction in the calcium channel current.     

Effects of epidural bupivacaine and epidural morphine on bowel function and pain after hysterectomy

A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy. The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces. Twenty-two patients were randomly allocated to two equal groups. An "epidural morphine" group received general anesthesia and epidural morphine for postoperative pain relief, and an "epidural bupivacaine" group was given combined general anesthesia and epidural anesthesia with 0.5% bupivacaine intraoperatively and epidural analgesia with 0.25% bupivacaine postoperatively. Epidural morphine or bupivacaine was given for 42 h postoperatively. Pain intensity (visual analog scale) was low in both groups, but lower (P less than 0.05) in the epidural bupivacaine group. The time to first passage of flatus was 22 +/- 16 h in the epidural bupivacaine group and 56 +/- 22 h in the epidural morphine group (P less than 0.001). The time to first postoperative passage of feces was shorter (P less than 0.05) in the former than in the latter 57 +/- 44 h vs 92 +/- 22 h). The patients of the epidural bupivacaine group started intake of oral fluids earlier (P less than 0.01) and to a greater extent (P less than 0.05) than those in the epidural morphine group. It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine.