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.     

Peat smoke inhalation alters blood pressure,baroreflex sensitivity,and cardiac arrhythmia risk in rats

ABSTRACT

Wildland fires (WF) are linked to adverse health impacts related to poor air quality. The cardiovascular impacts of emissions from specific biomass sources are however unknown. The purpose of this study was to assess the cardiovascular impacts of a single exposure to peat smoke, a key regional WF air pollution source, and relate these to baroreceptor sensitivity and inflammation. Three-month-old male Wistar-Kyoto rats, implanted with radiotelemeters for continuous monitoring of heart rate (HR), blood pressure (BP), and spontaneous baroreflex sensitivity (BRS), were exposed once, for 1-hr, to filtered air or low (0.38 mg/m³ PM) or high (4.04 mg/m³) concentrations of peat smoke. Systemic markers of inflammation and sensitivity to aconitine-induced cardiac arrhythmias, a measure of latent myocardial vulnerability, were assessed in separate cohorts of rats 24 hr after exposure. PM size (low peat = 0.4–0.5 microns vs. high peat = 0.8–1.2 microns) and proportion of organic carbon (low peat = 77% vs. high peat = 65%) varied with exposure level. Exposure to high peat and to a lesser extent low peat increased systolic and diastolic BP relative to filtered air. In contrast, only exposure to low peat elevated BRS and aconitine-induced arrhythmogenesis relative to filtered air and increased circulating levels of low-density lipoprotein cholesterol, complement components C3 and C4, angiotensin-converting enzyme (ACE), and white blood cells. Taken together, exposure to peat smoke produced overt and latent cardiovascular consequences that were likely influenced by physicochemical characteristics of the smoke and associated adaptive homeostatic mechanisms.     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.